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Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium.

ABSTRACT: Objective:To investigate dysregulated molecules in preoperative cerebrospinal fluid (CSF) of elderly hip fracture patients with postoperative delirium (POD), in order to identify potential pathological mechanisms and biomarkers for pre-stage POD. Materials and Methods:This nested case control study used untargeted metabolomic and lipidomic analysis to profile the preoperative CSF of patients (n = 40) who developed POD undergone hip fracture surgery (n = 10) and those who did not (n = 30). Thirty Non-POD patients were matched to 10 POD patients by age (± 2 years) and Mini Mental State Examination score (± 2 points). CSF was collected after successful spinal anesthesia and banked for subsequent analysis. On the first two postoperative days, patients were assessed twice daily using the Confusion Assessment Method-Chinese Revision. CSF samples from the two groups were analyzed to investigate possible relevant pathological mechanisms and identify candidate biomarkers. Results:Demographic characteristics of the groups were matched. Eighteen metabolites and thirty-three lipids were dysregulated in the preoperative CSF of POD patients. Pathway enrichment analysis revealed perturbations in D-glutamine and D-glutamate metabolism; glycerophospholipid metabolism; alanine, aspartate and glutamate metabolism; sphingolipid metabolism; histidine metabolism; and arginine biosynthesis at the pre-delirium stage. Receiver operating characteristic curve analysis indicated that phosphatidylethanolamine (PE, 40:7e), with an area under the curve value of 0.92, is a potential biomarker for POD. Conclusion:Multiple pathological mechanisms in the POD group were involved before surgery, including neuroinflammation, oxidative stress, and energy metabolism disorders induced by hypoxia, as well as neurotransmitter imbalances such as increased dopamine and glutamate, and decreased glutamine. These metabolic abnormalities potentially increase the fragility of the brain, thus contributing to POD. PE (40:7e) might be a potential biomarker for POD. Not only do our results provide potential biomarkers for POD, but also provide information for deep pathological research. Clinical Trial Registration:www.ClinicalTrials.gov, identifier ChiCTR1900021533.

SUBMITTER: Han Y

PROVIDER: S-EPMC7642614 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium.

Han Yongzheng Y Zhang Wenchao W Liu Jiao J Song Yanan Y Liu Taotao T Li Zhengqian Z Wang Xiaoxiao X Yang Ning N Li Yue Y Han Dengyang D Mi Xinning X Zhou Yang Y Li Min M Guo Xiangyang X Zhong Lijun L Wang Geng G Yuan Yi Y

Frontiers in aging neuroscience 20201022

<h4>Objective</h4>To investigate dysregulated molecules in preoperative cerebrospinal fluid (CSF) of elderly hip fracture patients with postoperative delirium (POD), in order to identify potential pathological mechanisms and biomarkers for pre-stage POD.<h4>Materials and methods</h4>This nested case control study used untargeted metabolomic and lipidomic analysis to profile the preoperative CSF of patients (<i>n</i> = 40) who developed POD undergone hip fracture surgery (<i>n</i> = 10) and those ...[more]

PMID: 33192460

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Project description:ObjectiveThis study aims to examine the association between preoperative serum albumin levels and postoperative delirium (POD) in geriatric patients who have undergone hip fracture surgery, with the goal of offering novel insights for clinical interventions targeting POD.MethodsA retrospective analysis was conducted on the medical records of patients who underwent hip fracture surgery in a tertiary medical institution from January 2013 to November 2023. The patients were classified based on hypoalbuminemia (defined as a serum albumin level < 35 g/L) and clinical threshold. Multivariable logistic regression and propensity score matching analysis (PSM) were employed to calculate the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for POD to eliminate potential confounding factors. Additionally, subgroup analysis was performed to explore the interaction effect.ResultsThe retrospective cohort study included 1,440 patients, with an incidence of POD found to be 19.1%. In a multivariable logistic regression analysis, patients with hypoalbuminemia had an adjusted OR of 2.99 (95%CI: 2.14-4.18) compared to those with normal albumin levels (≥ 35 g/L). Furthermore, a significant trend was observed across different severity categories, including mild hypoalbuminemia (34.9-30.0 g/L; adjusted OR = 2.71, 95%CI: 1.84-3.99), moderate hypoalbuminemia (29.9-25.0 g/L, adjusted OR = 3.44, 95%CI: 1.88-6.28), and severe hypoalbuminemia (<25.0 g/L; adjusted OR = 3.97, 95%CI: 1.78-8.86), with a trend value of p <0.001. Similar results were observed in the PSM analysis. Additionally, treating preoperative serum albumin level as a continuous variable, the risk of POD increased by 11% (95% CI, 1.08-1.15) with each 1 g/L decrease in preoperative serum albumin level.ConclusionLow preoperative levels of albumin are strongly associated with POD in geriatric patients with hip fractures, and a significant dose-response relationship exists between them.

