ORCID Profile
0000-0003-0295-4214
Current Organisation
Deakin University
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Publisher: Informa UK Limited
Date: 25-11-2019
DOI: 10.1080/01902148.2019.1695019
Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease with unknown cause. While the drugs nintedanib and pirfenidone have been approved for the treatment of IPF, they only slow disease progression and can induce several side-effects, suggesting that there is still an unmet need to develop new efficacious drugs, and interventions strategies, to combat this disease. We have recently developed a sheep model of pulmonary fibrosis for the preclinical testing of novel anti-fibrotic drugs. The aim of this study was to assess the effects of pirfenidone to ascertain its suitability as a benchmark for comparing other novel therapeutics in this sheep model. To initiate localized fibrosis, sheep were given two infusions of bleomycin (0.6 U/ml per infusion), a fortnight apart, to a specific lung segment. The contralateral lung segment in each sheep was infused with saline to act as an internal control. Two weeks after the final bleomycin infusion, either pirfenidone or methylcellulose (vehicle control) were administered orally to sheep twice daily for 5 weeks. Results showed that sheep treated with pirfenidone had improved lung function, ameliorated fibrotic pathology, lower numbers of active myofibroblasts, and reduced extra cellular matrix deposition when compared with the relevant measurements obtained from control sheep treated with vehicle. This study showed that pirfenidone can attenuate bleomycin-induced pulmonary fibrosis in sheep, and can therefore be used as a positive control to assess other novel therapeutics for IPF in this model.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
Abstract: Relaxin attenuates tissue fibrosis in an organ- and age-specific manner. The antifibrotic actions of relaxin are mediated via an angiotensin type 2 receptor mechanism. Relaxin replacement therapy is a potential antifibrotic for cardiovascular and kidney disease in postmenopausal women. The antifibrotic effects of recombinant human relaxin (RLX) in the kidney are dependent on an interaction between its cognate receptor (RXFP1) and the angiotensin type 2 receptor (AT 2 R) in male models of disease. Whether RLX has therapeutic effects, which are also mediated via AT 2 R, in hypertensive adult and aged/reproductively senescent females is unknown. Thus, we determined whether treatment with RLX provides cardiorenal protection via an AT 2 R-dependent mechanism in adult and aged female stroke-prone spontaneously hypertensive rats (SHRSPs). In 6-month-old (6MO) and 15-month-old ([15MO] reproductively senescent) female SHRSP, systolic BP (SBP), GFR, and proteinuria were measured before and after 4 weeks of treatment with vehicle (Veh), RLX (0.5 mg/kg per day s.c.), or RLX+PD123319 (AT 2 R antagonist 3 mg/kg per day s.c.). Aortic endothelium–dependent relaxation and fibrosis of the kidney, heart, and aorta were assessed. In 6MO SHRSP, RLX significantly enhanced GFR by approximately 25% ( P =0.001) and reduced cardiac fibrosis ( P =0.01) as compared with vehicle-treated counterparts. These effects were abolished or blunted by PD123319 coadministration. In 15MO females, RLX reduced interstitial renal ( P =0.02) and aortic ( P =0.003) fibrosis and lowered SBP (13±3 mm Hg P =0.04) relative to controls. These effects were also blocked by PD123319 cotreatment (all P =0.05 versus RLX treatment alone). RLX also markedly improved vascular function by approximately 40% ( P .001) in 15MO SHRSP, but this was not modulated by PD123319 cotreatment. The antifibrotic and organ-protective effects of RLX, when administered to a severe model of hypertension, conferred cardiorenal protection in adult and reproductively senescent female rats to a great extent via an AT 2 R-mediated mechanism.
Publisher: MDPI AG
Date: 12-04-2022
DOI: 10.3390/BIOMEDICINES10040883
Abstract: Circulating bone marrow-derived endothelial progenitor cells (EPCs) facilitate vascular repair in several organs including the kidney but are progressively diminished in end-stage kidney disease (ESKD) patients, which correlates with cardiovascular outcomes and related mortality. We thus determined if enhancing the tissue-reparative effects of human bone marrow-derived mesenchymal stromal cells (BM-MSCs) with the vasculogenic effects of recombinant human relaxin (RLX) could promote EPC proliferation and function. CD34+ EPCs were isolated from the blood of healthy and ESKD patients, cultured until late EPCs had formed, then stimulated with BM-MSC-derived condition media (CM 25%), RLX (1 or 10 ng/mL), or both treatments combined. Whilst RLX alone stimulated EPC proliferation, capillary tube formation and wound healing in vitro, these measures were more rapidly and markedly enhanced by the combined effects of BM-MSC-derived CM and RLX in EPCs derived from both healthy and ESKD patients. These findings have important clinical implications, having identified a novel combination therapy that can restore and enhance EPC number and function in ESKD patients.
Publisher: JMIR Publications Inc.
