Dataset Information

Cerebrospinal Fluid Spermidine, Glutamine and Putrescine Predict Postoperative Delirium Following Elective Orthopaedic Surgery.

ABSTRACT: Delirium is a marker of brain vulnerability, associated with increasing age, pre-existing cognitive impairment and, recently, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease. This nested case-control study used a targeted quantitative metabolomic methodology to profile the preoperative CSF of patients (n?=?54) who developed delirium following arthroplasty (n?=?28) and those who did not (n?=?26). The aim was to identify novel preoperative markers of delirium, and to assess potential correlations with clinical data. Participants without a diagnosis of dementia (?65 years) undergoing elective primary hip or knee arthroplasty were postoperatively assessed for delirium once-daily for three days. Groups were compared using multivariate, univariate and receiving operator characteristic (ROC) methods. Multivariate modelling using Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) of metabolomic data readily distinguished between delirium and control groups (R2???0.56; Q2???0.10). Three metabolites (spermidine, putrescine and glutamine) significantly differed between groups (P??0.75). The biomarker performance of the two polyamines (spermidine/putrescine) was enhanced by ratio with CSF A?42 (ROC?>?0.8), and spermidine significantly correlated with A?42 (pearson r?=?-0.32; P?=?0.018). These findings suggest that spermidine and putrescine levels could be useful markers of postoperative delirium risk, particularly when combined with A?42, and this requires further investigation.

SUBMITTER: Pan X

PROVIDER: S-EPMC6414730 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Cerebrospinal Fluid Spermidine, Glutamine and Putrescine Predict Postoperative Delirium Following Elective Orthopaedic Surgery.

Pan Xiaobei X Cunningham Emma L EL Passmore Anthony P AP McGuinness Bernadette B McAuley Daniel F DF Beverland David D O'Brien Seamus S Mawhinney Tim T Schott Jonathan M JM Zetterberg Henrik H Green Brian D BD

Scientific reports 20190312 1

Delirium is a marker of brain vulnerability, associated with increasing age, pre-existing cognitive impairment and, recently, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease. This nested case-control study used a targeted quantitative metabolomic methodology to profile the preoperative CSF of patients (n = 54) who developed delirium following arthroplasty (n = 28) and those who did not (n = 26). The aim was to identify novel preoperative markers of delirium, and to assess potential c ...[more]

PMID: 30862889

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Project description:Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with development of postoperative delirium in older surgical patients. We employed a nested case–control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p<0.05). Due to the limited sample size these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identifies 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.

Project description:Delirium is a common, morbid, and costly postoperative complication. We aimed to identify blood-based postoperative delirium markers in a nested case-control study of older surgical patients using a proteomics approach followed by enzyme-linked immunosorbent assay (ELISA) validation.The Successful Aging after Elective Surgery study enrolled dementia-free adults ?70 years old undergoing major scheduled noncardiac surgery (N = 566; 24% delirium). Plasma was collected at four time points: preoperative, postanesthesia care unit, postoperative day 2, and 1 month postoperative. Matched pairs were selected for the independent discovery (39 pairs) and replication cohorts (36 pairs), which were subsequently combined into the pooled cohort (75 pairs). Isobaric tags for relative and absolute quantitation-based relative quantitation mass spectrometry proteomics were performed to identify the strongest delirium-related protein, which was selected for ELISA validation. Using the ELISA results, statistical analyses using nonparametric signed rank tests were performed in all cohorts examining the association between the identified protein and delirium.C-reactive protein emerged from the proteomics analysis as the strongest delirium-related protein. Validation by ELISA confirmed that compared with controls, cases had significantly higher C-reactive protein levels in the discovery, replication, and pooled cohorts at the preoperative (median paired difference [MPD] 1.97 mg/L [p < .05], 0.29 mg/L, 1.56 mg/L [p < .01]), postanesthesia care unit (MPD 2.83 mg/L, 2.22 mg/L [p < .05], 2.53 mg/L [p < .01]) and postoperative day 2 (MPD 71.97 mg/L [p < .01], 35.18 mg/L [p < .05], 63.76 mg/L [p < .01]) time points, but not 1 month postoperative (MPD 2.72 mg/L, -0.66 mg/L, 1.10 mg/L).Elevated preoperative and postoperative plasma levels of C-reactive protein were associated with delirium, suggesting that a preinflammatory state and heightened inflammatory response to surgery are potential pathophysiologic mechanisms of delirium.

Dataset Information

Cerebrospinal Fluid Spermidine, Glutamine and Putrescine Predict Postoperative Delirium Following Elective Orthopaedic Surgery.

Publications

Cerebrospinal Fluid Spermidine, Glutamine and Putrescine Predict Postoperative Delirium Following Elective Orthopaedic Surgery.

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