665 results on '"Maze M"'
Search Results
202. Interleukin-6 is both necessary and sufficient to produce perioperative neurocognitive disorder in mice.
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Hu, J., Feng, X., Valdearcos, M., Lutrin, D., Uchida, Y., Koliwad, S. K., and Maze, M.
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INTERLEUKIN-6 , *NEUROPHYSIOLOGY , *THERAPEUTIC use of cytokines , *THERAPEUTICS - Abstract
Background: Perioperative neurocognitive disorders (PND) result in long-term morbidity and mortality with no effective interventions available. Because interleukin-6 (IL-6), a pro-inflammatory cytokine, is consistently up-regulated by trauma, including after surgery, we determined whether IL-6 is a putative therapeutic target for PND in a mouse model.Methods: Following institutional approval, adult (12-14 weeks) male C57/Bl6 mice were pretreated with the IL-6 receptor (IL6R) blocking antibody tocilizumab prior to open tibia fracture with internal fixation under isoflurane anaesthesia. Inflammatory and behavioural responses in a trace fear conditioning (TFC) paradigm were assessed postoperatively. Separately, the effects of IL-6 administration or of depletion of bone marrow-derived monocytes (BM-DMs) with clodrolip on the inflammatory and behavioural responses were assessed. Blood brain barrier disruption, hippocampal microglial activation, and infiltration of BM-DMs were each assessed following IL-6 administration.Results: The surgery-induced decrement in freezing time in the TFC assay, indicative of cognitive decline, was attenuated by tocilizumab (P<0.01). The surgery-induced increase in pro-inflammatory mediators was significantly reduced by tocilizumab. Exogenously administered IL-6 significantly impaired freezing behaviour (P<0.05) and up-regulated pro-inflammatory cytokines; both responses were prevented by depletion of BM-DMs. IL-6 disrupted the blood brain barrier, and increased hippocampal activation of microglia and infiltration of BM-DMs.Conclusions: IL-6 is both necessary and sufficient to produce cognitive decline. Following further preclinical testing of its perioperative safety, the IL6R blocker tocilizumab is a candidate for prevention and/or treatment of PND. [ABSTRACT FROM AUTHOR]- Published
- 2018
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203. The hip fracture surgery in elderly patients (HIPELD) study to evaluate xenon anaesthesia for the prevention of postoperative delirium: a multicentre, randomized clinical trial
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H. van Oven, Manuella Schaller, Vincent Minville, Nadia Rosencher, Peter Kienbaum, J.A. Carbonell, Andrea Tognù, Mathias Knobe, Pina Gallerani, M.S. Schaefer, Dina Kuschka, Marc Felzen, P. Kienbaum, Irene León, Layth Al Tmimi, Luc Eyrolle, Rolf Rossaint, B. Garrigues, M. Coburn, Greta Fini, Marina Soro, Mark Coburn, G.M. Arnold, Sarah Devroe, Christian Stoppe, Patrick Jacquinot, Olivier Langeron, O. Langeron, Steffen Rex, Barbara Rossi, Maximilian S. Schaefer, M. Maze, Marie Paries, Martin Neukirchen, Beatriz Garrigues, J. Hernadez, Aurora Guglielmetti, M. Neukirchen, Oliver Kunitz, Battista Borghi, Benjamin Graham, Sabine Roche, Patrick Doyle, My-Liên Nguyên-Pascal, Francisco Javier Belda, Ana Stevanovic, Glenn Arnold, Maria Luisa Garcia-Perez, Astrid V. Fahlenkamp, Nina Gaza, A. Stevanovic, Xavier Capdevila, P. Albaladejo, M. Schaller, Mervyn Maze, Hanna van Oven, M.-L. Nguyên-Pascal, Thorsten Eisenach, Bea Bastin, Fabrice Ferré, Marc Van de Velde, S. Rex, Robert Sanders, B. Borghi, L. Al tmimi, X. Capdevila, A. Tognù, L. Eyrolle, Carlos Ferrando, Marisa Luisa Garcia-Perez, R. Rossaint, Robert D. Sanders, José A. Carbonell, Coburn, M, Sanders, R D, Maze, M, Nguyên-Pascal, M-L, Rex, S, Garrigues, B, Carbonell, J A, Garcia-Perez, M L, Stevanovic, A, Kienbaum, P, Neukirchen, M, Schaefer, M S, Borghi, B, van Oven, H, Tognù, A, Al Tmimi, L, Eyrolle, L, Langeron, O, Capdevila, X, Arnold, G M, Schaller, M, and Rossaint, R