Date: 19-12-2018
DOI: 10.2196/11228
Publisher: JMIR Publications Inc.
Date: 20-09-2018
Abstract: utrition and physical activity interventions are important components of cancer care. With an increasing demand for services, there is a need to consider flexible, easily accessible, and tailored models of care while maintaining optimal outcomes. his systematic review describes and appraises the efficacy of technology-supported self-guided nutrition and physical activity interventions for people with cancer. systematic search of multiple databases from 1973 to July 2018 was conducted for randomized and nonrandomized trials investigating technology-supported self-guided nutrition and physical activity interventions. Risk of bias was assessed using the Cochrane Risk of Bias tool. Outcomes included behavioural, health-related, clinical, health service, or financial measures. ixteen randomized controlled trials representing 2684 participants were included. Most studies were web-based interventions (n=9) and had a 12-week follow-up duration (n=8). Seven studies assessed dietary behaviour, of which two reported a significant benefit on diet quality or fruit and vegetable intake. Fifteen studies measured physical activity behaviour, of which eight studies reported a significant improvement in muscle strength and moderate-to-vigorous physical activity. Four of the nine studies assessing the health-related quality of life (HRQoL) reported a significant improvement in global HRQoL or a domain subscale. A significant improvement in fatigue was found in four of six studies. Interpretation of findings was influenced by inadequate reporting of intervention description and compliance. his review identified short-term benefits of technology-supported self-guided interventions on the physical activity level and fatigue and some benefit on dietary behaviour and HRQoL in people with cancer. However, current literature demonstrates a lack of evidence for long-term benefit. ROSPERO CRD42017080346 www.crd.york.ac.uk rospero/display_record.php?RecordID=80346
Publisher: Authorea, Inc.
Date: 16-12-2022
DOI: 10.22541/AU.167120673.35773330/V1
Abstract: Background and Purpose: This study investigated the reno-protective effects of a highly selective AT2R agonist peptide, β-Pro7Ang III in a mouse model of acute kidney injury (AKI). Experimental Approach: C57BL/6J mice underwent either sham surgery or unilateral kidney ischemia-reperfusion injury (IRI) for 40 minutes. IRI mice were treated with either β-Pro7Ang III or perindopril and at 7 days post-surgery the kidneys analysed for histopathology and the development of fibrosis and matrix metalloproteinase (MMP)-2 and -9 activity. The association of the therapeutic effects of β-Pro7Ang III with macrophage number and phenotype was determined in vivo and in vitro. Key Results: Decreased kidney tubular injury, interstitial matrix expansion and reduced interstitial immune cell infiltration in IRI mice receiving β-Pro7Ang III treatment was observed at day 7, compared to IRI mice without treatment. This correlated to reduced collagen accumulation and MMP-2 activity in IRI mice following β-Pro7Ang III treatment. FACS analysis showed a reduced number and proportion of CD45+CD11b+F4/80+ macrophages in IRI kidneys in response to β-Pro7Ang III, correlating with a significant increase in M2 macrophage markers and decreased M1 markers at day 3 and 7 post-IR injury, respectively. In vitro analysis of cultured THP-1 cells showed that β-Pro7Ang III attenuated lipopolysaccharide (LPS)-induced tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 production but increased IL-10 secretion, compared to LPS alone. Conclusion and Implications: Therapeutic delivery of β-Pro7Ang III was renoprotective via alteration of macrophage phenotype and anti-inflammatory cytokine release, therefore mitigating the downstream progression of ischemic AKI.
Publisher: Hindawi Limited
Date: 18-01-2023
DOI: 10.1155/2023/1522593
Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by excessive deposition of extracellular matrix in the interstitial lung parenchyma, often manifested by dyspnea and progressive loss of lung function. The role of inflammation in the pathogenesis of IPF is not well understood. This study evaluated the histopathological and inflammatory components of bleomycin-induced pulmonary fibrosis in mouse and sheep models, in terms of their ability to translate to the human IPF. Merino sheep (n = 8) were bronchoscopically administered with two bleomycin infusions, two weeks apart, into a caudal lung segment, with a saline (control) administered into a caudal segment in the opposite lung. Balb/c mice were twice intranasally instilled, one week apart, with either bleomycin (n = 7) or saline (control, n = 7). Lung s les were taken for the histopathological assessment 28 days in sheep and 21 days in mice after the first bleomycin administration. We observed tertiary lymphoid aggregates, in the fibrotic lung parenchyma of sheep, but not in mouse lung tissues exposed to bleomycin. B-cell and T-cell infiltration significantly increased in sheep lung tissues compared to mouse lung tissues due to bleomycin injury. Statistical analysis showed that the fibrotic score, fibrotic fraction, and tissue fraction significantly increased in sheep lung tissues compared to murine lung tissues. The presence of tertiary lymphoid aggregates in the lung parenchyma and increased infiltration of T-cells and B-cells, in the sheep model, may be useful for the future study of the underlying inflammatory disease mechanisms in the lung parenchyma of IPF patients.
