1H NMR Urinary Metabolomic Analysis in Older Adults after Hip Fracture Surgery May Provide Valuable Information for Patient Profiling-A Preliminary Investigation.

In these times of precision and personalized medicine, profiling patients to identify their needs is crucial to providing the best and most cost-effective treatment. In this study, we used urine metabolomics to explore the characterization of older adults with hip fractures and to explore the forecasting of patient outcomes. Overnight urine specimens were collected from 33 patients (mean age 80 ± 8 years) after hip fracture surgery during their stay at a rehabilitation hospital. The specimens were analyzed with 1H NMR spectroscopy. We performed a metabolomics study regarding assessments of frailty status, Functional Independence Measure (FIM), and Short Physical Performance Battery (SPPB). The main metabolic variations concerned 10 identified metabolites: paracetamol derivatives (4 peaks: 2.15 ppm; 2.16 ppm; 7.13 ppm and 7.15 ppm); hippuric acid; acetate; acetone; dimethylamine; glycine; alanine; lactate; valine; TMAO. At baseline, the urinary levels of these metabolites were significantly higher (i) in frail compared with non-frail patients, (ii) in persons with poorer FIM scores, and (iii) in persons with poorer compared SPPB scores. Our findings suggested that patients with increased levels of urine metabolites associated with metabolic, inflammatory, and renal disorders presented clear signs of frailty, impaired functional independence, and poor physical performance. Metabolomics could be a valuable tool to further characterize older adults, especially after major medical events.

1H-NMR-Based Analysis for Exploring Knee Synovial Fluid Metabolite Changes after Local Cryotherapy in Knee Arthritis Patients.

Rehabilitation using cryotherapy has widely been used in inflammatory diseases to relieve pain and decrease the disease activity. The aim of this study was to explore the metabolite changes in inflammatory knee-joint synovial fluids following local cryotherapy treatment (ice or cold CO2). We used proton nuclear magnetic resonance (1H NMR) spectroscopy to assess the metabolite patterns in synovial fluid (SF) in patients with knee arthritis (n = 46) before (D0) and after (D1, 24 h later) two applications of local cryotherapy. Spectra from aqueous samples and organic extracts were obtained with an 11.75 Tesla spectrometer. The metabolite concentrations within the SF were compared between D1 and D0 using multiple comparisons with the application of a false discovery rate (FDR) adjusted at 10% for each metabolite. A total of 32 metabolites/chemical structures were identified including amino acids, organic acids, fatty acids or sugars. Pyruvate, alanine, citrate, threonine was significantly higher at D1 vs D0 (p < 0.05). Tyrosine concentration significantly decreases after cryotherapy application (p < 0.001). We did not observe any effect of gender and cooling technique on metabolite concentrations between D0 and D1 (p > 0.05). The present study provides new insight into a short-term effect of cold stimulus in synovial fluid from patients with knee arthritis. Our observations suggest that the increased level of metabolites involved in energy metabolism may explain the underlying molecular pathways that mediate the antioxidant and anti-inflammatory capacities of cryotherapy.

Analysis of perfusates during hypothermic machine perfusion by NMR spectroscopy: a potential tool for predicting kidney graft outcome.

BACKGROUND: Machine perfusion use has been reported to promote graft outcome in case of donation after cardiac death. Our objective was to evaluate the potential for nuclear magnetic resonance (NMR) to predict graft outcome by analyzing perfusates during machine perfusion time. METHOD: We used a renal autotransplantation model mimicking deceased after cardiac death donors with pigs. Organs were subjected to 60 min of warm ischemia before the hypothermic machine preservation during 22 hr. We studied the correlation between creatinemia after transplantation and the NMR data from perfusates. RESULTS: A metabonomic analysis allowed us to highlight the evolution of several metabolites during perfusion: the concentration of lactate, choline, or amino acids such as valine, glycine, or glutamate increased with time, whereas there was a diminution of total glutathione during this period. The changes in these biomarkers were less severe in the group with the better outcome. Statistical analysis revealed a strong association between the level of those metabolites during machine perfusion and function recovery (Spearman rank ≥0.89; P<0.05). CONCLUSION: Multivariate analysis of lesion biomarkers during kidney perfusion using NMR data could be an interesting tool to assess graft quality, particularly because analyses times (2 hr total) are compatible with clinical application.

Elevated CSF N-acetylaspartylglutamate suggests specific molecular diagnostic abnormalities in patients with white matter diseases.

BACKGROUND: In order to identify biomarkers useful for the diagnosis of genetic white matter disorders we compared the metabolic profile of patients with leukodystrophies with a hypomyelinating or a non-hypomyelinating MRI pattern. METHODS: We used a non-a priori method of in vitro ¹H-NMR spectroscopy on CSF samples of 74 patients with leukodystrophies. RESULTS: We found an elevation of CSF N-acetylaspartylglutamate (NAAG) in patients with Pelizaeus-Merzbacher disease (PMD)-PLP1 gene, Pelizaeus-Merzbacher-like disease-GJC2 gene and Canavan disease-ASPA gene. In the PMD group, NAAG was significantly elevated in the CSF of all patients with PLP1 duplication (19/19) but was strictly normal in 6 out of 7 patients with PLP1 point mutations. Additionally, we previously reported increased CSF NAAG in patients with SLC17A5 mutations. CONCLUSIONS: Elevated CSF NAAG is a biomarker that suggests specific molecular diagnostic abnormalities in patients with white matter diseases. Our findings also point to unique pathological functions of the overexpressed PLP in PMD patients with duplication of this gene.