scholarly journals Targeted metabolomics analysis of postoperative delirium

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bridget A. Tripp ◽  
Simon T. Dillon ◽  
Min Yuan ◽  
John M. Asara ◽  
Sarinnapha M. Vasunilashorn ◽  
...  
Keyword(s):  
Successful Aging ◽  
Postoperative Delirium ◽  
Elective Surgery ◽  
Acid Synthesis ◽  
Major Surgery ◽  
Amino Acid Synthesis ◽  
Citrate Cycle ◽  
Plasma Metabolome ◽  
Matched Case ◽  
Univariate Analyses

AbstractPostoperative 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.

scholarly journals AN INFLAMMATORY SIGNATURE OF POSTOPERATIVE DELIRIUM

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S820-S821
Author(s):  
Sarinnapha Vasunilashorn ◽  
Long H Ngo ◽  
Simon Dillon ◽  
Hasan Otu ◽  
Bridget Tripp ◽  
...  
Keyword(s):  
Successful Aging ◽  
Inflammatory Markers ◽  
Postoperative Delirium ◽  
Linear Models ◽  
Elective Surgery ◽  
Geriatric Syndrome ◽  
Reactive Protein ◽  
Increased Risk ◽  
Comorbidity Index ◽  
Inflammatory Proteins

Abstract Delirium is a common, morbid, and costly geriatric syndrome, yet its pathophysiology remains poorly understood. In a nested matched case-control study within the Successful Aging after Elective Surgery (SAGES) study, a cohort of adults age ≥70 without dementia undergoing major non-cardiac surgery, we previously identified inflammatory proteins to be associated with delirium. Using the entire SAGES cohort, the current study examines the independent associations of these inflammatory proteins with postoperative delirium. Plasma was collected preoperatively (PREOP) and on postoperative day 2 (POD2). Neuroinflammatory marker chitinase-3-like protein [CHI3l1 or YKL-40]; PREOP and POD2) and systemic inflammatory markers interleukin [IL]-6 (POD2 only) and C-reactive protein (CRP; PREOP and POD2) were measured using enzyme-linked immunosorbent assays. Generalized linear models were used to determine the independent (multivariable) associations between the inflammatory markers, measured in sample-based quartiles (Q). All models adjusted for age, sex, baseline cognition, surgery type, Charlson comorbidity index, and medical complications. Among the 555 patients (mean age 77 years, standard deviation, SD 5.2), 58% were female and 86% underwent orthopedic surgeries. Postoperative delirium occurred in 24%. High YKL-40 PREOP and IL-6 at POD2 (Q4 vs. Q1) were significantly associated with an increased risk of delirium: relative risk (RR) [95% confidence interval (CI)] 2.2[1.1-4.4] and 2.7[1.3-5.7], respectively. CRP (PREOP and POD2) was not significantly associated with delirium (p=0.37 and p=0.73, respectively). This work underscores the importance of inflammation (YKL-40 and IL-6) in the pathophysiology of postoperative delirium.

scholarly journals Functional brain network and trail making test changes after major surgery and delirium

2021 ◽  
Author(s):  
Simone JT van Montfort ◽  
Fienke L Ditzel ◽  
Ilse MJ Kant ◽  
Ellen Aarts ◽  
Lisette M Vernooij ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Postoperative Delirium ◽  
Elective Surgery ◽  
Brain Network ◽  
Major Surgery ◽  
Functional Brain ◽  
Functional Brain Network ◽  
Trail Making ◽  
Functional Connectivity Strength ◽  
Connectivity Strength