Publisher: Springer Science and Business Media LLC
Date: 26-02-2020
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.CLNU.2022.03.024
Abstract: The Global Leadership Initiative on Malnutrition (GLIM) criteria require validation in various clinical populations. This study determined the prevalence of malnutrition in people with cancer using all possible diagnostic combinations of GLIM etiologic and phenotypic criteria and determined the combinations that best predicted mortality and unplanned hospital admission within 30 days. The GLIM criteria were applied, in a cohort of participants from two cancer malnutrition point prevalence studies (N = 2801), using 21 combinations of the phenotypic (≥5% unintentional weight loss, body mass index [BMI], subjective assessment of muscle stores [from PG-SGA]) and etiologic (reduced food intake, inflammation [using metastatic disease as a proxy]) criteria. Machine learning approaches were applied to predict 30-day mortality and unplanned admission. We analysed 2492 participants after excluding those with missing data. Overall, 19% (n = 485) of participants were malnourished. The most common GLIM combinations were weight loss and reduced food intake (15%, n = 376), and low muscle mass and reduced food intake (12%, n = 298). Machine learning models demonstrated malnutrition diagnosis by weight loss and reduced muscle mass plus either reduced food intake or inflammation were the most important combinations to predict mortality at 30-days (accuracy 88%). Malnutrition diagnosis by weight loss or reduced muscle mass plus reduced food intake was most important for predicting unplanned admission within 30-days (accuracy 77%). Machine learning demonstrated that the phenotypic criteria of weight loss and reduced muscle mass combined with either etiologic criteria were important for predicting mortality. In contrast, the etiologic criteria of reduced food intake in combination with weight loss or reduced muscle mass was important for predicting unplanned admission. Understanding the phenotypic and etiologic criteria contributing to the GLIM diagnosis is important in clinical practice to identify people with cancer at higher risk of adverse outcomes.
Publisher: Wiley
Date: 29-01-2013
Publisher: Wiley
Date: 10-02-2021
DOI: 10.1111/BPH.15361
Abstract: Fibrosis is a hallmark of chronic kidney disease (CKD) that significantly contributes to renal dysfunction, and impairs the efficacy of stem cell‐based therapies. This study determined whether combining bone marrow‐derived mesenchymal stem cells (BM‐MSCs) with the renoprotective effects of recombinant human relaxin (serelaxin) could therapeutically reduce renal fibrosis in mice with one kidney/deoxycorticosterone acetate/salt (1K/DOCA/salt)‐induced hypertension, compared with the effects of the ACE inhibitor, perindopril. Adult male C57BL/6 mice were uni‐nephrectomised and received deoxycorticosterone acetate and saline to drink (1K/DOCA/salt) for 21 days. Control mice were uni‐nephrectomised but received water over the same time period. Sub‐groups of 1K/DOCA/salt‐injured mice ( n = 5–8 per group) were treated with either serelaxin (0.5 mg·kg −1 ·day −1 ) or BM‐MSCs (1 × 10 6 per mouse) alone both treatments combined (with 0.5 × 10 6 or 1 × 10 6 BM‐MSCs per mouse) or perindopril (2 mg·kg −1 ·day −1 ) from days 14–21. 1K/DOCA/salt‐injured mice developed elevated BP and hypertension‐induced renal damage, inflammation and fibrosis. BM‐MSCs alone reduced the injury‐induced fibrosis and attenuated BP to a similar extent as perindopril. Serelaxin alone modestly reduced renal fibrosis and effectively reduced tubular injury. Strikingly, the combined effects of BM‐MSCs (at both doses) with serelaxin significantly inhibited renal fibrosis and proximal tubular epithelial injury while restoring renal architecture, to a greater extent than either therapy alone, and over the effects of perindopril. Combining BM‐MSCs and serelaxin provided broader renoprotection over either therapy alone or perindopril and might represent a novel treatment for hypertensive CKD.
Publisher: S. Karger AG
Date: 25-09-2020
DOI: 10.1159/000503634
Abstract: Neuroendocrine tumors (NETs) have increased in incidence and prevalence over the past 2 decades and affect approximately 170,000 people in the United States alone. Gastroenteropancreatic (GEP) NETs (GEP NET) are a heterogeneous group of rare tumors that have distinct effects on the body due to their tumor location and potential to secrete hormones and peptides. Clinical practice guidelines and consensus guidelines for GEP NETs with regard to best practice for diagnosis, treatment, and medical management are available, but the supportive care needs and optimal nutritional management of patients affected by these unique tumors remain under-researched: evidence to guide clinical practice is lacking. The pathophysiology of the disease and its treatment can cause various symptoms that can have significant effects on vitamin synthesis and absorption, dietary habits, weight change, and appetite. Deficiency of fat-soluble vitamins and niacin exists amongst patients with GEP NET, particularly those on treatment with somatostatin analogs and with serotonin-secreting tumors, respectively. Malnutrition and dietary modification amongst patients with GEP NET is more prevalent than initially thought: up to 25% of inpatients with GEP NET are malnourished. Food intolerance is also reported in up to 40–90% of these patients, though its misdiagnosis is common. This review summarizes the evidence regarding the impact of GEP NET and its treatment on nutritional factors in these patients with emphasis on malnutrition, vitamin deficiencies, dietary intake, and quality of life. Recommendations for clinical practice and research approaches to address these nutritional issues are discussed.