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Male ,Aging ,Xenon ,law.invention ,0302 clinical medicine ,Emergence Delirium ,Randomized controlled trial ,030202 anesthesiology ,law ,Anesthesiology ,80 and over ,Anesthesia ,General anaesthesia ,Orthopedic Procedures ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,Aged, 80 and over ,Hip fracture ,Incidence ,Rehabilitation ,anaesthesia ,aged ,Mental Health ,Treatment Outcome ,Inhalation ,Emergence delirium ,hip fracture ,6.1 Pharmaceuticals ,Anesthetics, Inhalation ,Female ,Patient Safety ,medicine.symptom ,6.4 Surgery ,anaesthesia, general ,medicine.medical_specialty ,Physical Injury - Accidents and Adverse Effects ,Clinical Trials and Supportive Activities ,Clinical Sciences ,and over ,03 medical and health sciences ,Sevoflurane ,delirium ,Clinical Research ,medicine ,Humans ,Adverse effect ,Anesthetics ,business.industry ,Hip Fractures ,Evaluation of treatments and therapeutic interventions ,medicine.disease ,xenon ,Anesthesiology and Pain Medicine ,general ,Osteoporosis ,Delirium ,HIPELD Study Investigators ,business ,Anesthesia, Inhalation - Abstract
Background Postoperative delirium occurs frequently in elderly hip fracture surgery patients and is associated with poorer overall outcomes. Because xenon anaesthesia has neuroprotective properties, we evaluated its effect on the incidence of delirium and other outcomes after hip fracture surgery. Methods This was a phase II, multicentre, randomized, double-blind, parallel-group, controlled clinical trial conducted in hospitals in six European countries (September 2010 to October 2014). Elderly (≥75yr-old) and mentally functional hip fracture patients were randomly assigned 1:1 to receive either xenon- or sevoflurane-based general anaesthesia during surgery. The primary outcome was postoperative delirium diagnosed through postoperative day 4. Secondary outcomes were delirium diagnosed anytime after surgery, postoperative sequential organ failure assessment (SOFA) scores, and adverse events (AEs). Results Of 256 enrolled patients, 124 were treated with xenon and 132 with sevoflurane. The incidence of delirium with xenon (9.7% [95% CI: 4.5 -14.9]) or with sevoflurane (13.6% [95% CI: 7.8 -19.5]) were not significantly different (P=0.33). Overall SOFA scores were significantly lower with xenon (least-squares mean difference: −0.33 [95% CI: −0.60 to −0.06]; P=0.017). For xenon and sevoflurane, the incidence of serious AEs and fatal AEs was 8.0% vs 15.9% (P=0.05) and 0% vs 3.8% (P=0.06), respectively. Conclusions Xenon anaesthesia did not significantly reduce the incidence of postoperative delirium after hip fracture surgery. Nevertheless, exploratory observations concerning postoperative SOFA-scores, serious AEs, and deaths warrant further study of the potential benefits of xenon anaesthesia in elderly hip fracture surgery patients. Clinical trial registration EudraCT 2009-017153-35; ClinicalTrials.gov NCT01199276.
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- 2018
204. Adjunctive intravenous then oral vitamin C for moderate and severe community-acquired pneumonia in hospitalized adults: Feasibility of randomized controlled trial
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Chambers, ST, Storer, M, Scott-Thomas, A, Slow, Sandra-Marie, Williman, J, Epton, M, Murdoch, DR, Metcalf, S, Carr, A, Isenman, H, and Maze, M
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205. Effect of remimazolam besylate vs propofol on incidence of postoperative delirium in older patients undergoing hip surgery: a randomized Non-inferiority trial.
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Fang PP, Hu J, Wei QF, Liang YJ, Fan YG, Shen QY, Lu Y, Liu XS, and Maze M
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- 2024
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206. Neuroprotective Effects of Inhaled Xenon Gas on Brain Structural Gray Matter Changes After Out-of-Hospital Cardiac Arrest Evaluated by Morphometric Analysis: A Substudy of the Randomized Xe-Hypotheca Trial.
