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OBJECTIVE: This study aims to identify blood biomarkers of postoperative delirium. BACKGROUND: Phosphorylated tau at threonine 217 (Tau-PT217) and 181 (Tau-PT181) are new Alzheimer disease biomarkers. Postoperative delirium is associated with Alzheimer disease. We assessed associations between Tau-PT217 or Tau-PT181 and postoperative delirium. METHODS: Of 491 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy, 139 participants were eligible and included in the analysis. Presence and severity of postoperative delirium were assessed in the patients. Preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were determined by a newly established Nanoneedle technology. RESULTS: Of 139 participants (73±6 years old, 55% female), 18 (13%) developed postoperative delirium. Participants who developed postoperative delirium had higher preoperative plasma concentrations of Tau-PT217 and Tau-PT181 than participants who did not. Preoperative plasma concentrations of Tau-PT217 or Tau-PT181 were independently associated with postoperative delirium after adjusting for age, education, and preoperative Mini-Mental State score [odds ratio (OR) per unit change in the biomarker: 2.05, 95% confidence interval (CI):1.61-2.62, P

ObjectivesTo describe sedative and analgesic drug utilization in a cohort of critically ill patients with coronavirus disease 2019 and compare standard sedation with an alternative approach using inhaled isoflurane.DesignThis was a retrospective cohort study designed to compare doses of sedatives between ICU patients receiving standard IV sedation and patients receiving mixed sedation including inhaled isoflurane. Data were obtained from electronic medical records.SettingICU at large academic medical center where mechanical ventilation was delivered with Draeger Apollo (Draeger Medical, Telford, PA) anesthesia machines.PatientsConsecutive adult patients (≥ 18 yr) with confirmed coronavirus disease 2019 admitted to ICU between April 2, 2020, and May 4, 2020.InterventionsNone.Measurements and main resultsThirty-five mechanically ventilated patients were included in the study, with a mean (sd) age of 59.4 (12.8) years. Twenty-three patients (65.7%) were men. Seventeen patients (48.6%) received standard IV sedation, whereas 18 (51.4%) also received isoflurane. The mean duration of mechanical ventilation (sd) was 23.3 (11.6) days in the standard sedation group and 23.8 (12.5) days in the isoflurane group. Mean (sd) duration of isoflurane exposure was 5.61 (2.99) days, representing 29.1% of total sedation time (sd, 20.4). Cumulative opioid exposure did not differ between the standard sedation and isoflurane sedation groups (mean morphine milligram equivalent 6668 [sd, 1,346] vs 6678 [sd, 2,000] mg). However, the initiation of isoflurane in patients was associated with decreased utilization of propofol (mean daily amount 3,656 [sd, 1,635] before vs 950 [sd, 1,804] mg during isoflurane) and hydromorphone (mean daily amount 48 [sd, 30] before vs 23 [sd, 27] mg).ConclusionsIn the subjects that received isoflurane, its use was associated with significant decreases in propofol and hydromorphone infusions.

The purpose of this article is to provide a succinct summary of the different experimental approaches that have been used in preclinical postoperative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how the many different approaches have contributed to our understanding of postoperative cognitive dysfunction, and to identify knowledge gaps to be filled by further research. The authors have organized this report by the level of experimental and systems complexity, starting with molecular and cellular approaches, then moving to intact invertebrates and vertebrate animal models. In addition, the authors goal is to improve the quality and consistency of postoperative cognitive dysfunction and perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and best practices in experimental design and reporting to increase the likelihood of corroborating results. Thus, the authors conclude with general guidelines for designing, conducting and reporting perioperative neurocognitive disorder rodent research.

The purpose of this article is to provide a succinct summary of the different experimental approaches that have been used in preclinical postoperative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how the many different approaches have contributed to our understanding of postoperative cognitive dysfunction, and to identify knowledge gaps to be filled by further research. The authors have organized this report by the level of experimental and systems complexity, starting with molecular and cellular approaches, then moving to intact invertebrates and vertebrate animal models. In addition, the authors' goal is to improve the quality and consistency of postoperative cognitive dysfunction and perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and "best practices" in experimental design and reporting to increase the likelihood of corroborating results. Thus, the authors conclude with general guidelines for designing, conducting and reporting perioperative neurocognitive disorder rodent research.

Background: Spouses of Alzheimer's disease (AD) patients are at a higher risk of developing incidental dementia. However, the causes and underlying mechanism of this clinical observation remain largely unknown. One possible explanation is linked to microbiota dysbiosis, a condition that has been associated with AD. However, it remains unclear whether gut microbiota dysbiosis can be transmitted from AD individuals to non‐AD individuals and contribute to the development of AD pathogenesis and cognitive impairment. Method: We, therefore, set out to perform both animal studies and clinical investigation by co‐housing wild‐type mice and AD transgenic mice, analyzing microbiota via 16S rRNA gene sequencing, measuring short‐chain fatty acid amounts, and employing behavioral test, mass spectrometry, site‐mutations and other methods. Result: The present study revealed that co‐housing between wildtype mice and AD transgenic mice or administrating feces of AD transgenic mice to wild‐type mice resulted in AD‐associated gut microbiota dysbiosis, Tau phosphorylation, and cognitive impairment in the wild‐type mice. Gavage with Lactobacillus and Bifidobacterium restored these changes in the wild‐type mice. The oral and gut microbiota of AD patient partners resembled that of AD patients but differed from healthy controls, indicating the transmission of microbiota. The underlying mechanism of these findings includes that the butyric acid‐mediated acetylation of GSK3β at lysine 15 regulated its phosphorylation at serine 9, consequently impacting Tau phosphorylation. Conclusion: This initial proof‐of‐concept study demonstrated the potential transmission of microbiota from AD patients or ADTg mice to non‐AD controls or WT mice housed together. This transmission may contribute to the development of AD‐associated microbiota dysbiosis and metabolite alterations, ultimately leading to AD pathogenesis and cognitive impairment. However, these findings should be validated in future studies. The results of this study are expected to drive further research to explore gut microbiota dysbiosis and its connection to AD in both preclinical and clinical contexts. [ABSTRACT FROM AUTHOR]

