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Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients.

ABSTRACT: In trauma patients, shock-induced endotheliopathy (SHINE) is associated with a poor prognosis. We have previously identified four metabolic phenotypes in a small cohort of trauma patients (N = 20) and displayed the intracellular metabolic profile of the endothelial cell by integrating quantified plasma metabolomic profiles into a genome-scale metabolic model (iEC-GEM). A retrospective observational study of 99 trauma patients admitted to a Level 1 Trauma Center. Mass spectrometry was conducted on admission samples of plasma metabolites. Quantified metabolites were analyzed by computational network analysis of the iEC-GEM. Four plasma metabolic phenotypes (A-D) were identified, of which phenotype D was associated with an increased injury severity score (p < 0.001); 90% (91.6%) of the patients who died within 72 h possessed this phenotype. The inferred EC metabolic patterns were found to be different between phenotype A and D. Phenotype D was unable to maintain adequate redox homeostasis. We confirm that trauma patients presented four metabolic phenotypes at admission. Phenotype D was associated with increased mortality. Different EC metabolic patterns were identified between phenotypes A and D, and the inability to maintain adequate redox balance may be linked to the high mortality.

SUBMITTER: Henriksen HH

PROVIDER: S-EPMC9916682 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients.

Henriksen Hanne H HH Marín de Mas Igor I Nielsen Lars K LK Krocker Joseph J Stensballe Jakob J Karvelsson Sigurður T ST Secher Niels H NH Rolfsson Óttar Ó Wade Charles E CE Johansson Pär I PI

International journal of molecular sciences 20230123 3

In trauma patients, shock-induced endotheliopathy (SHINE) is associated with a poor prognosis. We have previously identified four metabolic phenotypes in a small cohort of trauma patients (N = 20) and displayed the intracellular metabolic profile of the endothelial cell by integrating quantified plasma metabolomic profiles into a genome-scale metabolic model (iEC-GEM). A retrospective observational study of 99 trauma patients admitted to a Level 1 Trauma Center. Mass spectrometry was conducted o ...[more]

PMID: 36768579

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Project description:PurposeThis study investigated the prognostic potential of intra-treatment PET radiomics data in patients undergoing definitive (chemo) radiation therapy for oropharyngeal cancer (OPC) on a prospective clinical trial. We hypothesized that the radiomic expression of OPC tumors after 20 Gy is associated with recurrence-free survival (RFS).Materials and methodsSixty-four patients undergoing definitive (chemo)radiation for OPC were prospectively enrolled on an IRB-approved study. Investigational 18 F-FDG-PET/CT images were acquired prior to treatment and 2 weeks (20 Gy) into a seven-week course of therapy. Fifty-five quantitative radiomic features were extracted from the primary tumor as potential biomarkers of early metabolic response. An unsupervised data clustering algorithm was used to partition patients into clusters based only on their radiomic expression. Clustering results were naïvely compared to residual disease and/or subsequent recurrence and used to derive Kaplan-Meier estimators of RFS. To test whether radiomic expression provides prognostic value beyond conventional clinical features associated with head and neck cancer, multivariable Cox proportional hazards modeling was used to adjust radiomic clusters for T and N stage, HPV status, and change in tumor volume.ResultsWhile pre-treatment radiomics were not prognostic, intra-treatment radiomic expression was intrinsically associated with both residual/recurrent disease (P = 0.0256, χ2 test) and RFS (HR = 7.53, 95% CI = 2.54-22.3; P = 0.0201). On univariate Cox analysis, radiomic cluster was associated with RFS (unadjusted HR = 2.70; 95% CI = 1.26-5.76; P = 0.0104) and maintained significance after adjustment for T, N staging, HPV status, and change in tumor volume after 20 Gy (adjusted HR = 2.69; 95% CI = 1.03-7.04; P = 0.0442). The particular radiomic characteristics associated with outcomes suggest that metabolic spatial heterogeneity after 20 Gy portends complete and durable therapeutic response. This finding is independent of baseline metabolic imaging characteristics and clinical features of head and neck cancer, thus providing prognostic advantages over existing approaches.ConclusionsOur data illustrate the prognostic value of intra-treatment metabolic image interrogation, which may potentially guide adaptive therapy strategies for OPC patients and serve as a blueprint for other disease sites. The quality of our study was strengthened by its prospective image acquisition protocol, homogenous patient cohort, relatively long patient follow-up times, and unsupervised clustering formalism that is less prone to hyper-parameter tuning and over-fitting compared to supervised learning.

Project description:Patients that suffer from severe multiple trauma are highly vulnerable to the development of complications that influence their outcomes. Therefore, this study aimed to evaluate the risk factors that can facilitate an early recognition of adult patients at risk. The inclusion criteria were as follows: admission to a level 1 trauma center, injury severity score (ISS) ≥ 16 (severe injury was defined by an abbreviated injury score (AIS) ≥ 3) and ≥18 years of age. Injury- and patient-associated factors were correlated with the development of four complication clusters (surgery-related, infection, thromboembolic events and organ failure) and three mortality time points (immediate (6 h after admission), early (>6 h-72 h) and late (>72 h) mortality). Statistical analysis was performed using a Chi-square, Mann-Whitney U test, Cox hazard regression analysis and binominal logistic regression analysis. In total, 383 patients with a median ISS of 24 (interquartile range (IQR) 17-27) were included. The overall mortality rate (27.4%) peaked in the early mortality group. Lactate on admission significantly correlated with immediate and early mortality. Late mortality was significantly influenced by severe head injuries in patients with a moderate ISS (ISS 16-24). In patients with a high ISS (≥25), late mortality was influenced by a higher ISS, older age and higher rates of organ failure. Complications were observed in 47.5% of all patients, with infections being seen most often. The development of complications was significantly influenced by severe extremity injuries, the duration of mechanical ventilation and length of ICU stay. Infection remains the predominant posttraumatic complication. While immediate and early mortality is mainly influenced by the severity of the initial trauma, the rates of severe head injuries influence late mortality in moderate trauma severity, while organ failure remains a relevant factor in patients with a high injury severity.

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Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients.

Publications

Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients.

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