Serum Metabolic Profiles Based on Nuclear Magnetic Resonance Spectroscopy among Patients with Deep Vein Thrombosis and Healthy Controls

Quintero, Melissa; Tasić, Ljubica; Costa, Tássia Brena Barroso Carneiro; Stanisić, Danijela; Montalvão, Silmara Aparecida de Lima; Huber, Stephany Cares; Annichino‐Bizzacchi, Joyce Maria

doi:10.3390/metabo11120874

Cited by 8 publications

(19 citation statements)

References 45 publications

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“…21 Conversely, a study of serum metabolic profiles based on nuclear magnetic resonance spectroscopy in patients with deep vein thrombosis and healthy controls showed significant reductions in leucine, valine and alanine concentrations in the thrombosis group. 22 In view of the conclusions of the above studies and the heterogeneity of arterial and venous thrombosis, we inferred that these BCAAs are potential biomarkers of CVT.…”

Section: Discussionmentioning

confidence: 81%

Potential role of plasma branched-chain amino acids in the differential diagnosis of acute cerebral venous thrombosis

Jiang

Zhou

Wei

et al. 2023

J Cereb Blood Flow Metab

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Cerebral venous thrombosis (CVT) is a special and easily misdiagnosed or undiagnosed subtype of stroke. To identify specific biomarkers with a high predictive ability for the diagnosis of acute CVT, we performed metabolomic analysis in plasma samples from acute CVT patients and healthy controls and confirmed the results in validation cohorts. In the discovery stage, there were 343 differential metabolites, and the caffeine metabolism pathway and the biosynthesis pathway for the branched chain amino acids (BCAAs) valine, leucine, and isoleucine were two significant pathways between the CVT and healthy cohorts. The area under the curve (AUC) for metabolites associated with valine, leucine, and isoleucine biosynthesis was 0.934. In the validation stage, the BCAA concentrations demonstrated an AUC of 0.935 to differentiate patients with acute CVT from the control cohort. In addition, BCAAs combined with D-dimer levels were used to establish a diagnostic model for CVT, and the AUC was 0.951, showing good diagnostic efficacy of separating CVT patients from the control cohort. BCAAs as plasma biomarkers deserve to be further studied and even developed in clinical CVT management.

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Section: Discussionmentioning

confidence: 81%

Potential role of plasma branched-chain amino acids in the differential diagnosis of acute cerebral venous thrombosis

Jiang

Zhou

Wei

et al. 2023

J Cereb Blood Flow Metab

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“…Limited literature is available for comparison with the findings of the current study. Among the top 20 metabolites, only EPA and isoleucine have been reported to be associated with thrombosis 18 . However, contrary to an earlier report that EPA is linked to reduced risk of thrombosis, EPA was associated with increased risk of thrombosis in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Wang et al showed that the metabolite trimethylamine N-oxide (TMAO) was associated with future risk of atherosclerotic events, and they discovered a novel link between the gut-flora-dependent metabolism of dietary phosphatidylcholine and cardiovascular pathogenesis 13 . So far, few studies have used metabolomics technology to explore the etiology of thrombosis [14][15][16][17][18] , and no studies have used the platform to examine thrombosis after surgery in children with CHD. In this study, we aimed to identify novel metabolites and metabolic pathways that are associated with the development of thrombosis after cardiac surgery in children with CHD.…”

Section: Introductionmentioning

confidence: 99%

A Metabolomics Study of Thrombosis after Cardiac Surgery in Children with Congenital Heart Disease

Watson

Jorgenson

et al. 2023

Preprint

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Objective: Thrombosis is a major complication after cardiac surgery in children with congenital heart disease (CHD). The mechanisms underlying thrombosis development remain poorly understood. We aimed to identify novel circulating metabolites before cardiac surgery that are associated with the development of thrombosis after surgery in children with CHD. Approach and Results: All blood samples were drawn right before surgical incision and after the induction of anesthesia, and plasma was separated immediately under 4 °C. Untargeted metabolomic data were measured by Metabolon in plasma from children (age range: 0 days-18 years) with CHD undergoing cardiac surgery. The primary outcome was thrombosis within 30 days of surgery or before discharge. Associations of individual metabolites with thrombosis were assessed with logistic regression with false discovery rate (FDR) correction for multiple comparison and adjustment for clinical characteristics; elastic net regression was used to select a prediction model. Out of 1,115 metabolites measured in samples from 203 children, 776 met the quality control criteria. In total, 26 children (12.8%) developed thrombosis. Among the 776 metabolites, 195 were significantly associated with thrombosis (FDR q-value < 0.05). The top three metabolites showing the strongest associations with thrombosis were eicosapentaenoate, steroid monosulfate C19H28O6S, and formiminoglutamate (FDR = 0.01 for all). Pathway analysis showed that the pathways of nicotinate and nicotinamide metabolism (P = 0.0007) and glycerophospholipid metabolism (P = 0.002) were enriched and had significant impacts on the development of thrombosis. In elastic net regression analysis, the area under the receiver operating-characteristic curve of a prediction model for thrombosis was 0.94 in the training sample (70% of the total sample) and 0.84 in the testing sample (the remaining 30%). Conclusion: We have identified promising novel metabolites and metabolic pathways associated with thrombosis. Future studies are warranted to confirm the findings and examine the mechanistic pathways to thrombosis.

