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Objective: Numerous investigators have theorized that postoperative changes in Alzheimer's disease neuropathology may underlie postoperative neurocognitive disorders. Thus, we determined the relationship between postoperative changes in cognition and cerebrospinal (CSF) tau, p‐tau‐181p, or Aβ levels after non‐cardiac, non‐neurologic surgery in older adults. Methods: Participants underwent cognitive testing before and 6 weeks after surgery, and lumbar punctures before, 24 h after, and 6 weeks after surgery. Cognitive scores were combined via factor analysis into an overall cognitive index. In total, 110 patients returned for 6‐week postoperative testing and were included in the analysis. Results: There was no significant change from before to 24 h or 6 weeks following surgery in CSF tau (median [median absolute deviation] change before to 24 h: 0.00 [4.36] pg/mL, p = 0.853; change before to 6 weeks: −1.21 [3.98] pg/mL, p = 0.827). There were also no significant changes in CSF p‐tau‐181p or Aβ over this period. There was no change in cognitive index (mean [95% CI] 0.040 [−0.018, 0.098], p = 0.175) from before to 6 weeks after surgery, although there were postoperative declines in verbal memory (−0.346 [−0.523, −0.170], p = 0.003) and improvements in executive function (0.394, [0.310, 0.479], p < 0.001). There were no significant correlations between preoperative to 6‐week postoperative changes in cognition and CSF tau, p‐tau‐181p, or Aβ42 changes over this interval (p > 0.05 for each). Interpretation: Neurocognitive changes after non‐cardiac, non‐neurologic surgery in the majority of cognitively healthy, community‐dwelling older adults are unlikely to be related to postoperative changes in AD neuropathology (as assessed by CSF Aβ, tau or p‐tau‐181p levels or the p‐tau‐181p/Aβ or tau/Aβ ratios). Trial Registration: clinicaltrials.gov (NCT01993836). [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD), a syndrome of cognitive deficits occurring 1-12 months after surgery primarily in older patients, is associated with poor postoperative outcomes. POCD is hypothesized to result from neuroinflammation; however, the pathways involved remain unclear. Unbiased proteomic analyses have been used to identify neuroinflammatory pathways in multiple neurologic diseases and syndromes but have not yet been applied to POCD.Objective: To utilize unbiased mass spectrometry-based proteomics to identify potential neuroinflammatory pathways underlying POCD.Methods: Unbiased LC-MS/MS proteomics was performed on immunodepleted cerebrospinal fluid (CSF) samples obtained before, 24 hours after, and 6 weeks after major non-cardiac surgery in older adults who did (n = 8) or did not develop POCD (n = 6). Linear mixed models were used to select peptides and proteins with intensity differences for pathway analysis.Results: Mass spectrometry quantified 8,258 peptides from 1,222 proteins in > 50%of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between patients with versus withoutPOCD (q < 0.05), including proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these groups. Among these, pathway analysis revealed that 50 were from 17 proteins mapping to complement and coagulation pathways (q = 2.44*10-13).Conclusion: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD. [ABSTRACT FROM AUTHOR]

Background: Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened long-term postoperative cognitive trajectory is the Alzheimer's disease (AD) genetic risk factor APOE4. APOE4 is thought to elevate AD risk partly by increasing neuroinflammation, which is also a theorized mechanism for PND. Yet, it is unclear whether modulating apoE4 protein signaling in older surgical patients would reduce PND risk or severity.Objective: MARBLE is a randomized, blinded, placebo-controlled phase II sequential dose escalation trial designed to evaluate perioperative administration of an apoE mimetic peptide drug, CN-105, in older adults (age≥60 years). The primary aim is evaluating the safety of CN-105 administration, as measured by adverse event rates in CN-105 versus placebo-treated patients. Secondary aims include assessing perioperative CN-105 administration feasibility and its efficacy for reducing postoperative neuroinflammation and PND severity.Methods: 201 patients undergoing non-cardiac, non-neurological surgery will be randomized to control or CN-105 treatment groups and receive placebo or drug before and every six hours after surgery, for up to three days after surgery. Chart reviews, pre- and postoperative cognitive testing, delirium screening, and blood and CSF analyses will be performed to examine effects of CN-105 on perioperative adverse event rates, cognition, and neuroinflammation. Trial results will be disseminated by presentations at conferences and peer-reviewed publications.Conclusion: MARBLE is a transdisciplinary study designed to measure CN-105 safety and efficacy for preventing PND in older adults and to provide insight into the pathogenesis of these geriatric syndromes. [ABSTRACT FROM AUTHOR]

OVERVIEW As interventionalists, there is a constant need to perform a variety of procedures ranging from the minimally-invasive to more complex open surgeries. For many of these procedures, there is a role for a number of local and regional anesthetics, several of which can be completed without the assistance of an anesthesiologist. This article is the first in a series that discusses the role that anesthesia plays in the modern practice of interventional medicine. [ABSTRACT FROM AUTHOR]

Objectives: Electronic health information overload makes it difficult for providers to quickly find and interpret information to support care decisions. The purpose of this study was to better understand how clinicians use information in critical care to support the design of improved presentation of electronic health information., Methods: We conducted a contextual analysis and visioning project. We used an eye-tracker to record 20 clinicians' information use activities in critical care settings. We played video recordings back to clinicians in retrospective cued interviews and queried: 1) context and goals of information use, 2) impacts of current display design on use, and 3) processes related to information use. We analyzed interview transcripts using grounded theory-based content analysis techniques and identified emerging themes. From these, we conducted a visioning activity with a team of subject matter experts and identified key areas for focus of design and research for future display designs., Results: Analyses revealed four unique critical care information use activities including new patient assessment, known patient status review, specific directed information seeking, and review and prioritization of multiple patients. Emerging themes were primarily related to a need for better representation of dynamic data such as vital signs and laboratory results, usability issues associated with reducing cognitive load and supporting efficient interaction, and processes for managing information. Visions for the future included designs that: 1) provide rapid access to new information, 2) organize by systems or problems as well as by current versus historical patient data, and 3) apply intelligence toward detecting and representing change and urgency., Conclusions: The results from this study can be used to guide the design of future acute care electronic health information display. Additional research and collaboration is needed to refine and implement intelligent graphical user interfaces to improve clinical information organization and prioritization to support care decisions.