AbstractBackgroundDelirium is a frequent complication of elective surgery in elderly patients, associated with an increased risk of long-term cognitive impairment and dementia. Disturbances in the functional brain network were previously reported during delirium. We hypothesized persisting alterations in functional brain networks three months after elective surgery in patients with postoperative delirium, and hypothesized that postoperative brain connectivity changes (irrespective of delirium) are related to cognitive decline.MethodsElderly patients (N=554) undergoing elective surgery underwent clinical assessments (including Trail Making Test B (TMT-B) and resting-state functional magnetic resonance imaging (rs-fMRI) before and three months after surgery. Delirium was assessed on the first seven postoperative days. After strict motion correction, rs-fMRI connectivity strength and network characteristics were calculated in 246 patients (130 patients underwent scans at both timepoints), of whom 38 (16%) developed postoperative delirium.ResultsRs-fMRI functional connectivity strength increased after surgery in the total study population (β=0.006, 95%CI=0.000–0.012, p=0.021), but decreased after postoperative delirium (β=-0.014, 95%CI=0.000–0.012, p=0.026). No difference in TMT-B scores was found at follow-up between patients with and without postoperative delirium. Patients who decreased in functional connectivity strength declined in TMT-B scores compared to the group that did not (β=11.04, 95%CI=0.85-21.2, p=0.034).ConclusionsDelirium was associated with decreased functional connectivity strength three months after the syndrome was clinically resolved, which implies that delirium has lasting impact on brain networks. Decreased connectivity strength was associated with statistically significant (but not necessarily clinically relevant) cognitive deterioration after major surgery, which was not specifically related to delirium.Summary statementDelirium was associated with decreased resting-state fMRI functional connectivity strength three months after the syndrome was clinically resolved. Irrespective of delirium, decreased connectivity strength after major surgery was associated with a statistically significant cognitive deterioration.

scholarly journals Proteome-Wide Analysis Using SOMAscan Identifies and Validates Chitinase-3-Like Protein 1 as a Risk and Disease Marker of Delirium Among Older Adults Undergoing Major Elective Surgery

2021 ◽  
Author(s):  
Sarinnapha M Vasunilashorn ◽  
Simon T Dillon ◽  
Noel Y Chan ◽  
Tamara G Fong ◽  
Marie Joseph ◽  
...  
Keyword(s):  
Older Adults ◽  
Successful Aging ◽  
Postoperative Delirium ◽  
Linear Models ◽  
Elective Surgery ◽  
Protein Modeling ◽  
Full Cohort ◽  
Validation Data ◽  
Age Related

Abstract Background Delirium (an acute change in cognition) is a common, morbid, and costly syndrome seen primarily in aging adults. Despite increasing knowledge of its epidemiology, delirium remains a clinical diagnosis with no established biomarkers to guide diagnosis or management. Advances in proteomics now provide opportunities to identify novel markers of risk and disease progression for postoperative delirium and its associated long-term consequences (eg, long-term cognitive decline and Alzheimer’s disease [AD]). Methods In a nested matched case–control study (18 delirium/no-delirium pairs) within the Successful Aging after Elective Surgery study (N = 556), we evaluated the association of 1305 plasma proteins preoperatively [PREOP] and on postoperative day 2 [POD2]) with delirium using SOMAscan. Generalized linear models were applied to enzyme-linked immunosorbant assay (ELISA) validation data of one protein across the full cohort. Multi-protein modeling included delirium biomarkers identified in prior work (C-reactive protein, interleukin-6 [IL6]). Results We identified chitinase-3-like-protein-1 (CHI3L1/YKL-40) as the sole delirium-associated protein in both a PREOP and a POD2 predictor model, a finding confirmed by ELISA. Multi-protein modeling found high PREOP CHI3L1/YKL-40 and POD2 IL6 increased the risk of delirium (relative risk [95% confidence interval] Quartile [Q]4 vs Q1: 2.4[1.2–5.0] and 2.1[1.1–4.1], respectively). Conclusions Our identification of CHI3L1/YKL-40 in postoperative delirium parallels reports of CHI3L1/YKL-40 and its association with aging, mortality, and age-related conditions including AD onset and progression. This highlights the type 2 innate immune response, involving CHI3L1/YKL-40, as an underlying mechanism of postoperative delirium, a common, morbid, and costly syndrome that threatens the independence of older adults.

scholarly journals Postoperative Delirium and Postoperative Cognitive Dysfunction

