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  • 1
    Online Resource
    Online Resource
    Patterns and Persistence of Perioperative Plasma and Cerebrospinal Fluid Neuroinflammatory Protein Biomarkers After Elective Orthopedic Surgery Using SOMAscan
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Anesthesia & Analgesia Vol. 136, No. 1 ( 2023-01), p. 163-175
    Details
    In: Anesthesia & Analgesia, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. 1 ( 2023-01), p. 163-175
    Abstract: The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF. We hypothesized that biological pathways identified by these proteins would be in the categories of neuroinflammation and neuronal function and define neuroinflammatory proteome changes associated with surgery in older patients. METHODS: SOMAscan analyzed 1305 proteins in blood plasma (n = 14) and CSF (n = 15) samples from older patients enrolled in the Role of Inflammation after Surgery for Elders (RISE) study undergoing elective hip and knee replacement surgery with spinal anesthesia. Systems biology analysis identified biological pathways enriched among the surgery-associated differentially expressed proteins in plasma and CSF. RESULTS: Comparison of postoperative day 1 (POD1) to preoperative (PREOP) plasma protein levels identified 343 proteins with postsurgical changes ( P 〈 .05; absolute value of the fold change [|FC|] 〉 1.2). Comparing postoperative 1-month (PO1MO) plasma and CSF with PREOP identified 67 proteins in plasma and 79 proteins in CSF with altered levels ( P 〈 .05; |FC| 〉 1.2). In plasma, 21 proteins, primarily linked to immune response and inflammation, were similarly changed at POD1 and PO1MO. Comparison of plasma to CSF at PO1MO identified 8 shared proteins. Comparison of plasma at POD1 to CSF at PO1MO identified a larger number, 15 proteins in common, most of which are regulated by interleukin-6 (IL-6) or transforming growth factor beta-1 (TGFB1) and linked to the inflammatory response. Of the 79 CSF PO1MO-specific proteins, many are involved in neuronal function and neuroinflammation. CONCLUSIONS: SOMAscan can characterize both short- and long-term surgery-induced protein alterations in plasma and CSF. Acute plasma protein changes at POD1 parallel changes in PO1MO CSF and suggest 15 potential biomarkers for longer-term neuroinflammation that warrant further investigation.
    Type of Medium: Online Resource
    ISSN: 0003-2999
    URL: Article
    DOI: 10.1213/ANE.0000000000005991
    RVK:
    XA 22250
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2018275-2
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  • 2
    Online Resource
    Online Resource
    Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Annals of Surgery Vol. 273, No. 4 ( 2021-04), p. 732-742
    Details
    In: Annals of Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 273, No. 4 ( 2021-04), p. 732-742
    Abstract: To characterize the proteomic signature of surgery in older adults and association with postoperative outcomes. Summary of Background Data: Circulating plasma proteins can reflect the physiological response to and clinical outcomes after surgery. Methods: Blood plasma from older adults undergoing elective surgery was analyzed for 1305 proteins using SOMAscan. Surgery-associated proteins underwent Ingenuity Pathways Analysis. Selected surgery-associated proteins were independently validated using Luminex or enzyme-linked immunosorbent assay methods. Generalized linear models estimated correlations with postoperative outcomes. Results: Plasma from a subcohort (n = 36) of the Successful Aging after Elective Surgery (SAGES) study was used for SOMAscan. Systems biology analysis of 110 proteins with Benjamini-Hochberg (BH) corrected P value ≤0.01 and an absolute foldchange (|FC|) ≥1.5 between postoperative day 2 (POD2) and preoperative (PREOP) identified functional pathways with major effects on pro-inflammatory proteins. Chitinase-3-like protein 1 (CHI3L1), C-reactive protein (CRP), and interleukin-6 (IL-6) were independently validated in separate validation cohorts from SAGES (n = 150 for CRP, IL-6; n = 126 for CHI3L1). Foldchange CHI3L1 and IL-6 were associated with increased postoperative complications [relative risk (RR) 1.50, 95% confidence interval (95% CI) 1.21–1.85 and RR 1.63, 95% CI 1.18–2.26, respectively], length of stay (RR 1.35, 95% CI 0.77–1.92 and RR 0.98, 95% CI 0.52–1.45), and risk of discharge to postacute facility (RR 1.15, 95% CI 1.04–1.26 and RR 1.11, 95% CI 1.04–1.18); POD2 and PREOP CRP difference was associated with discharge to postacute facility (RR 1.14, 95% CI 1.04–1.25). Conclusion: SOMAscan can identify novel and clinically relevant surgery-induced protein changes. Ultimately, proteomics may provide insights about pathways by which surgical stress contributes to postoperative outcomes.
    Type of Medium: Online Resource
    ISSN: 0003-4932 , 1528-1140
    URL: Article
    DOI: 10.1097/SLA.0000000000003283
    RVK:
    XA 23900
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2641023-0
    detail.hit.zdb_id: 2002200-1
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  • 3
    Online Resource
    Online Resource
    F5‐01‐04: INFLAMMATION AS A POTENTIAL SHARED MECHANISM FOR POSTOPERATIVE DELIRIUM AND LONG‐TERM COGNITIVE DECLINE IN OLDER ADULTS UNDERGOING MAJOR SURGERY
    Wiley ; 2019
    In:  Alzheimer's & Dementia Vol. 15, No. 7S_Part_31 ( 2019-07)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 15, No. 7S_Part_31 ( 2019-07)
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Article
    DOI: 10.1016/j.jalz.2019.06.4826
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2201940-6
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  • 4
    Online Resource
    Online Resource
    Aptamer-Based Proteomics Measuring Preoperative Cerebrospinal Fluid Protein Alterations Associated with Postoperative Delirium
    MDPI AG ; 2023
    In:  Biomolecules Vol. 13, No. 9 ( 2023-09-15), p. 1395-
    Details
    In: Biomolecules, MDPI AG, Vol. 13, No. 9 ( 2023-09-15), p. 1395-
    Abstract: Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to a 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 the 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, and 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 identified 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.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom13091395
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2701262-1
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  • 5
    Online Resource
    Online Resource
    Targeted metabolomics analysis of postoperative delirium
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-01-15)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-01-15)
    Abstract: Postoperative delirium is the most common complication among older adults undergoing major surgery. The pathophysiology of delirium is poorly understood, and no blood-based, predictive markers are available. We characterized the plasma metabolome of 52 delirium cases and 52 matched controls from the Successful Aging after Elective Surgery (SAGES) cohort (N = 560) of patients ≥ 70 years old without dementia undergoing scheduled major non-cardiac surgery. We applied targeted mass spectrometry with internal standards and pooled controls using a nested matched case-control study preoperatively (PREOP) and on postoperative day 2 (POD2) to identify potential delirium risk and disease markers. Univariate analyses identified 37 PREOP and 53 POD2 metabolites associated with delirium and multivariate analyses achieved significant separation between the two groups with an 11-metabolite prediction model at PREOP (AUC = 83.80%). Systems biology analysis using the metabolites with differential concentrations rendered “valine, leucine, and isoleucine biosynthesis” at PREOP and “citrate cycle” at POD2 as the most significantly enriched pathways (false discovery rate  〈  0.05). Perturbations in energy metabolism and amino acid synthesis pathways may be associated with postoperative delirium and suggest potential mechanisms for delirium pathogenesis. Our results could lead to the development of a metabolomic delirium predictor.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-020-80412-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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