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Hollmén C, Parkkola R, Vorobyev V, Saunavaara J, Laitio R, Arola O, Hynninen M, Bäcklund M, Martola J, Ylikoski E, Roine RO, Tiainen M, Scheinin H, Maze M, Vahlberg T, and Laitio TT
- Abstract
Background: We have earlier reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). A predefined secondary objective was to assess the effect of inhaled xenon on the structural changes in gray matter in comatose survivors after OHCA., Methods: Patients were randomly assigned to receive either inhaled xenon combined with target temperature management (33 °C) for 24 h (n = 55, xenon group) or target temperature management alone (n = 55, control group). A change of brain gray matter volume was assessed with a voxel-based morphometry evaluation of high-resolution structural brain magnetic resonance imaging (MRI) data with Statistical Parametric Mapping. Patients were scheduled to undergo the first MRI between 36 and 52 h and a second MRI 10 days after OHCA., Results: Of the 110 randomly assigned patients in the Xe-Hypotheca trial, 66 patients completed both MRI scans. After all imaging-based exclusions, 21 patients in the control group and 24 patients in the xenon group had both scan 1 and scan 2 available for analyses with scans that fulfilled the quality criteria. Compared with the xenon group, the control group had a significant decrease in brain gray matter volume in several clusters in the second scan compared with the first. In a between-group analysis, significant reductions were found in the right amygdala/entorhinal cortex (p = 0.025), left amygdala (p = 0.043), left middle temporal gyrus (p = 0.042), left inferior temporal gyrus (p = 0.008), left parahippocampal gyrus (p = 0.042), left temporal pole (p = 0.042), and left cerebellar cortex (p = 0.005). In the remaining gray matter areas, there were no significant changes between the groups., Conclusions: In comatose survivors of OHCA, inhaled xenon combined with targeted temperature management preserved gray matter better than hypothermia alone., Clinical Trial Registration: ClinicalTrials.gov: NCT00879892., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)
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- 2024
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207. Estimation of methane greenhouse gas emissions from livestock in Egypt during 1989 to 2021.
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Maze M, Taqi MO, Tolba R, Abdel-Wareth AAA, and Lohakare J
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- Animals, Egypt, Manure analysis, Cattle, Sheep, Environmental Monitoring methods, Methane analysis, Methane metabolism, Greenhouse Gases analysis, Livestock
- Abstract
This study investigates methane emissions from the livestock sector, representing by enteric fermentation and manure management, in Egypt from 1989 to 2021, focusing on spatial and temporal variations at the governorate level. Utilizing IPCC guidelines and emission factors, methane emissions were estimated for dairy and non-dairy cattle, buffalo, sheep and goat, poultry, and other livestock categories. Results reveal fluctuating emission patterns over the study period, with notable declines in certain governorates such as Kafr El-Sheikh and Red Sea, attributed to reductions in livestock populations. However, increasing trends were observed overall, driven by population growth in other regions. Hotspots of methane emissions were identified in delta governorates like Behera and Sharkia, as well as agriculturally rich regions including Menia and Suhag. While livestock populations varied between regions, factors such as water availability, climatic conditions, and farming practices influenced distribution. Notably, cluster analysis did not reveal regional clustering among governorates, suggesting emissions changes were not dependent on specific geographic or climatic boundaries. Manure management accounted for only 5-6% of total emissions, with emissions at their lowest in the last three years due to population declines. Despite the highest livestock populations being sheep and goats, emissions from enteric fermentation and manure management were highest from buffalo and cattle. This study underscores the importance of accurate data collection and adherence to IPCC recommendations for estimating GHG emissions, enabling the development of targeted mitigation strategies to address climate change challenges in the livestock sector., (© 2024. The Author(s).)
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- 2024
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208. The role of cultural competency training to address health disparities in surgical settings.
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Mora R and Maze M
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- Humans, General Surgery education, Cultural Competency education, Healthcare Disparities
- Abstract
Background: Disparities in health care delivered to marginalized groups are unjust and result in poor health outcomes that increase the cost of care for everyone. These disparities are largely avoidable and health care providers, have been targeted with education and specialised training to address these disparities., Sources of Data: In this manuscript we have sought out both peer-reviewed material on Pubmed, as well as policy statements on the potential role of cultural competency training (CCT) for providers in the surgical care setting. The goal of undertaking this work was to determine whether there is evidence that these endeavours are effective at reducing disparities., Areas of Agreement: The unjustness of health care disparities is universally accepted., Areas of Controversy: Whether the outcome of CCT justifies the cost has not been effectively answered., Growing Points: These include the structure/content of the CCT and whether the training should be delivered to teams in the surgical setting., Areas Timely for Developing Research: Because health outcomes are affected by many different inputs, should the effectiveness of CCT be improvement in health outcomes or should we use a proxy or a surrogate of health outcomes., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2024
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209. ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.
