Use of Metabolomics to Trend Recovery and Therapy After Injury in Critically Ill Trauma Patients

Parent, Brodie; Seaton, Max; Sood, Ravi F.; Gu, Haiwei; Djukovic, Danijel; Raftery, Daniel; O’Keefe, Grant E.

doi:10.1001/jamasurg.2016.0853

Cited by 38 publications

(32 citation statements)

References 34 publications

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“…Targeted HILIC liquid chromatography (LC)-mass spectrometry (MS) metabolite analysis of human plasma samples was performed at the University of Washington Northwest Metabolomics Research Center as previously described. 38, 39 Following a standard protocol, frozen plasma was thawed at 4 °C and a 50 µL aliquot was spiked with a 50 µL mixture containing 22 stable isotope-labeled amino and organic acid internal standards (SILISs) of known concentrations. Methanol (250 µL) containing two SILISs was added and the mixture was vortexed for 10 sec.…”

Section: Methodsmentioning

confidence: 99%

Plasma metabolite abundances are associated with urinary enterolactone excretion in healthy participants on controlled diets

et al. 2017

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Enterolignans, products of gut bacterial metabolism of plant lignans, have been associated with reduced risk of chronic diseases, but their association with other plasma metabolites is unknown. We examined plasma metabolite profiles according to urinary enterolignan excretion in a cross-sectional analysis using data from a randomized crossover, controlled feeding study. Eighty healthy adult males and females completed two 28-day feeding periods differing by glycemic load, refined carbohydrate, and fiber content. Lignan intake was calculated from food records using a polyphenol database. Targeted metabolomics was performed by LC-MS on plasma from fasting blood samples collected at the end of each feeding period. Enterolactone (ENL) and enterodiol (END), were measured in 24-h urine samples collected on the penultimate day of each study period using GC-MS. Linear mixed models were used to test the association between enterolignan excretion and metabolite abundances. Pathway analyses were conducted using the Global Test. Benjamini-Hochberg false discovery rate (FDR) was used to control for multiple testing. Of the metabolites assayed, 121 were detected in all samples. ENL excretion was associated positively with plasma hippuric acid and melatonin, and inversely with epinephrine, creatine, glycochenodeoxycholate, and glyceraldehyde (P <0.05). Hippuric acid only satisfied the FDR of q < 0.1. END excretion was associated with myristic acid and glycine (q <0.5). Two of 57 pathways tested were associated significantly with ENL, ubiquinone and terpenoid-quinone biosynthesis, and inositol phosphate metabolism. These results suggest a potential role for ENL or ENL-metabolizing gut bacteria in regulating plasma metabolites.

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Section: Methodsmentioning

confidence: 99%

Plasma metabolite abundances are associated with urinary enterolactone excretion in healthy participants on controlled diets

et al. 2017

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“…19 Restoration of these antioxidants with EN may be particularly relevant for trauma patients, who generally have ongoing depletion of antioxidant stores over the first week of injury. 11 …”

Section: Discussionmentioning

confidence: 99%

“…As previously described, 10,11,27 the evaluation of metabolic response to nutrition therapy in critically-ill patients is limited by time- and resource-intensive tools like calorimetry and nitrogen-balance studies. With recent innovations in mass-spectrometry-based metabolomics, the biomarkers reported in this study can now be obtained in approximately 3 hours.…”

Section: Discussionmentioning

confidence: 99%

“…Our detailed protocol for sample processing and metabolomics analysis has been previously reported. 11 Briefly, after metabolite extraction, samples underwent targeted liquid chromatography (LC) and quadrupole MS (Sciex 5500 Qtrap), and metabolites were identified by comparison with known standards to obtain relative concentrations. Quality control samples derived from the pooled plasma sample were included in all processing.…”

Section: Methodsmentioning

confidence: 99%

“…10,11 Although calorimetry and nitrogen-balance studies can provide some guidance, these methods are resource- and time- intensive, making them impractical for daily clinical use. 10 …”

Section: Introductionmentioning

confidence: 99%

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Parenteral and enteral nutrition in surgical critical care

