Browsing by Author "Moretti, Eugene W"
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Item Open Access An Undiagnosed Paraganglioma in a 58-Year-Old Female Who Underwent Tumor Resection.(Case Rep Anesthesiol, 2017) Fox, William C; Read, Matthew; Moon, Richard E; Moretti, Eugene W; Colin, Brian JParagangliomas and pheochromocytomas are rare neuroendocrine tumors that can have high morbidity and mortality if undiagnosed. Here we report a case of an undiagnosed paraganglioma in a 58-year-old female who underwent tumor resection. The patient became severely hypertensive intraoperatively with paroxysmal swings in blood pressure and then later became acutely hypotensive after tumor removal. She was managed in the surgical intensive care unit (SICU) postoperatively and discharged from the hospital without acute complications. We briefly discuss the epidemiology, clinical presentation, perioperative management, and possible complications of these tumors to assist healthcare providers if one were to encounter them.Item Open Access Cerebrospinal Fluid Proteome Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction.(Journal of Alzheimer's disease : JAD, 2021-02-26) VanDusen, Keith W; Li, Yi-Ju; Cai, Victor; Hall, Ashley; Hiles, Sarah; Thompson, J Will; Moseley, M Arthur; Cooter, Mary; Acker, Leah; Levy, Jerrold H; Ghadimi, Kamrouz; Quiñones, Quintin J; Devinney, Michael J; Chung, Stacey; Terrando, Niccolò; Moretti, Eugene W; Browndyke, Jeffrey N; Mathew, Joseph P; Berger, Miles; MADCO-PC InvestigatorsBackground
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.Item Open Access Noninvasive monitoring of tissue hemoglobin using UV-VIS diffuse reflectance spectroscopy: a pilot study.(Opt Express, 2009-12-21) Bender, Janelle E; Shang, Allan B; Moretti, Eugene W; Yu, Bing; Richards, Lisa M; Ramanujam, NirmalaWe conducted a pilot study on 10 patients undergoing general surgery to test the feasibility of diffuse reflectance spectroscopy in the visible wavelength range as a noninvasive monitoring tool for blood loss during surgery. Ratios of raw diffuse reflectance at wavelength pairs were tested as a first-pass for estimating hemoglobin concentration. Ratios can be calculated easily and rapidly with limited post-processing, and so this can be considered a near real-time monitoring device. We found the best hemoglobin correlations were when ratios at isosbestic points of oxy- and deoxyhemoglobin were used, specifically 529/500 nm. Baseline subtraction improved correlations, specifically at 520/509 nm. These results demonstrate proof-of-concept for the ability of this noninvasive device to monitor hemoglobin concentration changes due to surgical blood loss. The 529/500 nm ratio also appears to account for variations in probe pressure, as determined from measurements on two volunteers.Item Open Access Perioperative neurocognitive and functional neuroimaging trajectories in older APOE4 carriers compared with non-carriers: secondary analysis of a prospective cohort study(British Journal of Anaesthesia, 2021-09) Browndyke, Jeffrey N; Wright, Mary C; Yang, Rosa; Syed, Ayesha; Park, John; Hall, Ashley; Martucci, Katherine; Devinney, Michael J; Shaw, Leslie; Waligorska, Teresa; Moretti, Eugene W; Whitson, Heather E; Cohen, Harvey J; Mathew, Joseph P; Berger, Miles; MADCO-PC InvestigatorsItem Open Access Postoperative changes in cognition and cerebrospinal fluid neurodegenerative disease biomarkers.(Annals of clinical and translational neurology, 2022-02) Berger, Miles; Browndyke, Jeffrey N; Cooter Wright, Mary; Nobuhara, Chloe; Reese, Melody; Acker, Leah; Bullock, W Michael; Colin, Brian J; Devinney, Michael J; Moretti, Eugene W; Moul, Judd W; Ohlendorf, Brian; Laskowitz, Daniel T; Waligorska, Teresa; Shaw, Leslie M; Whitson, Heather E; Cohen, Harvey J; Mathew, Joseph P; MADCO-PC InvestigatorsObjective
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).Item Open Access The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.(Journal of Alzheimer's disease : JAD, 2020-01) VanDusen, Keith W; Eleswarpu, Sarada; Moretti, Eugene W; Devinney, Michael J; Crabtree, Donna M; Laskowitz, Daniel T; Woldorff, Marty G; Roberts, Kenneth C; Whittle, John; Browndyke, Jeffrey N; Cooter, Mary; Rockhold, Frank W; Anakwenze, Oke; Bolognesi, Michael P; Easley, Mark E; Ferrandino, Michael N; Jiranek, William A; Berger, Miles; MARBLE Study InvestigatorsBACKGROUND: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.