Tau as a serum biomarker of delirium after major cardiac surgery: a single centre case-control study.
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ABSTRACT:
SUBMITTER: McKay TB
PROVIDER: S-EPMC9428914 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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Tau as a serum biomarker of delirium after major cardiac surgery: a single centre case-control study.
McKay Tina B TB Qu Jason J Liang Feng F Mueller Ariel A Wiener-Kronish Jeanine J Xie Zhongcong Z Akeju Oluwaseun O
British journal of anaesthesia 20220422 1
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Project description:ObjectivesThe objective of this study was to identify novel serum biomarkers specific to postoperative delirium after major cardiac surgery to provide insight into the pathologic processes involved in delirium and its sequelae.DesignNested, case-control study.SettingCardiac surgical intensive care unit in a single-site hospital setting.ParticipantsThe study comprised 24 older adults (aged >60 years) undergoing major cardiac surgery with cardiopulmonary bypass.InterventionsNone.Measurements and main resultsThe primary outcome was a positive screen for delirium from postoperative days one through three based on criteria included in the long form of the Confusion Assessment Method. A multiplexed proteomic approach was applied using proximity extension assays to identify and quantify proteins found in serum collected on the day of surgery and postoperative day one in delirious and nondelirious patient cohorts. An increase in serum fibroblast growth factor (FGF)-21 levels was identified in the delirious cohort from a presurgery baseline of (mean ± standard deviation) 5.0 ± 1.1 log2 abundance (95% confidence interval [CI], 4.3-5.7) to 6.7 ± 1.6 log2 abundance (95% CI, 5.7-7.7; p = 0.01) postsurgery. A similar increase was identified in FGF-23 from a presurgery baseline of 1.7 ± 1.3 log2 abundance (95% CI, 0.8-2.5) to 3.4 ± 2.2 log2 abundance (95% CI, 2.0-4.8; p = 0.06) postsurgery. An increase in interleukin-6 serum levels also was identified in the delirious cohort from a presurgery baseline of 3.8 ± 1.1 log2 abundance (95% CI, 3.1-4.5) to 8.7 ± 1.9 log2 abundance (95% CI, 7.5-9.9; p < 0.0001) postsurgery. However, the increase in interleukin-6 serum levels of the nondelirious cohort also met the study's threshold for statistical significance (p < 0.0001). Finally, an increase in monocyte chemotactic protein-3 serum levels was identified in the delirious cohort from a presurgery baseline of 4.1 ± 0.9 log2 abundance (95% CI, 3.6-4.7) to 6.1 ± 2.0 log2 abundance (95% CI, 4.8-7; p = 0.009) postsurgery.ConclusionsFGF-21, FGF-23, interleukin-6, and monocyte chemotactic protein-3 serum levels were increased postoperatively in patients who developed delirium after major cardiac surgery. This study identified two members of the FGF family as potential putative systemic biomarkers for postoperative delirium after cardiac surgery, suggesting a possible role for metabolic recovery in the pathophysiologic mechanisms underlying neurocognitive dysfunction.
| S-EPMC8586054 | biostudies-literature
Project description:BackgroundThe association between hypernatremia and delirium after cardiac surgery has rarely been investigated. This study aimed to determine whether hypernatremia increases the risk of delirium after exposure.Materials and methodsFrom April 2016 to June 2021, 7,831 consecutive patients receiving cardiac surgery were screened for potential enrollment. The primary outcome was postoperative delirium (POD). For the respective case of delirium, 10 controls were matched according to the index date within the nested case-control design. Hypernatremia exposure was defined as serum sodium > 145 mmol/L within 7 days before the index date. A generalized estimation equation was performed to assess excess risks for POD associated with hypernatremia, adjusted for demographics and clinical variables.ResultsAbout 7,277 patients were included in the final analyses. About 669 (9.2%) patients with POD were assigned to the case group, and 6,690 controls were identified from the whole population. About 66.5% of the cases and 36.3% of the controls had hypernatremia exposure. After being adjusted to certain well-recognized confounding factors, hypernatremia showed a significant correlation with increased risk of delirium after cardiac surgery (adjusted OR, 1.73; 95% CI, 1.41~2.12). An e-value analysis suggested the robustness to unmeasured confounding.ConclusionsHypernatremia was associated with an increased risk of delirium after cardiac surgery. This finding could have implications for risk stratification, early detection, and management of delirium in patients receiving cardiac surgery.