Publisher: Elsevier BV
Date: 02-2021
Publisher: MDPI AG
Date: 25-06-2022
DOI: 10.3390/IJMS23137074
Abstract: Chronic NLRP3 inflammasome activation can promote fibrosis through its production of interleukin (IL)-1β and IL-18. Conversely, recombinant human relaxin (RLX) can inhibit the pro-fibrotic interactions between IL-1β, IL-18 and transforming growth factor (TGF)-β1. Here, the broader extent by which RLX targeted the myofibroblast NLRP3 inflammasome to mediate its anti-fibrotic effects was elucidated. Primary human cardiac fibroblasts (HCFs), stimulated with TGF-β1 (to promote myofibroblast (HCMF) differentiation), LPS (to prime the NLRP3 inflammasome) and ATP (to activate the NLRP3 inflammasome) (T+L+A) or benzoylbenzoyl-ATP (to activate the ATP receptor P2X7R) (T+L+Bz), co-expressed relaxin family peptide receptor-1 (RXFP1), the angiotensin II type 2 receptor (AT2R) and P2X7R, and underwent increased protein expression of toll-like receptor (TLR)-4, NLRP3, caspase-1, IL-1β and IL-18. Whilst RLX co-administration to HCMFs significantly prevented the T+L+A- or T+L+Bz-stimulated increase in these end points, the inhibitory effects of RLX were annulled by the pharmacological antagonism of either RXFP1, AT2R, P2X7R, TLR-4, reactive oxygen species (ROS) or caspase-1. The RLX-induced amelioration of left ventricular inflammation, cardiomyocyte hypertrophy and fibrosis in isoproterenol (ISO)-injured mice, was also attenuated by P2X7R antagonism. Thus, the ability of RLX to ameliorate the myofibroblast NLRP3 inflammasome as part of its anti-fibrotic effects, appeared to involve RXFP1, AT2R, P2X7R and the inhibition of TLR-4, ROS and caspase-1.
Publisher: Hindawi Limited
Date: 11-11-2019
DOI: 10.1155/2019/1278301
Abstract: Aims . To date, the ROS-generating capacities of macrophages in different activation states have not been thoroughly compared. This study is aimed at determining the nature and levels of ROS generated following stimulation with common activators of M1 and M2 macrophages and investigating the potential for this to impact fibrosis. Results . Human primary and THP-1 macrophages were treated with IFN- γ +LPS or IL-4-activating stimuli, and mRNA expression of established M1 (CXCL11, CCR7, IL-1 β ) and M2 (MRC-1, CCL18, CCL22) markers was used to confirm activation. Superoxide generation was assessed by L-012-enhanced chemiluminescence and was increased in both M(IFN- γ +LPS) and M(IL-4) macrophages, as compared to unpolarised macrophages (M Φ ). This signal was attenuated with NOX2 siRNA. Increased expression of the p47phox and p67phox subunits of the NOX2 oxidase complex was evident in M(IFN- γ +LPS) and M(IL-4) macrophages, respectively. Amplex Red and DCF fluorescence assays detected increased hydrogen peroxide generation following stimulation with IL-4, but not IFN- γ +LPS. Coculture with human aortic adventitial fibroblasts revealed that M(IL-4), but not M(IFN- γ +LPS), enhanced fibroblast collagen 1 protein expression. Macrophage pretreatment with the hydrogen peroxide scavenger, PEG-catalase, attenuated this effect. Conclusion . We show that superoxide generation is not only enhanced with stimuli associated with M1 macrophage activation but also with the M2 stimulus IL-4. Macrophages activated with IL-4 also exhibited enhanced hydrogen peroxide generation which in turn increased aortic fibroblast collagen production. Thus, M2 macrophage-derived ROS is identified as a potentially important contributor to aortic fibrosis.
