DSpace Community:https://hdl.handle.net/2440/2962024-03-29T11:49:48Z2024-03-29T11:49:48ZUrine congophilia associated with preeclampsia does not persist 6-months postpartumHofstee, P.Lum, J.S.Chow, Y.Y.Wittwer, M.R.Arstall, M.Dekker, G.Clifton, V.L.Wright, I.M.Kelly, M.A.Ecroyd, H.https://hdl.handle.net/2440/1404292024-02-27T02:49:30Z2024-01-01T00:00:00ZTitle: Urine congophilia associated with preeclampsia does not persist 6-months postpartum
Author: Hofstee, P.; Lum, J.S.; Chow, Y.Y.; Wittwer, M.R.; Arstall, M.; Dekker, G.; Clifton, V.L.; Wright, I.M.; Kelly, M.A.; Ecroyd, H.
Abstract: Introduction: Preeclampsia is a common hypertensive disorder of pregnancy. Several studies have demonstrated that protein aggregates, detected through urine congophilia, is associated with preeclampsia; however, it has yet to be investigated whether urine congophilia remains postpartum in these women. In this study, we aimed to augment prior studies and determine whether urine congophilia is present postpartum. Methods: Women were recruited from Lyell McEwin Hospital, South Australia. Urine samples were collected during pregnancy and 6-months postpartum from women with non-preeclampsia pregnancies (n = 48) and women with pregnancies complicated by preeclampsia (n = 42). A Congo Red Dot blot test, total protein and creatinine levels from urine, as well as serum Soluble fms-like tyrosine kinase 1 to placental growth factor ratio (sFlt-1:PlGF), were assessed and correlated. Results: Preeclamptic women exhibited increased urine congophilia (P < 0.01), sFlt-1:PlGF ratio (P < 0.0001) and total protein (P < 0.01) during pregnancy; with a positive correlation between urine congophilia and total protein across the entire cohort (P < 0.0001). Although urine congophilia was no longer detected 6-months postpartum in preeclamptic women, total protein remained elevated (P < 0.05). sFlt-1:PlGF ratio during pregnancy was positively correlated with congophilia across the cohort (P = 0.0007). Serum creatinine was also higher in preeclamptic women during pregnancy (P < 0.001). Discussion: These results support that urine congophilia is significantly elevated in pregnancies complicated with preeclampsia and show that it does not continue postpartum, although larger cohort studies are needed to determine its feasibility as a diagnostic marker.2024-01-01T00:00:00ZIdentification of consensus head and neck cancer-associated microbiota signatures: a systematic review and meta-analysis of 16S rRNA and The Cancer Microbiome Atlas datasetsYeo, K.Li, R.Wu, F.Bouras, G.Mai, L.T.H.Smith, E.Wormald, P.-J.Valentine, R.Psaltis, A.J.Vreugde, S.Fenix, K.https://hdl.handle.net/2440/1404232024-02-18T23:49:53Z2024-01-01T00:00:00ZTitle: Identification of consensus head and neck cancer-associated microbiota signatures: a systematic review and meta-analysis of 16S rRNA and The Cancer Microbiome Atlas datasets
Author: Yeo, K.; Li, R.; Wu, F.; Bouras, G.; Mai, L.T.H.; Smith, E.; Wormald, P.-J.; Valentine, R.; Psaltis, A.J.; Vreugde, S.; Fenix, K.