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Pan JZ, Wang Z, Sun W, Pan P, Li W, Sun Y, Chen S, Lin A, Tan W, He L, Greene J, Yao V, An L, Liang R, Li Q, Yu J, Zhang L, Kyritsis N, Fernandez XD, Moncivais S, Mendoza E, Fung P, Wang G, Niu X, Du Q, Xiao Z, Chang Y, Lv P, Huie JR, Torres-Espin A, Ferguson AR, Hemmerle DD, Talbott JF, Weinstein PR, Pascual LU, Singh V, DiGiorgio AM, Saigal R, Whetstone WD, Manley GT, Dhall SS, Bresnahan JC, Maze M, Jiang X, Singhal NS, Beattie MS, Su H, and Guan Z
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- Animals, Female, Humans, Male, Mice, Disease Models, Animal, Mice, Knockout, Activating Transcription Factor 3 metabolism, Activating Transcription Factor 3 genetics, Biomarkers metabolism, Biomarkers blood, Ischemic Stroke metabolism, Ischemic Stroke genetics, Ischemic Stroke blood, Neurons metabolism, Spinal Cord Injuries metabolism, Spinal Cord Injuries genetics, Spinal Cord Injuries complications
- Abstract
Background: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions., Methods: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits., Results: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function., Conclusions: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties., Highlights: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)
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- 2024
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210. Clinical Use of Adrenergic Receptor Ligands in Acute Care Settings.
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Langnas E and Maze M
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- Humans, Ligands, Adrenergic Antagonists pharmacology, Adrenergic Antagonists therapeutic use, Animals, Critical Care, Adrenergic Agonists pharmacology, Adrenergic Agonists therapeutic use, Receptors, Adrenergic metabolism, Receptors, Adrenergic drug effects
- Abstract
In this chapter, we review how ligands, both agonists and antagonists, for the major classes of adrenoreceptors, are utilized in acute care clinical settings. Adrenergic ligands exert their effects by interacting with the three major classes of adrenoceptors. Adrenoceptor agonists and antagonists have important applications, ranging from treatment of hypotension to asthma, and have proven to be extremely useful in a variety of clinical settings of acute care from the operating room to the critical care environment. Continued research interpreting the mechanisms of adrenoreceptors may help the discovery of new drugs with more desirable clinical profiles., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
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- 2024
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211. Resolution of elevated interleukin-6 after surgery is associated with return of normal cognitive function.
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Taylor J, Wu JG, Kunkel D, Parker M, Rivera C, Casey C, Naismith S, Teixeira-Pinto A, Maze M, Pearce RA, Lennertz R, and Sanders RD
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- Humans, Aged, Prospective Studies, Cognition, Neuropsychological Tests, Inflammation, Interleukin-6, Cognitive Dysfunction etiology
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Background: Unresolved surgical inflammation might induce chronic cognitive decline in older adults. Although inflammatory biomarkers have been correlated with perioperative cognitive impairment and delirium, the effects of prolonged inflammation on cognition are not well studied. This prospective cohort study investigated 1-yr dynamics in plasma interleukin-6 levels and executive function., Methods: Patients undergoing major surgery (n=170) aged ≥65 yr completed Trail Making Test B and other neuropsychological assessments with plasma interleukin-6 levels collected on postoperative days 1-9 and 90, and at 1-yr. Mixed-effects analyses were conducted for Trail Making Test B (and other assessments), including interleukin-6 levels, time, and additional confounders (fixed effects), and a random effect for participant., Results: Changes in interleukin-6 levels were associated with changes in Trail Making Test B over 1 yr in a generalised additive model (β=0.074, P<0.001) supporting that unresolved inflammation impaired executive function. This result was robust to confounders, outlier rejection, and fitting to non-linear models. Changes in interleukin-6 levels also correlated with changes in Trail Making Test A and Controlled Oral Word Association Test. Sensitivity analyses conducted on binary definitions of cognitive decline (>1, >1.5, or >2 standard deviations from baseline) were also associated with interleukin-6 changes., Conclusions: Delayed resolution of inflammation is associated with cognitive impairment after surgery. Monitoring interleukin-6 might provide an opportunity to intervene with anti-inflammatory therapies in vulnerable patients., Clinical Trial Registration: NCT01980511, NCT03124303., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
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212. Low Vitamin C Concentrations in Patients with Community-Acquired Pneumonia Resolved with Pragmatic Administration of Intravenous and Oral Vitamin C.