Publisher: Wiley
Date: 28-04-2021
Publisher: Wiley
Date: 31-03-2021
DOI: 10.1111/BPH.15428
Abstract: Oxidative stress and fibrosis are hallmarks of cardiomyopathy‐induced heart failure yet are not effectively targeted by current frontline therapies. Here, the therapeutic effects of the anti‐oxidant, N ‐acetylcysteine (NAC), were compared and combined with an acute heart failure drug with established anti‐fibrotic effects, serelaxin (RLX), in a murine model of cardiomyopathy. Adult male 129sv mice were subjected to repeated isoprenaline (25 mg·kg −1 )‐induced cardiac injury for five consecutive days and then left to undergo fibrotic healing until Day 14. Subgroups of isoprenaline‐injured mice were treated with RLX (0.5 mg·kg −1 ·day −1 ), NAC (25 mg·kg −1 ·day −1 ) or both combined, given subcutaneously via osmotic minipumps from Day 7 to 14. Control mice received saline instead of isoprenaline. Isoprenaline‐injured mice showed increased left ventricular (LV) inflammation (~5‐fold), oxidative stress (~1–2.5‐fold), cardiomyocyte hypertrophy (~25%), cardiac remodelling, fibrosis (~2–2.5‐fold) and dysfunction by Day 14 after injury. NAC alone blocked the cardiomyopathy‐induced increase in LV superoxide levels, to a greater extent than RLX. Additionally, either treatment alone only partly reduced several measures of LV inflammation, remodelling and fibrosis. In comparison, the combination of RLX and NAC prevented the cardiomyopathy‐induced LV macrophage infiltration, remodelling, fibrosis and cardiomyocyte size, to a greater extent than either treatment alone after 7 days. The combination therapy also restored the isoprenaline‐induced reduction in LV function, without affecting systolic BP. These findings demonstrated that the simultaneous targeting of oxidative stress and fibrosis is key to treating the pathophysiology and dysfunction induced by cardiomyopathy.
Publisher: MDPI AG
Date: 21-04-2022
Abstract: Fetal growth restriction (FGR) is commonly associated with placental insufficiency and inflammation. Nonetheless, the role played by inflammasomes in the pathogenesis of FGR is poorly understood. We hypothesised that placental inflammasomes are differentially expressed and contribute to the aberrant trophoblast function. Inflammasome gene expression profiles were characterised by real-time PCR on human placental tissues collected from third trimester FGR and gestation-matched control pregnancies (n = 25/group). The functional significance of a candidate inflammasome was then investigated using lipopolysaccharide (LPS)-induced models of inflammation in human trophoblast organoids, BeWo cells in vitro, and a murine model of FGR in vivo. Placental mRNA expression of NLRP3, caspases 1, 3, and 8, and interleukin 6 increased ( -fold), while that of the anti-inflammatory cytokine, IL-10, decreased ( -fold) in FGR compared with control pregnancies. LPS treatment increased NLRP3 and caspase-1 expression ( -fold) in trophoblast organoids and BeWo cell cultures in vitro, and in the spongiotrophoblast and labyrinth in the murine model of FGR. However, the LPS-induced rise in NLRP3 was attenuated by its siRNA-induced down-regulation in BeWo cell cultures, which correlated with reduced activity of the apoptotic markers, caspase-3 and 8, compared to the control siRNA-treated cells. Our findings support the role of the NLRP3 inflammasome in the inflammation-induced aberrant trophoblast function, which may contribute to FGR.
Publisher: MDPI AG
Date: 04-2023
DOI: 10.3390/IJMS24076616
Abstract: Human relaxin-2 (H2 relaxin) is therapeutically very important due to its strong anti-fibrotic, vasodilatory, and cardioprotective effects. Therefore, relaxin’s receptor, relaxin family peptide receptor 1 (RXFP1), is a potential target for the treatment of fibrosis and related disorders, including heart failure. H2 relaxin has a complex two-chain structure (A and B) and three disulfide bridges. Our laboratory has recently developed B7-33 peptide, a single-chain agonist based on the B-chain of H2 relaxin. However, the peptide B7-33 has a short circulation time in vitro in serum (t1/2 = ~6 min). In this study, we report structure-activity relationship studies on B7-33 utilizing different fatty-acid conjugations at different positions. We have shown that by fatty-acid conjugation with an appropriate spacer length, the in vitro half-life of B7-33 can be increased from 6 min to 60 min. In the future, the lead lipidated molecule will be studied in animal models to measure its PK/PD properties, which will lead to their pre-clinical applications.
Publisher: JMIR Publications Inc.
