Dataset Information

Exosome ?-Synuclein Release in Plasma May be Associated With Postoperative Delirium in Hip Fracture Patients.

ABSTRACT: Background: Little is known about the underlying mechanisms of the similarities in the core features of postoperative delirium (POD) and ?-synuclein (?-syn)-related cognitive disorders. We herein investigated associations between fluctuated levels of exosomal ?-syn in the plasma and POD presentation in geriatric hip fracture patients. Methods: We conducted an observational, prospective, and 1:1 matched (on age older than 65, hip fracture diagnosis, American Society of Anesthesiologist' (ASA) physical status, duration of surgery, and intraoperative bleeding) case-control study: POD cases and non-POD controls were selected from the overall cohort by using Confusion Assessment Method (CAM). Delirium severity was measured by the Memorial Delirium Assessment Scale (MDAS). Plasma exosome levels of ?-syn were examined preoperatively and at the time that POD was diagnosed, by using an established immunocapture technology based on a putative brain-cell-specific marker. Circulating concentrations of interleukin-1? (IL-1?), interleukin-6 (IL-6) and tumor necrosis factor-? (TNF-?) were also determined. The relationship between ?-syn levels and POD risk, as well as the association between ?-syn and MDAS scores and plasma cytokines, were assessed. Results: POD incidence was 8.4% (17/202). Postoperative ?-syn were either elevated or lowered. As primary outcome variables, the change of ?-syn in POD patients was significantly higher than non-POD ones (21.0 ± 29.3 pg.ml^-1 vs.1.9 ± 20.0, P = 0.047). The ?-syn alteration was positively correlated to MDAS (r = 0.436, P = 0.010) and the change of IL-6 (r = 0.383, P = 0.025). Conclusions: Exosome ?-syn release in plasma may be associated with the POD development which might be due to systemic inflammation. Clinical Trial Registration: www.clinicaltrials.gov, identifier ChiCTR-IPR-17012301. Prior Presentation: The abstract of this work has been selected for presentation in the 2019 ANESTHESIOLOGY Journal Symposium "What's New with the old," and it has been present in the ASA 2019 annual meeting October 21st, 2019 in Florida.

SUBMITTER: Yuan Y

PROVIDER: S-EPMC7082759 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Exosome α-Synuclein Release in Plasma May be Associated With Postoperative Delirium in Hip Fracture Patients.

Yuan Yi Y Li Zhengqian Z Yang Ning N Han Yongzheng Y Ji Xiaojuan X Han Dengyang D Wang Xiaoxiao X Li Yue Y Liu Taotao T Yuan Feng F He Jindan J Liu Yajie Y Ni Cheng C Zou Peng P Wang Geng G Guo Xiangyang X Zhou Yang Y

Frontiers in aging neuroscience 20200313

<b>Background</b>: Little is known about the underlying mechanisms of the similarities in the core features of postoperative delirium (POD) and α-synuclein (α-syn)-related cognitive disorders. We herein investigated associations between fluctuated levels of exosomal α-syn in the plasma and POD presentation in geriatric hip fracture patients. <b>Methods</b>: We conducted an observational, prospective, and 1:1 matched (on age older than 65, hip fracture diagnosis, American Society of Anesthesiolog ...[more]