2019 ◽  
Vol 131 (3) ◽  
pp. 477-491 ◽  
Author(s):  
Lori A. Daiello ◽  
Annie M. Racine ◽  
Ray Yun Gou ◽  
Edward R. Marcantonio ◽  
Zhongcong Xie ◽  
...  
Keyword(s):  
Relative Risk ◽  
Cognitive Dysfunction ◽  
Successful Aging ◽  
Postoperative Delirium ◽  
Elective Surgery ◽  
Postoperative Cognitive Dysfunction ◽  
Significant Risk ◽  
International Study ◽  
Neurocognitive Deficits

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up. Methods This study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method–based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months. Results One hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07–1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72–1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71–2.09). Conclusions Delirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

scholarly journals Longitudinal diffusion changes following postoperative delirium in older people without dementia

Neurology ◽  
2017 ◽  
Vol 89 (10) ◽  
pp. 1020-1027 ◽  
Author(s):  
Michele Cavallari ◽  
Weiying Dai ◽  
Charles R.G. Guttmann ◽  
Dominik S. Meier ◽  
Long H. Ngo ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Cognitive Performance ◽  
Sex Education ◽  
Successful Aging ◽  
Postoperative Delirium ◽  
Diffusion Tensor ◽  
Elective Surgery ◽  
Study Cohort ◽  
Longitudinal Diffusion ◽  
Cognitive Changes

Objective:To investigate the effect of postoperative delirium on longitudinal brain microstructural changes, as measured by diffusion tensor imaging.Methods:We studied a subset of the larger Successful Aging after Elective Surgery (SAGES) study cohort of older adults (≥70 years) without dementia undergoing elective surgery: 113 participants who had diffusion tensor imaging before and 1 year after surgery. Postoperative delirium severity and occurrence were assessed during the hospital stay using the Confusion Assessment Method and a validated chart review method. We investigated the association of delirium severity and occurrence with longitudinal diffusion changes across 1 year, adjusting for age, sex, vascular comorbidity, and baseline cognitive performance. We also assessed the association between changes in diffusion and cognitive performance across the 1-year follow-up period, adjusting for age, sex, education, and baseline cognitive performance.Results:Postoperative delirium occurred in 25 participants (22%). Delirium severity and occurrence were associated with longitudinal diffusion changes in the periventricular, frontal, and temporal white matter. Diffusion changes were also associated with changes in cognitive performance across 1 year, although the cognitive changes did not show significant association with delirium severity or occurrence.Conclusions:Our study raises the possibility that delirium has an effect on the development of brain microstructural abnormalities, which may reflect brain changes underlying cognitive trajectories. Future studies are warranted to clarify whether delirium is the driving factor of the observed changes or rather a correlate of a vulnerable brain that is at high risk for neurodegenerative processes.

Influence of increased nutrient supply on Microcystis aeruginosa at cellular and proteomic levels

2020 ◽  
Vol 85 ◽  
pp. 47-58
Author(s):  
Y Jiang ◽  
Y Liu
Keyword(s):  
Microcystis Aeruginosa ◽  
Regulatory Protein ◽  
Acid Synthesis ◽  
Nutrient Supply ◽  
Nitrogen Supply ◽  
Nitrogen And Phosphorus ◽  
Comprehensive Description ◽  
Amino Acid Synthesis ◽  
High Nutrient ◽  
Proteomic Responses