Date: 05-06-2018
Abstract: astroenteropancreatic neuroendocrine tumors (GEP NETs) are a heterogeneous group of tumors with distinct effects on the body due to their potential to secrete hormones and peptides. The incidence and prevalence of GEP NETs in Australia are rising. During 2000-2006, the annual incidence was approximately 3.3 per 100,000 population. To date, there has been development of clinical practice and consensus guidelines for NETs covering best practice for diagnosis, treatment, and medical management however, the supportive care needs and optimal nutritional management of patients affected by NETs remains underresearched, and evidence to guide clinical practice is lacking. While there is emerging research describing the extent of morbidity in different types of GEP NET patients, little is known about the experience of people affected by these tumors and how nutritional status is impacted by either diagnosis or treatment. he objective of this study was to explore nutrition-related complications and quality of life of patients diagnosed with a GEP NET and to generate evidence to inform future research and development of nutrition screening and management practices. atients diagnosed with a GEP NET at two metropolitan recruitment sites will be invited to participate in a 6-month, mixed-methods longitudinal study. Participants recruited to the study will receive usual care and participate in data collection for the study at 4 time points (at recruitment and 2, 4, and 6 months postrecruitment). Study data will include nutritional status, body weight, fat-free mass, and patient-reported outcome measures (dietitian contact, disease-related symptom presence and severity, dietary habits, health-related quality of life, psychological morbidity, and financial impact). At recruitment and 6 months postrecruitment, complete nutrient testing, including relevant plasma vitamin levels, will also be undertaken. A purposive s le of participants will be invited to take part in semistructured interviews to explore the experience of living with a GEP NET and associated nutrition complications. thics approval has been obtained, and study recruitment and data collection are underway. his study will provide the first in-depth, comprehensive description of nutritional issues in patients with GEP NETs. Results will advance the knowledge of nutritional issues faced by patients with GEP NETs and help inform the development of screening tools and clinical practice guidelines. ERR1-10.2196/11228
Publisher: MDPI AG
Date: 13-11-2020
DOI: 10.3390/NU12113493
Abstract: Malnutrition is highly prevalent in people with head and neck cancer (HCN) and is associated with poorer outcomes. However, variation in malnutrition diagnostic criteria has made translation of the most effective interventions into practice challenging. This study aimed to determine the prevalence of malnutrition in a HNC population according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and assess inter-rater reliability and predictive validity. A secondary analysis of data available for 188 patients with HNC extracted from two cancer malnutrition point prevalence studies was conducted. A GLIM diagnosis of malnutrition was assigned when one phenotypic and one etiologic criterion were present. Phenotypic criteria were ≥5% unintentional loss of body weight, body mass index (BMI), and subjective evidence of muscle loss. Etiologic criteria were reduced food intake, and presence of metastatic disease as a proxy for inflammation. The prevalence of malnutrition was 22.6% (8.0% moderately malnourished 13.3% severely malnourished). Inter-rater reliability was classified as excellent for the GLIM criteria overall, as well as for each in idual criterion. A GLIM diagnosis of malnutrition was found to be significantly associated with BMI but was not predictive of 30 day hospital readmission. Further large, prospective cohort studies are required in this patient population to further validate the GLIM criteria.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2020
Publisher: Wiley
Date: 17-08-2020
Abstract: This position statement describes the recommendations of the Clinical Oncology Society of Australia (COSA) regarding management of cancer‐related malnutrition and sarcopenia. A multidisciplinary working group completed a review of the literature, focused on evidence‐based guidelines, systematic reviews and meta‐analyses, to develop recommendations for the position statement. National consultation of the position statement content was undertaken through COSA members. All people with cancer should be screened for malnutrition and sarcopenia in all health settings at diagnosis and as the clinical situation changes throughout treatment and recovery. People identified as “at risk” of malnutrition or with a high‐risk cancer diagnosis or treatment plan should have a comprehensive nutrition assessment people identified as “at risk” of sarcopenia should have a comprehensive evaluation of muscle status using a combination of assessments for muscle mass, muscle strength and function. All people with cancer‐related malnutrition and sarcopenia should have access to the core components of treatment, including medical nutrition therapy, targeted exercise prescription and physical and psychological symptom management. Treatment for cancer‐related malnutrition and sarcopenia should be in idualised, in collaboration with the multidisciplinary team (MDT), and tailored to meet needs at each stage of cancer treatment. Health services should ensure a broad range of health care professionals across the MDT have the skills and confidence to recognise malnutrition and sarcopenia to facilitate timely referrals and treatment. The position statement is expected to provide guidance at a national level to improve the multidisciplinary management of cancer‐related malnutrition and sarcopenia.
Publisher: Wiley
Date: 21-01-2013
DOI: 10.1111/JHN.12036
Abstract: The present study describes the development of evidence-based practice guidelines for the nutritional management of adult patients with head and neck cancer using a wiki platform to enable wide international stakeholder consultation and maintain currency. A dietitian steering committee and a multidisciplinary steering committee were established for consultation. Traditional methods of evidence-based guideline development were utilised to perform the literature review, assess the evidence and produce a draft document. This was transferred to a wiki platform for stakeholder consultation and international endorsement processes in Australia, New Zealand and the UK. Data were collected on website traffic utilising Google Analytics. In addition to broad stakeholder consultation through the steering committees, an additional twenty comments were received via the wiki by twelve in iduals covering six different professions from three different countries, compared to four comments by e-mail. The guidelines were subsequently endorsed by the dietetic associations of Australia, New Zealand and the UK. During a 4-month period monitoring the use of the guidelines, there were 2303 page views to the landing page from 33 countries. The average number of pages accessed per visit was five and the duration of time spent on the website was approximately 6 min. Using a wiki platform for guideline development and dissemination is a successful method for producing high-quality resources that can undergo wide international stakeholder review and include open public consultation. This can replace conventional methods whereby guidelines can quickly become outdated.