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Carr AC, Vlasiuk E, Zawari M, Scott-Thomas A, Storer M, Maze M, and Chambers ST
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Community-acquired pneumonia (CAP) is characterized by elevated markers of inflammation and oxidative stress and depleted circulating concentrations of the antioxidant nutrient vitamin C. A feasibility trial of intravenous and oral vitamin C supplementation, matched to the timing of intravenous and oral antibiotic formulations, was carried out and changes in vitamin C status were monitored to determine whether saturating status could be achieved throughout the administration period. Patients with moderate and severe CAP (CURB-65 ≥ 2; n = 75) who were receiving intravenous antimicrobial therapy were randomized to placebo ( n = 39) or intravenous vitamin C (2.5 g per 8 h; n = 36) before moving to oral vitamin C (1 g three times daily) when prescribed oral antimicrobials. Blood samples were collected at baseline and then daily whilst in the hospital. Vitamin C concentrations were determined by high-performance liquid chromatography. The inflammatory and infection biomarkers C-reactive protein and procalcitonin were elevated at baseline (158 (61, 277) mg/L and 414 (155, 1708) ng/L, respectively), and vitamin C concentrations were depleted (15 (7, 25) µmol/L). There was an inverse association between vitamin C and C-reactive protein concentrations ( r = -0.312, p = 0.01). Within one day of intervention initiation, plasma vitamin C concentrations in the vitamin C group reached median concentrations of 227 (109, 422) µmol/L, and circulating concentrations remained at ≥150 µmol/L for the duration of the intervention, whilst median vitamin C concentrations in the placebo group remained low (≤35 µmol/L). There was a trend toward decreased duration of hospital stay ( p = 0.07) and time to clinical stability ( p = 0.08) in the vitamin C group. In conclusion, patients with moderate to severe CAP have inadequate plasma vitamin C concentrations for the duration of their hospital stay. The administration of intravenous or oral vitamin C, titrated to match the antimicrobial formulation, provided saturating plasma vitamin C concentrations whilst in the hospital. There were trends toward shorter duration of hospital stay and time to clinical stability. Thus, larger trials assessing the impact of intravenous and oral vitamin C intervention on CAP clinical outcomes are indicated.
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- 2023
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213. Adjunctive intravenous then oral vitamin C for moderate and severe community-acquired pneumonia in hospitalized adults: feasibility of randomized controlled trial.
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Chambers ST, Storer M, Scott-Thomas A, Slow S, Williman J, Epton M, Murdoch DR, Metcalf S, Carr A, Isenman H, and Maze M
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- Adult, Humans, Male, Aged, Female, Feasibility Studies, Vitamins, Infusions, Intravenous, Ascorbic Acid therapeutic use, Pneumonia drug therapy
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Patients hospitalised with community acquired pneumonia (CAP) have low peripheral blood vitamin C concentrations and limited antioxidant capacity. The feasibility of a trial of vitamin C supplementation to improve patient outcomes was assessed. Participants with moderate and severe CAP (CURB-65 ≥ 2) on intravenous antimicrobial treatment were randomised to either intravenous vitamin C (2.5 g 8 hourly) or placebo before switching to oral intervention (1 g tds) for 7 days when they were prescribed oral antimicrobial therapy. Of 344 patients screened 75 (22%) were randomised and analysed. The median age was 76 years, and 43 (57%) were male. In each group, one serious adverse event that was potentially intervention related occurred, and one subject discontinued treatment. Vitamin C concentrations were 226 µmol/L in the vitamin C group and 19 µmol/L in the placebo group (p < 0.001) after 3 intravneous doses. There were no signficant differences between the vitamin C and placebo groups for death within 28 days (0 vs. 2; p = 0.49), median length of stay (69 vs. 121 h; p = 0.07), time to clinical stability (22 vs. 49 h; p = 0.08), or readmission within 30 days (1 vs. 4; p = 0.22). The vitamin C doses given were safe, well tolerated and saturating. A randomised controlled trial to assess the efficacy of vitamin C in patients with CAP would require 932 participants (CURB-65 ≥ 2) to observe a difference in mortality and 200 participants to observe a difference with a composite endpoint such as mortality plus discharge after 7 days in hospital. These studies are feasible in a multicentre setting., (© 2023. The Author(s).)
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- 2023
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214. High Mobility Group Box 1 (HMGB1): Potential Target in Sepsis-Associated Encephalopathy.
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DeWulf B, Minsart L, Verdonk F, Kruys V, Piagnerelli M, Maze M, and Saxena S
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- Humans, Alarmins, Sepsis-Associated Encephalopathy diagnosis, HMGB1 Protein, Sepsis complications, Sepsis pathology, Brain Diseases
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Sepsis-associated encephalopathy (SAE) remains a challenge for intensivists that is exacerbated by lack of an effective diagnostic tool and an unambiguous definition to properly identify SAE patients. Risk factors for SAE development include age, genetic factors as well as pre-existing neuropsychiatric conditions. Sepsis due to certain infection sites/origins might be more prone to encephalopathy development than other cases. Currently, ICU management of SAE is mainly based on non-pharmacological support. Pre-clinical studies have described the role of the alarmin high mobility group box 1 (HMGB1) in the complex pathogenesis of SAE. Although there are limited data available about the role of HMGB1 in neuroinflammation following sepsis, it has been implicated in other neurologic disorders, where its translocation from the nucleus to the extracellular space has been found to trigger neuroinflammatory reactions and disrupt the blood-brain barrier. Negating the inflammatory cascade, by targeting HMGB1, may be a strategy to complement non-pharmacologic interventions directed against encephalopathy. This review describes inflammatory cascades implicating HMGB1 and strategies for its use to mitigate sepsis-induced encephalopathy.