Various studies have observed that increased nutrient supply promotes the growth of bloom-forming cyanobacteria, but only a limited number of studies have investigated the influence of increased nutrient supply on bloom-forming cyanobacteria at the proteomic level. We investigated the cellular and proteomic responses of Microcystis aeruginosa to elevated nitrogen and phosphorus supply. Increased supply of both nutrients significantly promoted the growth of M. aeruginosa and the synthesis of chlorophyll a, protein, and microcystins. The release of microcystins and the synthesis of polysaccharides negatively correlated with the growth of M. aeruginosa under high nutrient levels. Overexpressed proteins related to photosynthesis, and amino acid synthesis, were responsible for the stimulatory effects of increased nutrient supply in M. aeruginosa. Increased nitrogen supply directly promoted cyanobacterial growth by inducing the overexpression of the cell division regulatory protein FtsZ. NtcA, that regulates gene transcription related to both nitrogen assimilation and microcystin synthesis, was overexpressed under the high nitrogen condition, which consequently induced overexpression of 2 microcystin synthetases (McyC and McyF) and promoted microcystin synthesis. Elevated nitrogen supply induced the overexpression of proteins involved in gas vesicle organization (GvpC and GvpW), which may increase the buoyancy of M. aeruginosa. Increased phosphorus level indirectly affected growth and the synthesis of cellular substances in M. aeruginosa through the mediation of differentially expressed proteins related to carbon and phosphorus metabolism. This study provides a comprehensive description of changes in the proteome of M. aeruginosa in response to an increased supply of 2 key nutrients.

O-AcylTEMPOs, a Modified and Fundamental, but Unexplored Carboxylic Derivative: Recent Progress in Synthetic Applications

2019 ◽  
Vol 23 (19) ◽  
pp. 2102-2121
Author(s):  
Hiroyuki Kawafuchi ◽  
Lijian Ma ◽  
Md Imran Hossain ◽  
Tsutomu Inokuchi
Keyword(s):  
Organic Synthesis ◽  
Recent Progress ◽  
Knoevenagel Condensation ◽  
Acid Synthesis ◽  
Amino Acid Synthesis ◽  
Electrophilic Amination ◽  
Weinreb Amides ◽  
Anionic Species ◽  
Diastereoselective Addition ◽  
Carbonyl Function

O-Acylated 2,2,6,6-tetramethylpiperidine-N-oxyls (abbr. O-AcylTEMPOs) are easily available and stable carboxylic derivatives, but their utility in organic synthesis is unexplored in contrast to analogues, such as the N-methoxy-N-methylamides, known as Weinreb amides. Especially, the O–N unit of the O-acylTEMPOs dictates a fairly electronwithdrawing character for the carbonyl function. This enhances the reactivity and stability of the resulting enolate ions. Accordingly, O-acylTEMPOs allow various transformations and this review encompasses seven topics: (1) Reactivity of O-acylTEMPOs towards nucleophiles and chemoselective transformations, (2) Reactivity of anionic species derived from O-acylTEMPOs, (3) E-Selective Knoevenagel condensation of acetoacetylTEMPOs and synthesis of furans, (4) Electrocyclization of 2,4-dienones derived from acetoacetic derivatives and 2-substituted enals, (5) Diastereoselective addition of amide anion to O-(2-alkenoyl)TEMPOs and &#946;-amino acid synthesis, (6) Thermolysis of O-acylTEMPOs, and (7) Applications for Umpolung reactions using O-benzoylTEMPOs, useful for the electrophilic amination of alkenes and alkynes.

scholarly journals Petasis vs. Strecker Amino Acid Synthesis: Convergence, Divergence and Opportunities in Organic Synthesis

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1707
Author(s):  
Wayiza Masamba
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Organic Synthesis ◽  
Acid Synthesis ◽  
Physical Sciences ◽  
Amino Acid Synthesis

α-Amino acids find widespread applications in various areas of life and physical sciences. Their syntheses are carried out by a multitude of protocols, of which Petasis and Strecker reactions have emerged as the most straightforward and most widely used. Both reactions are three-component reactions using the same starting materials, except the nucleophilic species. The differences and similarities between these two important reactions are highlighted in this review.

scholarly journals Enzymatic cascade systems for D-amino acid synthesis: progress and perspectives

2021 ◽  
Author(s):  
Anwen Fan ◽  
Jiarui Li ◽  
Yangqing Yu ◽  
Danping Zhang ◽  
Yao Nie ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Synthesis ◽  
Amino Acid Synthesis ◽  
Cascade Systems
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