PMID: 32231560

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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:BackgroundPost-hip fracture surgery delirium (PHFD) is a significant clinical problem in older patients, but an adequate, simple risk prediction model for use in the preoperative period has not been developed.MethodsThe 2016 American College of Surgeons National Surgical Quality Improvement Program Hip Fracture Procedure Targeted Participant Use Data File was used to obtain a cohort of patients ≥60 years of age who underwent hip fracture surgery (n = 8871; randomly assigned to derivation [70%] or validation [30%] cohorts). A parsimonious prediction model for PHFD was developed in the derivation cohort using stepwise multivariable logistic regression with further removal of variables by evaluating changes in the area under the receiver operator characteristic curve (AUC). A risk score was developed from the final multivariable model.ResultsOf 6210 patients in the derivation cohort, PHFD occurred in 1816 (29.2%). Of 32 candidate variables, 9 were included in the final model: (1) preoperative delirium (adjusted odds ratio [aOR], 8.32 [95% confidence interval {CI}, 6.78-10.21], 8 risk score points); (2) preoperative dementia (aOR, 2.38 [95% CI, 2.05-2.76], 3 points); (3) age (reference, 60-69 years of age) (age 70-79: aOR, 1.60 [95% CI, 1.20-2.12], 2 points; age 80-89: aOR, 2.09 [95% CI, 1.59-2.74], 2 points; and age ≥90: aOR, 2.43 [95% CI, 1.82-3.23], 3 points); (4) medical comanagement (aOR, 1.43 [95% CI, 1.13-1.81], 1 point); (5) American Society of Anesthesiologists (ASA) physical status III-V (aOR, 1.40 [95% CI, 1.14-1.73], 1 point); (6) functional dependence (aOR, 1.37 [95% CI, 1.17-1.61], 1 point); (7) smoking (aOR, 1.36 [95% CI, 1.07-1.72], 1 point); (8) systemic inflammatory response syndrome/sepsis/septic shock (aOR, 1.34 [95% CI, 1.09-1.65], 1 point); and (9) preoperative use of mobility aid (aOR, 1.32 [95% CI, 1.14-1.52], 1 point), resulting in a risk score ranging from 0 to 20 points. The AUCs of the logistic regression and risk score models were 0.77 (95% CI, 0.76-0.78) and 0.77 (95% CI, 0.76-0.78), respectively, with similar results in the validation cohort.ConclusionsA risk score based on 9 preoperative risk factors can predict PHFD in older adult patients with fairly good accuracy.

Project description:ObjectiveTo 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 methodsThis 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.ResultsDemographic 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.ConclusionMultiple 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 registrationwww.ClinicalTrials.gov, identifier ChiCTR1900021533.

Project description:While delirium is associated with cognitive decline and dementia, there is limited evidence to support causality for this relationship. Clarification of how delirium may cause cognitive decline, perhaps through evidence of contemporaneous neuronal injury, would enhance plausibility for a causal relationship. Dose-dependence of neuronal injury with delirium severity would further enhance the biological plausibility for this relationship. We tested whether delirium is associated with neuronal injury in 114 surgical patients recruited to a prospective biomarker cohort study. Patients underwent perioperative testing for changes in neurofilament light, a neuronal injury biomarker, as well as a panel of 10 cytokines, with contemporaneous assessment of delirium severity and incidence. A subset of patients underwent preoperative MRI. Initially we confirmed prior reports that neurofilament light levels correlated with markers of neurodegeneration [hippocampal volume (ΔR2 = 0.129, P = 0.015)] and white matter changes including fractional anisotropy of white matter (ΔR2 = 0.417, P < 0.001) with similar effects on mean, axial and radial diffusivity) in our cohort and that surgery was associated with increasing neurofilament light from preoperative levels [mean difference (95% confidence interval, CI) = 0.240 (0.178, 0.301) log10 (pg/ml), P < 0.001], suggesting putative neuronal injury. Next, we tested the relationship with delirium. Neurofilament light rose more sharply in participants with delirium compared to non-sufferers [mean difference (95% CI) = 0.251 (0.136, 0.367) log10 (pg/ml), P < 0.001]. This relationship showed dose-dependence, such that neurofilament light rose proportionately to delirium severity (ΔR2 = 0.199, P < 0.001). Given that inflammation is considered an important driver of postoperative delirium, next we tested whether neurofilament light, as a potential marker of neurotoxicity, may contribute to the pathogenesis of delirium independent of inflammation. From a panel of 10 cytokines, the pro-inflammatory cytokine IL-8 exhibited a strong correlation with delirium severity (ΔR2 = 0.208, P < 0.001). Therefore, we tested whether the change in neurofilament light contributed to delirium severity independent of IL-8. Neurofilament light was independently associated with delirium severity after adjusting for the change in inflammation (ΔR2 = 0.040, P = 0.038). These data suggest delirium is associated with exaggerated increases in neurofilament light and that this putative neurotoxicity may contribute to the pathogenesis of delirium itself, independent of changes in inflammation.

Dataset Information

Exosome ?-Synuclein Release in Plasma May be Associated With Postoperative Delirium in Hip Fracture Patients.

Publications

Exosome α-Synuclein Release in Plasma May be Associated With Postoperative Delirium in Hip Fracture Patients.

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