Publisher: MDPI AG
Date: 04-02-2021
DOI: 10.3390/NU13020514
Abstract: Background: Patients undergoing (chemo) radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) are at high risk of malnutrition during and after treatment. Malnutrition can lead to poor tolerance to treatment, treatment interruptions, poor quality of life (QOL) and potentially reduced survival rate. Human papillomavirus (HPV) is now known as the major cause of OPSCC. However, research regarding its effect on nutritional outcomes is limited. The aim of this study was to examine the relationship between HPV status and nutritional outcomes, including malnutrition and weight loss during and after patients’ (chemo) radiotherapy treatment for OPSCC. Methods: This was a longitudinal cohort study comparing the nutritional outcomes of HPV-positive and negative OPSCC patients undergoing (chemo) radiotherapy. The primary outcome was nutritional status as measured using the Patient Generated-Subjective Global Assessment (PG-SGA). Secondary outcomes included loss of weight, depression, QOL and adverse events. Results: Although HPV-positive were less likely to be malnourished according to PG-SGA at the beginning of treatment, we found that the difference between malnutrition rates in response to treatment was not significantly different over the course of radiotherapy and 3 months post treatment. HPV-positive participants had significantly higher odds of experiencing % weight loss at three months post-treatment than HPV-negative participants (OR = 49.68, 95% CI (2.7, 912.86) p ≤ 0.01). Conclusions: The nutritional status of HPV positive and negative patients were both negatively affected by treatment and require similarly intense nutritional intervention. In acute recovery, HPV positive patients may require more intense intervention. At 3- months post treatment, both groups still showed nutritional symptoms that require nutritional intervention so ongoing nutritional support is essential.
Publisher: Wiley
Date: 12-07-2022
DOI: 10.1111/JHN.12930
Abstract: Nutrition post major upper gastrointestinal (UGI) cancer surgery is a significant consideration known to affect postoperative recovery and the ability to tolerate adjuvant treatment. This systematic review assessed the effect of early oral feeding (EOF), compared to traditional timing of oral feeding, following major surgery for UGI cancer on postoperative complications, postoperative length of hospital stay (LOS), nutritional status and quality of life (QOL). The literature was searched up to March 9th 2020 using CINHAL, PubMed, MEDLINE, Embase, Scopus and Web of Science databases. Quality assessment was completed using the Academy of Nutrition and Dietetics quality criteria checklist. Fifteen articles were included, consisting of seven randomised controlled trials, six cohort studies and two non‐randomised trials, with a total of 2517 participants. The type and timing of EOF varied considerably across studies with limited reporting of energy and protein intakes from oral or enteral feeding. Fourteen studies assessed postoperative complications of which 13 reported no difference between EOF and standard care. Fourteen studies assessed postoperative LOS and of these, 13 reported a reduced length of stay in the EOF group. Four of 15 studies assessing nutritional status found no difference between groups. Three of 15 studies assessed QOL with inconsistent findings. This review found EOF reduced postoperative LOS and did not increase postoperative complications. However, the optimal timing for the introduction of EOF could not be established. Furthermore, the type of EOF varied considerably making comparison across studies challenging and demonstrates a need for internationally standardised definitions.
Publisher: BMJ
Date: 09-2021
DOI: 10.1136/BMJOPEN-2021-051665
Abstract: Low muscle mass and low muscle attenuation (radiodensity), reflecting increased muscle adiposity, are prevalent muscle abnormalities in people with lung cancer receiving curative intent chemoradiation therapy (CRT) or radiation therapy (RT). Currently, there is a limited understanding of the magnitude, determinants and clinical significance of these muscle abnormalities in the lung cancer CRT/RT population. The primary objective of this study is to identify the predictors of muscle abnormalities (low muscle mass and muscle attenuation) and their depletion over time in people with lung cancer receiving CRT/RT. Secondary objectives are to assess the magnitude of change in these parameters and their association with health-related quality of life, treatment completion, toxicities and survival. Patients diagnosed with lung cancer and planned for treatment with CRT/RT are invited to participate in this prospective observational study, with a target of 120 participants. The impact and predictors of muscle abnormalities (assessed via CT at the third lumbar vertebra) prior to and 2 months post CRT/RT on the severity of treatment toxicities, treatment completion and survival will be assessed by examining the following variables: demographic and clinical factors, weight loss, malnutrition, muscle strength, physical performance, energy and protein intake, physical activity and sedentary time, risk of sarcopenia (Strength, Assistance in walking, Rise from a chair, Climb stairs, Falls history (SARC-F) score alone and with calf-circumference) and systemic inflammation. A s le of purposively selected participants with muscle abnormalities will be invited to take part in semistructured interviews to understand their ability to cope with treatment and explore preference for treatment strategies focused on nutrition and exercise. The PREDICT study received ethics approval from the Human Research Ethics Committee at Peter MacCallum Cancer Centre (HREC/53147/PMCC-2019) and Deakin University (2019-320). Findings will be disseminated through peer review publications and conference presentations.