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Background: Surgery may be associated with postoperative cognitive impairment in elder participants, yet the extent of its association with mild cognitive impairment (MCI) remains undetermined. Objective: To determine the relationship between surgery and MCI. Methods: The data of participants from the Alzheimer's Disease Neuroimaging Initiative were analyzed, including individuals with MCI or normal cognition. We focused on surgeries conducted after the age of 45, categorized by the number of surgeries, surgical risk, and the age at which surgeries occurred. Multivariable logistic regression was employed to determine the association between surgery and the development of MCI. Results: The study is comprised of 387 individuals with MCI and 578 cognitively normal individuals. The overall surgery exposure (adjusted OR = 1.14, [95% CI 0.83, 1.56], p = 0.43) and the number of surgeries (adjusted OR = 0.92 [0.62, 1.36], p = 0.67 for single exposure, adjusted OR = 1.12 [0.71, 1.78], p = 0.63 for two exposures, adjusted OR = 1.38 [0.95, 2.01], p = 0.09 for three or more exposures compared to no exposure as the reference) were not associated with the development of MCI. However, high-risk surgeries (adjusted OR = 1.79 [1.00, 3.21], p = 0.049) or surgeries occurring after the age of 75 (adjusted OR = 2.01 [1.03, 3.90], p = 0.041) were associated with a greater risk of developing MCI. Conclusions: High risk surgeries occurring at an older age contribute to the development of MCI, indicating a complex of mechanistic insights for the development of postoperative cognitive impairment. [ABSTRACT FROM AUTHOR]

Preoperative risk biomarkers for delirium may aid in identifying high-risk patients and developing intervention therapies, which would minimize the health and economic burden of postoperative delirium. Previous studies have typically used single omics approaches to identify such biomarkers. Preoperative cerebrospinal fluid (CSF) from the Healthier Postoperative Recovery study of adults ≥ 63 years old undergoing elective major orthopedic surgery was used in a matched pair delirium case–no delirium control design. We performed metabolomics and lipidomics, which were combined with our previously reported proteomics results on the same samples. Differential expression, clustering, classification, and systems biology analyses were applied to individual and combined omics datasets. Probabilistic graph models were used to identify an integrated multi-omics interaction network, which included clusters of heterogeneous omics interactions among lipids, metabolites, and proteins. The combined multi-omics signature of 25 molecules attained an AUC of 0.96 [95% CI: 0.85–1.00], showing improvement over individual omics-based classification. We conclude that multi-omics integration of preoperative CSF identifies potential risk markers for delirium and generates new insights into the complex pathways associated with delirium. With future validation, this hypotheses-generating study may serve to build robust biomarkers for delirium and improve our understanding of its pathophysiology. [ABSTRACT FROM AUTHOR]

The quality and standardized training and certification of young physicians is key to the quality of health care in the future. In contrast to the American system, there is no nationwide and standardized oral examination in the training and certification process for anesthesiologists in China. The adoptability of the American anesthesia oral examination in China, as well as potential roadblocks, has not been specifically discussed. In this commentary, we share our experience of introducing the American oral examination to an audience of Chinese anesthesiologists and propose a pragmatic approach for adopting the anesthesia oral examination in China. This initiative has the potential to reform the current anesthesia training and certification process and improve the quality of anesthetic care in China.

BackgroundScholarly activity is expected of program directors of Accreditation Council for Graduate Medical Education (ACGME)-accredited residency training programs. Anesthesiology residency programs are cited more often than surgical programs for deficiencies in academic productivity. We hypothesized that this may in part reflect differences in scholarly activity between program directors of anesthesiology and surgical trainings programs. To test the hypothesis, we examined the career track record of current program directors of ACGME-accredited anesthesiology and surgical residency programs at the same institutions using PubMed citations and funding from the National Institutes of Health (NIH) as metrics of scholarly activity.MethodsBetween November 1, 2011 and December 31, 2011, we obtained data from publicly available Web sites on program directors at 127 institutions that had ACGME-accredited programs in both anesthesiology and surgery. Information gathered on each individual included year of board certification, year first appointed program director, academic rank, history of NIH grant funding, and number of PubMed citations. We also calculated the h-index for a randomly selected subset of 25 institution-matched program directors.ResultsThere were no differences between the groups in number of years since board certification (P = 0.42), academic rank (P = 0.38), or years as a program director (P = 0.22). However, program directors in anesthesiology had less prior or current NIH funding (P = 0.002), fewer total and education-related PubMed citations (both P < 0.001), and a lower h-index (P = 0.001) than surgery program directors. Multivariate analysis revealed that the publication rate for anesthesiology program directors was 43% (95% confidence interval, 0.31-0.58) that of the corresponding program directors of surgical residency programs, holding other variables constant.ConclusionsProgram directors of anesthesiology residency programs have considerably less scholarly activity in terms of peer-reviewed publications and federal research funding than directors of surgical residency programs. As such, this study provides further evidence for a systemic weakness in the scholarly fabric of academic anesthesiology.