Abstract: Introduction. Multiple reports have attempted to describe the tumour microbiota in head and neck cancer (HNSC).Gap statement. However, these have failed to produce a consistent microbiota signature, which may undermine understanding the importance of bacterial-mediated effects in HNSC.Aim. The aim of this study is to consolidate these datasets and identify a consensus microbiota signature in HNSC.Methodology. We analysed 12 published HNSC 16S rRNA microbial datasets collected from cancer, cancer-adjacent and non-cancer tissues to generate a consensus microbiota signature. These signatures were then validated using The Cancer Microbiome Atlas (TCMA) database and correlated with the tumour microenvironment phenotypes and patient's clinical outcome.Results. We identified a consensus microbial signature at the genus level to differentiate between HNSC sample types, with cancer and cancer-adjacent tissues sharing more similarity than non-cancer tissues. Univariate analysis on 16S rRNA datasets identified significant differences in the abundance of 34 bacterial genera among the tissue types. Paired cancer and cancer-adjacent tissue analyses in 16S rRNA and TCMA datasets identified increased abundance in Fusobacterium in cancer tissues and decreased abundance of Atopobium, Rothia and Actinomyces in cancer-adjacent tissues. Furthermore, these bacteria were associated with different tumour microenvironment phenotypes. Notably, high Fusobacterium signature was associated with high neutrophil (r=0.37, P<0.0001), angiogenesis (r=0.38, P<0.0001) and granulocyte signatures (r=0.38, P<0.0001) and better overall patient survival [continuous: HR 0.8482, 95 % confidence interval (CI) 0.7758-0.9273, P=0.0003].Conclusion. Our meta-analysis demonstrates a consensus microbiota signature for HNSC, highlighting its potential importance in this disease.
Description: Published 01 February 20242024-01-01T00:00:00ZInternational Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian PatientsTeras, J.Kroon, H.M.Miura, J.T.Kenyon-Smith, T.Beasley, G.M.Mullen, D.Farrow, N.E.Mosca, P.J.Lowe, M.C.Farley, C.R.Potdar, A.Daou, H.Sun, J.Carr, M.Farma, J.M.Henderson, M.A.Speakman, D.Serpell, J.Delman, K.A.Smithers, B.M.et al.https://hdl.handle.net/2440/1404182024-02-22T06:07:58Z2020-01-01T00:00:00ZTitle: International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients
Author: Teras, J.; Kroon, H.M.; Miura, J.T.; Kenyon-Smith, T.; Beasley, G.M.; Mullen, D.; Farrow, N.E.; Mosca, P.J.; Lowe, M.C.; Farley, C.R.; Potdar, A.; Daou, H.; Sun, J.; Carr, M.; Farma, J.M.; Henderson, M.A.; Speakman, D.; Serpell, J.; Delman, K.A.; Smithers, B.M.; et al.
Abstract: BACKGROUND:Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). PATIENTS AND METHODS:ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used. RESULTS:Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80-100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29-79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively. CONCLUSIONS:ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.2020-01-01T00:00:00ZMultiomic analysis implicates nuclear hormone receptor signalling in clustering epilepsyde Nys, R.van Eyk, C.L.Ritchie, T.Møller, R.S.Scheffer, I.E.Marini, C.Bhattacharjee, R.Kumar, R.Gecz, J.https://hdl.handle.net/2440/1404142024-02-27T02:40:12Z2024-01-01T00:00:00ZTitle: Multiomic analysis implicates nuclear hormone receptor signalling in clustering epilepsy
Author: de Nys, R.; van Eyk, C.L.; Ritchie, T.; Møller, R.S.; Scheffer, I.E.; Marini, C.; Bhattacharjee, R.; Kumar, R.; Gecz, J.
Abstract: Clustering Epilepsy (CE) is an epileptic disorder with neurological comorbidities caused by heterozygous variants of the X chromosome gene Protocadherin 19 (PCDH19). Recent studies have implicated dysregulation of the Nuclear Hormone Receptor (NHR) pathway in CE pathogenesis. To obtain a comprehensive overview of the impact and mechanisms of loss of PCDH19 function in CE pathogenesis, we have performed epigenomic, transcriptomic and proteomic analysis of CE relevant models. Our studies identified differential regulation and expression of Androgen Receptor (AR) and its targets in CE patient skin fibroblasts. Furthermore, our cell culture assays revealed the repression of PCDH19 expression mediated through ERα and the co-regulator FOXA1. We also identified a protein-protein interaction between PCDH19 and AR, expanding upon the intrinsic link between PCDH19 and the NHR pathway. Together, these results point to a novel mechanism of NHR signaling in the pathogenesis of CE that can be explored for potential therapeutic options.2024-01-01T00:00:00Z