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- 2023
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215. Paradoxical increases in anterior cingulate cortex activity during nitrous oxide-induced analgesia reveal a signature of pain affect.
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Weinrich JA, Liu CD, Jewell ME, Andolina CR, Bernstein MX, Benitez J, Rodriguez-Rosado S, Braz JM, Maze M, Nemenov MI, and Basbaum AI
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The general consensus is that increases in neuronal activity in the anterior cingulate cortex (ACC) contribute to pain's negative affect. Here, using in vivo imaging of neuronal calcium dynamics in mice, we report that nitrous oxide, a general anesthetic that reduces pain affect, paradoxically, increases ACC spontaneous activity. As expected, a noxious stimulus also increased ACC activity. However, as nitrous oxide increases baseline activity, the relative change in activity from pre-stimulus baseline was significantly less than the change in the absence of the general anesthetic. We suggest that this relative change in activity represents a neural signature of the affective pain experience. Furthermore, this signature of pain persists under general anesthesia induced by isoflurane, at concentrations in which the mouse is unresponsive. We suggest that this signature underlies the phenomenon of connected consciousness, in which use of the isolated forelimb technique revealed that pain percepts can persist in anesthetized patients.
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- 2023
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216. Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes.
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Saxena S, Nuyens V, Rodts C, Jamar K, Albert A, Seidel L, Cherkaoui-Malki M, Boogaerts JG, Wulff H, Maze M, Kruys V, and Vamecq J
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- Mice, Animals, Interleukin-6, Neurocognitive Disorders, Cognition, Mice, Inbred C57BL, Neuroinflammatory Diseases, HMGB1 Protein
- Abstract
Background: Potassium channels (KCa3.1; Kv1.3; Kir2.1) are necessary for microglial activation, a pivotal requirement for the development of Perioperative Neurocognitive Disorders (PNDs). We previously reported on the role of microglial Kv1.3 for PNDs; the present study sought to determine whether inhibiting KCa3.1 channel activity affects neuroinflammation and prevents development of PND., Methods: Mice (wild-type [WT] and KCa3.1
-/- ) underwent aseptic tibial fracture trauma under isoflurane anesthesia or received anesthesia alone. WT mice received either TRAM34 (a specific KCa3.1 channel inhibitor) dissolved in its vehicle (miglyol) or miglyol alone. Spatial memory was assessed in the Y-maze paradigm 6 h post-surgery/anesthesia. Circulating interleukin-6 (IL-6) and high mobility group box-1 protein (HMGB1) were assessed by ELISA, and microglial activitation Iba-1 staining., Results: In WT mice surgery induced significant cognitive decline in the Y-maze test, p = 0.019), microgliosis (p = 0.001), and increases in plasma IL-6 (p = 0.002) and HMGB1 (p = 0.001) when compared to anesthesia alone. TRAM34 administration attenuated the surgery-induced changes in cognition, microglial activation, and HMGB1 but not circulating IL-6 levels. In KCa3.1-/- mice surgery neither affected cognition nor microgliosis, although circulating IL-6 levels did increase (p < 0.001)., Conclusion: Similar to our earlier report with Kv1.3, perioperative microglial KCa3.1 blockade decreases immediate perioperative cognitive changes, microgliosis as well as the peripheral trauma marker HMGB1 although surgery-induced IL-6 elevation was unchanged. Future research should address whether a synergistic interaction exists between blockade of Kv1.3 and KCa3.1 for preventing PNDs., (© 2023. The Author(s).)- Published
- 2023
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217. Contribution of intraoperative electroencephalogram suppression to frailty-associated postoperative delirium: mediation analysis of a prospective surgical cohort.
