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Potential Serum Biomarkers for Postoperative Neurocognitive Disorders Based on Proteomic Analysis of Cognitive-Related Brain Regions

ABSTRACT: Postoperative neurocognitive disorders (po-NCD), including postoperative delirium (POD) and delayed neurocognitive recovery (dNCR), are common in geriatric surgical patients. However, the ideal diagnostic biomarkers to predict individual risks of po-NCDs have not been identified. In this study, proteomic analysis was used to detect dysregulated proteins in three cognitive-related brain regions, the hippocampus, prefrontal cortex, and temporal lobe, of aged dNCR rats. The common affected proteins in these three brain regions were further verified by real-time polymerase chain reaction and western blotting. Furthermore, serum samples from aged rats with dNCR and elderly hip fracture patients with POD were also assessed with enzyme linked immunosorbent assays to investigate the biomarker potential of these dysregulated proteins. The increased expression levels of haptoglobin, caseinolytic protease (ClpP), and alpha-2 macroglobulin (A2M) as well as decreased expression levels of 14-3-3β/α and biliverdin reductase-A (BVR-A) were validated by proteomic analysis in the hippocampus, prefrontal cortex, and temporal lobe of aged dNCR rats. The increased expression of haptoglobin and decreased expression of 14-3-3β/α were further demonstrated in the three brain regions by western blotting. Moreover, increased levels of S100A6 and BVR-A in the hippocampus, S100A6 in the prefrontal cortex, and A2M in the temporal lobe were also observed. More intriguingly, both decreased serum 14-3-3β/α and increased A2M in geriatric POD patients as well as decreased serum ClpP in aged dNCR rats were verified. These results not only indicate potential diagnostic biomarkers for po-NCD but also provide directions for further pathological investigations. Clinical Trial Registration:www.ClinicalTrials.gov, identifier [ChiCTR1900027393].

SUBMITTER: Li Y

PROVIDER: S-EPMC8511679 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportancePostoperative neurocognitive disorders (PNDs) after surgical procedures are common and may be associated with increased health care expenditures.ObjectiveTo quantify the economic burden associated with a PND diagnosis in 1 year following surgical treatment among older patients in the United States.Design, setting, and participantsThis retrospective cohort study used claims data from the Bundled Payments for Care Improvement Advanced Model from 4285 hospitals that submitted Medicare Fee-for-service (FFS) claims between January 2013 and December 2016. All Medicare patients aged 65 years or older who underwent an inpatient hospital admission associated with a surgical procedure, did not experience a PND before index admission, and were not undergoing dialysis or concurrently enrolled in Medicaid were included. Data were analyzed from October 2019 and May 2020.ExposuresPND, defined as an International Classification of Diseases, Ninth or Tenth Revision, diagnosis of delirium, mild cognitive impairment, or dementia within 1 year of discharge from the index surgical admission.Main outcomes and measuresThe primary outcome was total inflation-adjusted Medicare postacute care payments within 1 year after the index surgical procedure.ResultsA total of 2 380 473 patients (mean [SD] age, 75.36 (7.31) years; 1 336 736 [56.1%] women) who underwent surgical procedures were included, of whom 44 974 patients (1.9%) were diagnosed with a PND. Among all patients, most were White (2 142 157 patients [90.0%]), presenting for orthopedic surgery (1 523 782 patients [64.0%]) in urban medical centers (2 179 893 patients [91.6%]) that were private nonprofits (1 798 749 patients [75.6%]). Patients with a PND, compared with those without a PND, experienced a significantly longer hospital length of stay (mean [SD], 5.91 [6.01] days vs 4.29 [4.18] days; P < .001), were less likely to be discharged home (9947 patients [22.1%] vs 914 925 patients [39.2%]; P < .001), and had a higher incidence of mortality at 1 year after treatment (4580 patients [10.2%] vs 103 767 patients [4.4%]; P < .001). After adjusting for patient and hospital characteristics, the presence of a PND within 1 year of the index procedure was associated with an increase of $17 275 (95% CI, $17 058-$17 491) in cost in the 1-year postadmission period (P < .001).Conclusions and relevanceThe findings of this cohort study suggest that among older Medicare patients undergoing surgical treatment, a diagnosis of a PND was associated with an increase in health care costs for up to 1 year following the surgical procedure. Given the magnitude of this cost burden, PNDs represent an appealing target for risk mitigation and improvement in value-based health care.

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Potential Serum Biomarkers for Postoperative Neurocognitive Disorders Based on Proteomic Analysis of Cognitive-Related Brain Regions

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