Parent

Seaton

Djukovic

et al. 2017

Journal of Trauma and Acute Care Surgery

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Background Artificial nutrition support is central to the care of critically ill patients and is primarily provided enterally (EN). There are circumstances when parenteral nutrition (PN) is considered necessary. We are uncertain how each of these approaches confer clinical benefits beyond simply providing calories. We sought to better understand how each of these techniques influence metabolism in critically-ill patients using a broad-based metabolomics approach. Metabolic responses to EN and PN may differ in ways that could help us understand how to optimize use of these therapies. Methods We prospectively enrolled subjects over 7 months in 2015 at an urban, level-one trauma center. Subjects were included prior to starting either EN or PN during their inpatient admission. Plasma samples were obtained between 1–12 hours before initiation of artificial nutrition, and 3 and 7 days later. All samples were analyzed with liquid chromatography / mass-spectrometry-based metabolomics. Differences in metabolite concentrations were assessed via principal component analyses and multiple linear regression. Results We enrolled 30 subjects. Among the critically-ill subjects, 10 received EN and 10 received PN. In subjects receiving EN, amino acid and urea cycle metabolites (citrulline, p=0.04; ornithine, p=0.05) increased, as did ribonucleic acid metabolites (uridine, p=0.04; cysteine, 0=0.05; oxypurinol, p=0.04). Oxidative stress decreased over time. (increased betaine, p=0.05; decreased 4-pyridoxic acid, p=0.04). In subjects receiving PN amino acid concentrations increased over time (taurine, p=0.04; phenylalanine, p=0.05); omega 6 and omega 3 fatty acid concentrations decreased over time (p=0.05 and 0.03, respectively). Conclusion EN was associated with amino-acid repletion, urea cycle upregulation, restoration of antioxidants, and increasing RNA synthesis. Parenteral nutrition was associated with increased amino acid concentrations, but did not influence protein metabolism or antioxidant repletion. This suggests that parenteral amino acids are utilized less effectively than those given enterally. The biomarkers reported in this study may be useful in guiding nutrition therapy for critically-ill patients. Level of Evidence III, Study Type: Diagnostic Tests or Criteria

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Advances and Promises of Nutritional Influences on Natural Bone Repair

Roberts

Drissi

2019

Journal Orthopaedic Research

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Impaired fracture healing continues to be a significant public health issue. This is more frequently observed in aging populations and patients with co‐morbidities that can directly influence bone repair. Tremendous progress has been made in the development of biologics to enhance and accelerate the healing process; however, side‐effects persist that can cause significant discomfort and tissue damage. This has been the impetus for the development of safe and natural strategies to hasten natural bone healing. Of the many possible approaches, nutrition represents a safe, affordable, and non‐invasive strategy to positively influence each phase of fracture repair. However, our understanding of how healing can be hindered by malnutrition or enhanced with nutritional supplementation has lagged behind the advancements in both surgical management and the knowledge of molecular and cellular drivers of skeletal fracture repair. This review serves to bridge this knowledge gap as well as define the importance of nutrition during fracture healing. The extant literature clearly indicates that pre‐existing nutritional deficiencies should be corrected, and nutritional status should be carefully monitored to prevent the development of malnutrition for the best possible healing outcome. It remains unclear, however, whether the provision of nutrients beyond sufficiency has any benefit on fracture repair and patient outcomes. The combined body of pre‐clinical studies using a variety of animal models suggests a promising role of nutrition as an adjuvant therapy to facilitate fracture repair, but extensive research is needed, specifically at the clinical level, to clarify the utility of nutritional interventions in orthopedics. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:695‐707, 2020

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Use of Metabolomics to Trend Recovery and Therapy After Injury in Critically Ill Trauma Patients

Cited by 38 publications

References 34 publications

Plasma metabolite abundances are associated with urinary enterolactone excretion in healthy participants on controlled diets

Plasma metabolite abundances are associated with urinary enterolactone excretion in healthy participants on controlled diets

Parenteral and enteral nutrition in surgical critical care

Advances and Promises of Nutritional Influences on Natural Bone Repair

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