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Fang PP, Shang ZX, Xu J, Hu J, Zhang SC, Fan YG, Lu Y, Liu XS, and Maze M
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- Humans, Aged, Prospective Studies, Mediation Analysis, Risk Factors, Electroencephalography, Postoperative Complications diagnosis, Emergence Delirium, Frailty diagnosis, Frailty complications, Delirium etiology
- Abstract
Background: Frailty is a risk factor for postoperative delirium (POD), and has led to preoperative interventions that have reduced, but not eliminated, the risk. We hypothesised that EEG suppression, another risk factor for POD, mediates some of the frailty risk for POD., Methods: A prospective cohort study enrolled patients aged 65 yr or older, scheduled for noncardiac surgery under total intravenous anaesthesia. Frailty was assessed using the FRAIL scale. Cumulative duration of EEG suppression, defined as an amplitude between -5 and 5 μV for >0.5 s during anaesthesia, was measured. POD was diagnosed by either confusion assessment method (CAM), CAM-ICU, or medical records. The severity of POD was assessed using the Delirium Rating Scale - Revised-98 (DRS). Mediation analysis was used to estimate the relationships between frailty, EEG suppression, and severity of POD., Results: Among 252 enrolled patients, 51 were robust, 129 were prefrail, and 72 were frail. Patients classified as frail had higher duration of EEG suppression than either the robust (19 vs 0.57 s, P<0.001) or prefrail groups (19 vs 3.22 s, P<0.001). Peak delirium score was higher in the frail group than either the robust (17 vs 15, P<0.001) or prefrail groups (17 vs 16, P=0.007). EEG suppression time mediated 24.2% of the frailty-DRS scores association., Conclusion: EEG suppression time mediated a statistically significant portion of the frailty-POD association in older noncardiac surgery patients. Trials directed at reducing EEG suppression time could result in intraoperative interventions to reduce POD in frail patients., Clinical Trial Registration: ChiCTR2000041092 (Chinese Clinical Trial Registry)., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)
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- 2023
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218. Comparison of the prognostic value of early-phase proton magnetic resonance spectroscopy and diffusion tensor imaging with serum neuron-specific enolase at 72 h in comatose survivors of out-of-hospital cardiac arrest-a substudy of the XeHypotheca trial.
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Koskensalo K, Virtanen S, Saunavaara J, Parkkola R, Laitio R, Arola O, Hynninen M, Silvasti P, Nukarinen E, Martola J, Silvennoinen HM, Tiainen M, Roine RO, Scheinin H, Saraste A, Maze M, Vahlberg T, and Laitio TT
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- Humans, Biomarkers, Diffusion Tensor Imaging, Phosphopyruvate Hydratase, Prognosis, Proton Magnetic Resonance Spectroscopy, Seizures, Survivors, Coma diagnostic imaging, Out-of-Hospital Cardiac Arrest diagnostic imaging, Out-of-Hospital Cardiac Arrest therapy, Out-of-Hospital Cardiac Arrest pathology
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Purpose: We compared the predictive accuracy of early-phase brain diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS), and serum neuron-specific enolase (NSE) against the motor score and epileptic seizures (ES) for poor neurological outcome after out-of-hospital cardiac arrest (OHCA)., Methods: The predictive accuracy of DTI, 1H-MRS, and NSE along with motor score at 72 h and ES for the poor neurological outcome (modified Rankin Scale, mRS, 3 - 6) in 92 comatose OHCA patients at 6 months was assessed by area under the receiver operating characteristic curve (AUROC). Combined models of the variables were included as exploratory., Results: The predictive accuracy of fractional anisotropy (FA) of DTI (AUROC 0.73, 95% CI 0.62-0.84), total N-acetyl aspartate/total creatine (tNAA/tCr) of 1H-MRS (0.78 (0.68 - 0.88)), or NSE at 72 h (0.85 (0.76 - 0.93)) was not significantly better than motor score at 72 h (0.88 (95% CI 0.80-0.96)). The addition of FA and tNAA/tCr to a combination of NSE, motor score, and ES provided a small but statistically significant improvement in predictive accuracy (AUROC 0.92 (0.85-0.98) vs 0.98 (0.96-1.00), p = 0.037)., Conclusion: None of the variables (FA, tNAA/tCr, ES, NSE at 72 h, and motor score at 72 h) differed significantly in predicting poor outcomes in this patient group. Early-phase quantitative neuroimaging provided a statistically significant improvement for the predictive value when combined with ES and motor score with or without NSE. However, in clinical practice, the additional value is small, and considering the costs and challenges of imaging in this patient group, early-phase DTI/MRS cannot be recommended for routine use., Trial Registration: ClinicalTrials.gov NCT00879892, April 13, 2009., (© 2022. The Author(s).)
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- 2023
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219. Defining the role of Interleukin-6 for the development of perioperative neurocognitive disorders: Evidence from clinical and preclinical studies.