Publisher: Research Square Platform LLC
Date: 23-08-2021
DOI: 10.21203/RS.3.RS-787983/V1
Abstract: Sulforaphane has been investigated in human pathologies and preclinical models of airway diseases. To provide further mechanistic insights, we explored L-sulforaphane (LSF) in the ovalbumin (OVA)-induced chronic allergic airways murine model, with key hallmarks of asthma. Histological analysis indicated that LSF prevented or reversed OVA-induced epithelial thickening, collagen deposition, goblet cell metaplasia, and inflammation. Well-known antioxidant and anti-inflammatory mechanisms contribute to the beneficial effects of LSF. Fourier transform infrared microspectroscopy revealed altered composition of macromolecules, including lipids, following OVA-sensitization, which were restored by LSF. RNA sequencing in human peripheral blood mononuclear cells highlighted the anti-inflammatory signature of LSF. Novel findings indicated that LSF reduced the expression and activity of histone deacetylase 8. Further, LSF resulted in histone and α-tubulin hyperacetylation in vivo. More generally, this study identified new epigenetic regulatory mechanisms accounting for the protective effects and provide support for the potential clinical utility of LSF in allergic airways disease.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2021
Publisher: MDPI AG
Date: 14-11-2022
Abstract: A high salt (HS) diet is associated with an increased risk for cardiovascular diseases (CVDs) and fibrosis is a key contributor to the organ dysfunction involved in CVDs. The activation of the renin angiotensin type 2 receptor (AT2R) has been considered as organ protective in many CVDs. However, there are limited AT2R-selective agonists available. Our first reported β-substituted angiotensin III peptide, β-Pro7-AngIII, showed high selectivity for the AT2R. In the current study, we examine the potential anti-fibrotic and anti-inflammatory effects of this novel AT2R-selective peptide on HS-induced organ damage. FVB/N mice fed with a 5% HS diet for 8 weeks developed cardiac and renal fibrosis and inflammation, which were associated with increased TGF-β1 levels in heart, kidney and plasma. Four weeks’ treatment (from weeks 5–8) with β-Pro7-AngIII inhibited the HS-induced cardiac and renal fibrosis and inflammation. These protective effects were accompanied by reduced local and systemic TGF-β1 as well as reduced cardiac myofibroblast differentiation. Importantly, the anti-fibrotic and anti-inflammatory effects caused by β-Pro7-AngIII were attenuated by the AT2R antagonist PD123319. These results demonstrate, for the first time, the cardio- and reno-protective roles of the AT2R-selective β-Pro7-AngIII, highlighting it as an important therapeutic that can target the AT2R to treat end-organ damage.
Publisher: JMIR Publications Inc.
Date: 12-02-2019
DOI: 10.2196/12281
Publisher: Wiley
Date: 26-07-2021
DOI: 10.1002/PBC.29243
Abstract: Current knowledge of the long‐term health behaviours and well‐being of adolescent and yong adult (AYA) cancer survivors is limited. The aim of this study was to evaluate the health behaviours of AYA cancer survivors compared to Australian normative data and describe their health‐related quality of life (HR‐QoL) and levels of fatigue. A cross‐sectional online survey of participants aged 15–25 years at diagnosis and 2–7 years post treatment completion was conducted at a comprehensive cancer centre. Validated questionnaires assessed health behaviours and functioning including current physical activity (PA) levels, diet quality, fatigue (FACIT‐F) and HR‐QoL (AQoL‐6D, Short Form 36v2 [SF‐36v2]) were compared to Australian normative data. Ninety in iduals completed the survey (26% response rate) with a mean age of 25.4 years and median time post treatment of 61 months (24–85 months). Compared to normative data, a higher proportion of AYA cancer survivors was consuming the recommended daily serves of fruit and vegetables (16.7% vs. 3.9%, p .0001), had a lower presence of overweight or obesity (46.7% vs. 57.7%, p = .04) and lower percentage of current smokers (2.2% vs. 16.7%, p .0001). However, AYA cancer survivors reported increased fatigue ( t [d f = 596] = −4.1, p .0001) and reduced HR‐QoL compared to normative data ( t [d f = 533] = 9.2, p .0001) along with a higher proportion suffering from one or more chronic health conditions (65% vs. 40%, p .0001). AYA cancer survivors from a single Australian institution, who were on average 5 years post treatment, exhibited better health behaviours compared to Australian normative data, but still below recommended guidelines. However, they continue to experience issues with fatigue and reduced HR‐QoL, especially in those not meeting the PA guidelines.
No related grants have been discovered for Chrishan Samuel.