Project description:Objective: To analyze the proteome of preoperative cerebrospinal fluid (CSF) in older orthopedic patients with or without postoperative delirium (POD) using untargeted proteomics. Methods: A prospective cohort study was conducted. Eighty hip fracture patients aged ≥65 years were recruited. After successful spinal anesthesia, CSF was collected. The patients were divided into POD and No-POD groups based on the Confusion Assessment Method, and patients with POD were graded using the Memorial Delirium Assessment Scale (MDAS). Thirty No-POD patients were matched to 10 POD patients by age (±2 years) and Mini-Mental State Examination score (±2 scores). Label-free proteomic analysis was performed using a liquid chromatography coupled to mass spectrometry (LC-MS) workflow. Validation was performed using mass-spectrometry-based parallel reaction monitoring (PRM) for the 30 No-POD and 10 POD patients, as well as for an additional 5 POD patients. Bioinformatics were used to investigate possible relevant pathological mechanisms. Results: The incidence of POD in older orthopedic patients was 18.8% in our cohort of 80 patients. Proteomics results revealed 63 dysregulated CSF proteins, and PRM analysis validated these results. The preoperative CSF levels of both V-set and transmembrane domain-containing protein 2B (VSTM2B) and coagulation factor V (FA5) were positively correlated with MDAS scores on postoperative day 1 (r > 0.8, p < 0.05). Bioinformatic analysis revealed that several nervous-system-related pathways are relevant to POD development. Conclusion: We identified and validated several novel CSF proteins that are dysregulated in POD, and revealed several pathways that are relevant to POD development. Our results not only provide risk biomarkers for POD, but also give clues for further investigations into the pathological mechanisms of delirium. Clinical trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR1900021533).

Project description:ObjectiveOlder patients with hip fractures who are undergoing surgery are at high risk of significant mortality and morbidity including postoperative delirium. It is unclear whether different types of anaesthesia may reduce the incidence of postoperative delirium. This systematic review will investigate the impact of anaesthetic technique on postoperative delirium. Other outcomes included mortality, length of stay, complications and functional outcomes.DesignSystematic review of randomised controlled trials and non-randomised controlled studies.Data sourcesBibliographic databases were searched from inception to June 2018. Web of Science and ZETOC databases were searched for conference proceedings. Reference lists of relevant articles were checked, and clinical trial registers were searched to identify ongoing trials.Eligibility criteriaStudies were eligible if general and regional anaesthesia were compared in patients (aged 60 and over) undergoing hip fracture surgery, reporting primary outcome of postoperative delirium and secondary outcomes of mortality, length of hospital stay, adverse events, functional outcomes, discharge location and quality of life. Exclusion criteria were anaesthetic technique or drug not considered current standard practice; patients undergoing hip fracture surgery alongside other surgery and uncontrolled studies.ResultsOne hundred and four studies were included. There was no evidence to suggest that anaesthesia type influences postoperative delirium or mortality. Some studies suggested a small reduction in length of hospital stay with regional anaesthesia. There was some evidence to suggest that respiratory complications and intraoperative hypotension were more common with general anaesthesia. Heterogeneity precluded meta-analysis. All findings were described narratively and data were presented where possible in forest plots for illustrative purposes.ConclusionsWhile there was no evidence to suggest that anaesthesia types influence postoperative delirium, the evidence base is lacking. There is a need to ascertain the impact of type of anaesthesia on outcomes with an adequately powered, methodologically rigorous study.Prospero registration numberCRD42015020166.

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Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium.

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Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium.

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