Project description:Multiple organ dysfunction syndrome (MODS) can result from a variety of initiating events such as infection or trauma. The clinical condition of some MODS patients may deteriorate and require intense resource and high-risk cardiopulmonary support via extracorporeal membrane oxygenation (ECMO). Until now, no diagnostic criteria/molecular biomarker has been developed to identify MODS patients who require subsequent ECMO support. We used multi-time point (0h, 72h and 8d) whole transcriptomics from total blood of 27 patients (contro-4, MODS-17 and ECMO-6) to derived the molecular signatures to diagnose the MODS patients required ECMO support. We observed that immune response (neutrophil level) was compromised in MODS patients, who required ECMO support. Differential gene expression analysis and gene ontology enrichment has revealed that epigenetic modifications has got activated during the MODS deterioration to ECMO. In addition, signature of 6 genes were identified using logistic regression, which can be used as putative diagnostic markers for patients needed ECMO support.
Project description:Prognosis for cardiogenic shock patients under ECMO was our study goal. Success defined as survived more than 7 days after ECMO installation and failure died or had multiple organ failure in 7 days. Total 34 cases were enrolled, 17 success and 17 failure. Peripheral blood mononuclear cells collected at ECMO installation were used analyzed.
Project description:Prognosis for cardiogenic shock patients under ECMO was our study goal. Success defined as survived more than 7 days after ECMO installation and failure died or had multiple organ failure in 7 days. Total 34 cases were enrolled, 17 success and 17 failure. Peripheral blood mononuclear cells collected at ECMO installation 0, 2 hours and removal were analyzed.
Project description:Prognosis for cardiogenic shock patients under ECMO was our study goal. Success defined as survived more than 7 days after ECMO installation and failure died or had multiple organ failure in 7 days. Total 34 cases were enrolled, 17 success and 17 failure. Peripheral blood mononuclear cells collected at ECMO installation 0hr, 2hr and removal were used analyzed.
Project description:Extracorporeal membrane oxygenation (ECMO) has been increasingly applied to both adult and paediatric patients worldwide. However, continuous contact between blood and foreign surface of the ECMO circuit may contribute to haemostatic, inflammatory and other physiological disturbances during ECMO. Although previous studies have extensively investigated blood samples from patients on ECMO, the protein and cellular binding to the ECMO circuit has largely been overlooked as an additional factor that could contribute to differences in clinical outcomes. The detailed protocol described in this paper enables the comprehensive characterisation of protein and cellular binding in paediatric ECMO circuits, which could extend our knowledge of the pathophysiology of circuit binding and provide guidance for improved ECMO circuit design.
Project description:We profiled RNA expression by means of single cell RNA-Seq from a total of ~60,000 cells from 38 patients undergoing VA-ECMO due to acute heart failure (including acute exacerbation of chronic failure). Samples were taken at the time of initiation of ECMO (mean +/- 79 minutes from cannulation).
Project description:The present study aims to characterise proteins bound to circuits collected from children on extracorporeal membrane oxygenation (ECMO). ECMO circuits were collected from 6 patients. Quantification of concentrations for proteins bound to the ECMO circuit samples was performed using bicinchoninic acid (BCA) protein assay, whilst characterisation of the bound proteome was performed using Data-independent acquisition Mass Spectrometry (DIA-MS). Reactome Over-representation Pathway Analyses tool was used to identify functional pathways corresponding to the common proteins bound to circuits across all patients.
Project description:Chronic pain is a debilitating and poorly-treated condition. The mechanisms underlying the development of chronic pain are not well understood. Nerve injury and inflammation cause alterations in gene expression in tissues associated with transmission of pain, supporting molecular and cellular mechanisms that maintain painful states. Previous studies in animal models and human patients suffering from different chronic pain conditions have examined changes in transcriptome associated with chronic pain. However, in most studies, the analyses were restricted to a single tissue or pain condition. In the current study, we performed next-generation sequencing of dorsal root ganglia, spinal cord, brain and blood in mouse models of nerve injury and inflammation-induced chronic pain. Comparative analyses of differentially expressed genes (DEG) across these tissues in two pain models identified the extracellular matrix organization (ECMO) pathway as the most commonly affected pathway. Interestingly, examination of GWAS datasets revealed an over-representation of DEGs within the ECMO pathway in SNPs most strongly associated with human back pain. Remarkably, manipulation of the extracellular matrix in the mouse significantly affected the development of pain hypersensitivity following nerve injury, supporting our gene expression findings. In summary, our comprehensive analysis of transcriptional landscape across different mouse pain models and tissues as well as human GWAS datasets identified extracellular matrix organization as a central molecular pathway in the development of chronic pain.