| S-EPMC8959150 | biostudies-literature
Project description:BackgroundPostoperative delirium (POD) is an acute altered mental state commonly encountered after cardiac surgery. The pathophysiological mechanisms underlying POD remain unclear. We aimed to identify circulating proteins significantly altered after major cardiac surgery with cardiopulmonary bypass (CPB). We also aimed to enable inferences on associations with POD.MethodsSerum and whole blood samples were collected before CPB (n = 16 patients; n = 8 with POD) and again from the same patients on postoperative day 1. All patients were clinically evaluated for POD on postoperative days 1-3. An aptamer-based proteomics platform (SOMAscan) was used to quantify serum protein abundance in patients with POD compared with non-POD controls. We also performed a lipopolysaccharide (LPS)-based in vitro functional analysis (TruCulture) on whole blood samples from patients with POD and non-POD controls to approximate surgical stress. Cytokine levels were determined using a Luminex immunoassay.ResultsCardiac surgery with CPB resulted in a significant (p adj < 0.01) change in 48.8% (637 out of 1,305) of proteins detected by SOMAscan. Gene set enrichment showed that the most impacted biological processes involved myeloid cell activation. Specifically, activation and degranulation of neutrophils were the top five highest-scoring processes. Pathway analyses with the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that metabolic enzymes, particularly those of glycolysis, were elevated in serum concentration after surgery. Several proteins were significantly increased postoperatively in patients diagnosed with POD relative to the non-POD controls, with interleukin-6 (IL-6) showing the greatest fold-change. LPS stimulation of whole blood samples confirmed these findings. Linear regression analysis showed a highly significant correlation between Confusion Assessment Method (CAM) scores and CPB-mediated changes in cGMP-inhibited 3',5'-cyclic phosphodiesterase A (PDE3A).ConclusionsCardiac surgery with CPB resulted in inflammasome changes accompanied by unexpected increases in metabolic pathways. In exploratory analyses, we found that POD was associated with changes in the expression level of various proteins, most notably IL-6 and PDE3A. This study and ongoing protein biomarker studies will likely help quantify risk or confirm the diagnosis for POD and increase understanding of its pathophysiological mechanisms.
| S-EPMC8386117 | biostudies-literature
Project description:Iron metabolism disorder has been identified as a contributor to the pathogenesis and progression of multiple cognitive dysfunction-related diseases, including postoperative delirium. However, the association between preoperative iron reserves and postoperative delirium risk remains elusive. This retrospective cohort study aimed to explore the impact of preoperative serum ferritin levels on the risk of postoperative delirium in elderly patients undergoing non-neurosurgical and non-cardiac procedures. Conducted at the Chinese PLA General Hospital between January 2014 and December 2021, the study finally included 12,841 patients aged 65 years and above. Preoperative serum ferritin levels were assessed within 30 days before surgery, and postoperative delirium occurrence within the first seven days after surgery was determined through medical chart review. The analyses revealed that both low and high levels of serum ferritin were associated with an increased risk of postoperative delirium. Patients in the lowest quintile of serum ferritin exhibited an 81% increased risk, while those in the highest quintile faced a 91% increased risk compared to those in the second quintile. Furthermore, mediation analyses indicated that the direct effect of preoperative serum ferritin on postoperative delirium contradicted its indirect effect mediated by hemoglobin levels. These findings suggest that maintaining serum ferritin within moderate range preoperatively could be beneficial for managing postoperative delirium risk among elderly patients.
