Project description:Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Comprehensively capturing the host physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index and APACHE II score were poor predictors of survival. Instead, using plasma proteomes quantifying 302 plasma protein groups at 387 timepoints in 57 critically ill patients on invasive mechanical ventilation, we found 14 proteins that showed trajectories different between survivors and non-survivors. A proteomic predictor trained on single samples obtained at the first time point at maximum treatment level (i.e. WHO grade 7) and weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81, n=49). We tested the established predictor on an independent validation cohort (AUROC of 1.0, n=24). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that predictors derived from plasma protein levels have the potential to substantially outperform current prognostic markers in intensive care.

2022-03-03 | PXD029009 | Pride

Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases can be used to guide therapy

Project description:Purpose: Colorectal cancer (CRC) patients with peritoneal metastases (CRPM) have limited treatment options and the lowest CRC survival rates. We aimed to determine whether organoid testing could help guide precision treatment for CRPM patients, as the clinical utility of prospective, functional drug screening including non-standard agents is unknown. Experimental Design: CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing. Results: Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for 2 patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications. Conclusions: Our approach is feasible, reproducible and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.

2020-05-31 | GSE147971 | GEO

RockDove Parental Care

Project description:RockDove Parental Care

| PRJEB28684 | ENA

EJP CARE - SVA

Project description:EJP CARE - SVA

| PRJEB48129 | ENA

CARE

Project description:whole genome sequencing data from the CARE consortium @FZB

| PRJEB41518 | ENA

Gene expression profile at single cell level of bulk liver allograft tissue isolated 12 months post-transplant in patients receiving regulatory dendritic cell therapy (STUDY) and reference standard-of-care patients (SOC)

Project description:Regulatory dendritic cell therapy has shown potential in modulating the effector immune response after liver transplant in precliical models . We used single cell RNA sequencing (scRNA-seq) to analyze the differences in immune cell landscape of liver allograft at 12 months post-transplant in patients infused with regulatory dendritic cell therapy compared to standard-of-care control patients.

2023-06-01 | GSE218121 | GEO

Early predictive factors of mortality in onco-hematology patients admitted to the Intensive Care Unit for septic shock: A proteomic approach.

Project description:The number of organ failures at intensive care unit (ICU) admission is the main prognostic factor in septic shock. The aim was to assess classical clinico-biological parameters evaluating organ dysfunctions at ICU admission, combined with proteomics analysis, on day-30 mortality in critically ill onco-hematology patients admitted to the ICU for septic shock.

2018-08-22 | PXD004001 | Pride

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