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“…Previous studies identified metabolomic biomarkers for neurodegenerative disorders, but human metabolomic studies of tinnitus are lacking. A study in rats identified perturbations in several metabolic pathways with tinnitus, and multiple metabolite alterations demonstrated in brain tissue were also demonstrated in plasma .…”

Section: Introductionmentioning

confidence: 99%

Association of Plasma Metabolomic Biomarkers With Persistent Tinnitus

Zeleznik

Welling

Stanković

et al. 2023

JAMA Otolaryngol Head Neck Surg

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ImportancePersistent tinnitus is common, disabling, and difficult to treat.ObjectiveTo evaluate the association between circulating metabolites and persistent tinnitus.Design, Setting, and ParticipantsThis was a population-based case-control study of 6477 women who were participants in the Nurses’ Health Study (NHS) and NHS II with metabolomic profiles and tinnitus data. Information on tinnitus onset and frequency was collected on biennial questionnaires (2009-2017). For cases, metabolomic profiles were measured (2015-2021) in blood samples collected after the date of the participant’s first report of persistent tinnitus (NHS, 1989-1999 and 2010-2012; NHS II, 1996-1999). Data analyses were performed from January 24, 2022, to January 14, 2023.ExposuresIn total, 466 plasma metabolites from 488 cases of persistent tinnitus and 5989 controls were profiled using 3 complementary liquid chromatography tandem mass spectrometry approaches.Main Outcomes and MeasuresLogistic regression was used to estimate odds ratios (ORs) of persistent tinnitus (per 1 SD increase in metabolite values) and 95% CIs for each individual metabolite. Metabolite set enrichment analysis was used to identify metabolite classes enriched for associations with tinnitus.ResultsOf the 6477 study participants (mean [SD] age, 52 [9] years; 6477 [100%] female; 6121 [95%] White individuals) who were registered nurses, 488 reported experiencing daily persistent (≥5 minutes) tinnitus. Compared with participants with no tinnitus (5989 controls), those with persistent tinnitus were slightly older (53.0 vs 51.8 years) and more likely to be postmenopausal, using oral postmenopausal hormone therapy, and have type 2 diabetes, hypertension, and/or hearing loss at baseline. Compared with controls, homocitrulline (OR, 1.32; (95% CI, 1.16-1.50); C38:6 phosphatidylethanolamine (PE; OR, 1.24; 95% CIs, 1.12-1.38), C52:6 triglyceride (TAG; OR, 1.22; 95% CIs, 1.10-1.36), C36:4 PE (OR, 1.22; 95% CIs, 1.10-1.35), C40:6 PE (OR, 1.22; 95% CIs, 1.09-1.35), and C56:7 TAG (OR, 1.21; 95% CIs, 1.09-1.34) were positively associated, whereas α-keto-β-methylvalerate (OR, 0.68; 95% CIs, 0.56-0.82) and levulinate (OR, 0.60; 95% CIs, 0.46-0.79) were inversely associated with persistent tinnitus. Among metabolite classes, TAGs (normalized enrichment score [NES], 2.68), PEs (NES, 2.48), and diglycerides (NES, 1.65) were positively associated, whereas phosphatidylcholine plasmalogens (NES, −1.91), lysophosphatidylcholines (NES, −2.23), and cholesteryl esters (NES,−2.31) were inversely associated with persistent tinnitus.Conclusions and RelevanceThis population-based case-control study of metabolomic profiles and tinnitus identified novel plasma metabolites and metabolite classes that were significantly associated with persistent tinnitus, suggesting that metabolomic studies may help improve understanding of tinnitus pathophysiology and identify therapeutic targets for this challenging disorder.

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Serum Metabolic Profiles Based on Nuclear Magnetic Resonance Spectroscopy among Patients with Deep Vein Thrombosis and Healthy Controls

Cited by 8 publications

References 45 publications

Potential role of plasma branched-chain amino acids in the differential diagnosis of acute cerebral venous thrombosis

Potential role of plasma branched-chain amino acids in the differential diagnosis of acute cerebral venous thrombosis

A Metabolomics Study of Thrombosis after Cardiac Surgery in Children with Congenital Heart Disease

Association of Plasma Metabolomic Biomarkers With Persistent Tinnitus

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