| S-EPMC11405726 | biostudies-literature
Project description: Not available
| S-EPMC8453356 | biostudies-literature
Project description:PurposeAcute postoperative hypertension (APH) is a common complication during the anesthesia recovery period that can lead to adverse outcomes, including cardiovascular and cerebrovascular accidents. Identification of risk factors for APH will allow for preoperative optimization and appropriate perioperative management. This study aimed to identify risk factors for APH.Patients and methodsIn this retrospective single-center study, 1,178 cases were included. Data was entered by two investigators, and consistency analysis was performed by another. Patients were divided into APH and non-APH groups. A predictive model was built by multivariate stepwise logistic regression. The predictive ability of the logistic regression model was tested by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Hosmer and Lemeshow goodness-of-fit (GOF) test was performed to reflect the goodness of fit of the model. Calibration curve was created to represent the relationship between predicted risk and observed frequency. Sensitivity analysis was performed to evaluate the robustness of the results.ResultsMultivariate logistic regression analysis showed that age over 65 years (OR = 3.07, 95% CI: 2.14 ~ 4.42, P < 0.001), female patients (OR = 1.37, 95% CI: 1.02 ~ 1.84, P = 0.034), presence of intraoperative hypertension (OR = 2.15, 95% CI: 1.57 ~ 2.95, P < 0.001), and use of propofol in PACU (OR = 2.14, 95% CI: 1.49 ~ 3.06, P < 0.001) were risk factors for APH. Intraoperative use of dexmedetomidine (OR = 0.66, 95% CI: 0.49 ~ 0.89, P = 0.007) was a protective factor. Higher baseline SBP (OR = 0.90, 95% CI: 0.89 ~ 0.92, P < 0.001) also showed some correlation with APH.ConclusionsThe risk of acute postoperative hypertension increased with age over 65 years, female patients, intraoperative hypertension and restlessness during anesthesia recovery. Intraoperative use of dexmedetomidine was a protective factor for APH.
| S-EPMC10186778 | biostudies-literature
Project description:Postoperative delirium is common in patients recovering from cardiac surgery. Tight glucose control has been shown to reduce mortality and morbidity. Therefore, the authors sought to determine the effect of tight intraoperative glucose control using a hyperinsulinemic-normoglycemic clamp approach on postoperative delirium in patients undergoing cardiac surgery.The authors enrolled 198 adult patients having cardiac surgery in this randomized, double-blind, single-center trial. Patients were randomly assigned to either tight intraoperative glucose control with a hyperinsulinemic-normoglycemic clamp (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin administration with blood glucose target, <150 mg/dl). Delirium was assessed using a comprehensive delirium battery. The authors considered patients to have experienced postoperative delirium when Confusion Assessment Method testing was positive at any assessment. A positive Confusion Assessment Method was defined by the presence of features 1 (acute onset and fluctuating course) and 2 (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness).Patients randomized to tight glucose control were more likely to be diagnosed as being delirious than those assigned to routine glucose control (26 of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after adjusting for preoperative usage of calcium channel blocker and American Society of Anesthesiologist physical status. Delirium severity, among patients with delirium, was comparable with each glucose management strategy.Intraoperative hyperinsulinemic-normoglycemia augments the risk of delirium after cardiac surgery, but not its severity.
| S-EPMC4440226 | biostudies-literature
Project description:BackgroundDelirium 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.MethodsThe 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.ResultsC-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).ConclusionsElevated 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.
| S-EPMC5035711 | biostudies-literature
Project description: Not available
| S-EPMC11837761 | biostudies-literature
Project description:IntroductionAcute kidney injury (AKI) after cardiac surgery is independently associated with a prolonged hospital stay, increased cost of care, and increased post-operative mortality. Delayed elevation of serum creatinine (SCr) levels requires novel biomarkers to provide a prediction of AKI after cardiac surgery. Our objective was to find a novel blood biomarkers combination to construct a model for predicting AKI after cardiac surgery and risk stratification.MethodsThis was a case-control study. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to Gene Expression Omnibus (GEO) dataset GSE30718 to seek potential biomarkers associated with AKI. We measured biomarker levels in venous blood samples of 67 patients with AKI after cardiac surgery and 59 control patients in two cohorts. Clinical data were collected. We developed a multi-biomarker model for predicting cardiac-surgery-associated AKI and compared it with a traditional clinical-factor-based model.ResultsFrom bioinformatics analysis and previous articles, we found 6 potential plasma biomarkers for the prediction of AKI. Among them, 3 biomarkers, such as growth differentiation factor 15 (GDF15), soluble suppression of tumorigenicity 2 (ST2, IL1RL1), and soluble urokinase plasminogen activator receptor (uPAR) were found to have prediction ability for AKI (area under the curve [AUC] > 0.6) in patients undergoing cardiac surgery. They were then incorporated into a multi-biomarker model for predicting AKI (C-statistic: 0.84, Brier 0.15) which outperformed the traditional clinical-factor-based model (C-statistic: 0.73, Brier 0.16).ConclusionOur research validated a promising plasma multi-biomarker model for predicting AKI after cardiac surgery.
| S-EPMC8795513 | biostudies-literature