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Barreto Chang OL and Maze M
- Abstract
For most, staying "mentally sharp" as they age is a very high priority that may be thwarted by the consequences of a postoperative complication unrelated to the disorder which necessitated the surgical intervention. Perioperative neurocognitive disorder (PND) is an overarching term for cognitive impairment in surgical patients, that includes conditions from delirium to dementia, affecting more than 7 million patients annually in the US, and which threatens both functional independence and life. Clinical trials and meta-analyses have identified the association between PNDs and increased perioperative levels of Interleukin-6 (IL-6), a pleiotropic cytokine that is both necessary and sufficient for postoperative memory decline in a preclinical model of PND. Recently, we reported that, in adult male wild-type mice subjected to tibial fracture under general anesthesia, IL-6 trans-signaling in hippocampal CA1 neurons mediates surgery-induced memory impairment. As there are no therapeutic options for preventing or reversing PNDs, patients and their caregivers, as well as the healthcare industry, endure staggering costs. Olamkicept, a highly selective IL-6 trans-signaling blocker has shown to be efficacious and safe in clinical trials involving patients with inflammatory bowel disease, another condition for which IL-6 trans-signaling is the mediating mechanism. Subject to a demonstration that olamkicept is effective in preventing cognitive impairment in vulnerable (aged and Alzheimer's Disease) preclinical PND models, clinical trials involving aged and/or cognitively impaired surgical patients should be undertaken to study olamkicept's utility for PNDs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Barreto Chang and Maze.)
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- 2023
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220. Age-Related Perioperative Neurocognitive Disorders: Experimental Models and Druggable Targets.
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Barreto Chang OL, Possin KL, and Maze M
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- Animals, Humans, Neurocognitive Disorders drug therapy, Neurocognitive Disorders etiology, Models, Theoretical, Neuroinflammatory Diseases, Delirium
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With the worldwide increase in life span, surgical patients are becoming older and have a greater propensity for postoperative cognitive impairment, either new onset or through deterioration of an existing condition; in both conditions, knowledge of the patient's preoperative cognitive function and postoperative cognitive trajectory is imperative. We describe the clinical utility of a tablet-based technique for rapid assessment of the memory and attentiveness domains required for executive function. The pathogenic mechanisms for perioperative neurocognitive disorders have been investigated in animal models in which excessive and/or prolonged postoperative neuroinflammation has emerged as a likely contender. The cellular and molecular species involved in postoperative neuroinflammation are the putative targets for future therapeutic interventions that are efficacious and do not interfere with the surgical patient's healing process.
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- 2023
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221. Longitudinal Profiling of Plasma Cytokines and Its Association With Postoperative Delirium in Elderly Patients Undergoing Major Lower Limb Surgery: A Prospective Observational Study.
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Zhang Y, Hu J, Zuo W, He P, Xue Q, Feng X, Zhang Y, and Maze M
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- Humans, Aged, Middle Aged, Interleukin-6, Prospective Studies, Longitudinal Studies, Lower Extremity, Cytokines, Emergence Delirium
- Abstract
Background: Surgery is accompanied by a systemic inflammatory response that may presage delirium in susceptible individuals. Little is known about the trajectory of plasma proinflammatory cytokines and their potential associations with postoperative delirium (POD). The current study longitudinally assessed both pro and anti-inflammatory plasma cytokine response and development of POD in older surgical patients to investigate associations with individual and/or clusters of cytokines that may indicate pathogenic mechanisms., Methods: A prospective longitudinal study sought to enroll patients >60 years old who were scheduled for major lower limb surgery under general anesthesia. Blood was obtained preoperatively and postoperatively from day 1 through postoperative day 4 for measurement of plasma interleukin-1β (IL-1β), IL-2, IL-4, IL-6, soluble IL-6 receptor (sIL-6R), IL-10, and tumor necrosis factor-α (TNF-α). Participants were assessed for POD twice daily for 4 days using the confusion assessment method. Trajectory of postoperative changes in plasma cytokines was determined by a group-based trajectory modeling analysis that was informed by distinct cytokines identified by time-dependent Cox regression model., Results: One hundred eighty-eight patients were assessed for eligibility of whom 129 underwent major surgery and 126 had complete datasets for final analysis. POD was diagnosed in 31 of 126 patients (24.6%). Time-dependent Cox regression model identified that higher IL-6 and sIL-6R levels were associated with higher risk of developing POD. A two-cluster model (stable lower and fluctuating higher levels) was considered to be the most statistically appropriate model for IL-6 and sIL-6R trajectory. More participants with fluctuating higher IL-6 were delirious (73.3% vs 18.0%, P = .001) as were those with fluctuating higher sIL-6R (81.3% vs 16.4%, P = .001)., Conclusions: As higher IL-6 and sIL-6R levels were significantly associated with higher risk of POD and the combination is required for IL-6 trans-signaling, it is possible that activation of this pathway may be associated with POD. Furthermore, it will be important to determine whether high levels of the combination of IL-6 and sIL-6R can be an early biomarker for the subsequent development of POD., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)
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- 2023
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222. Interleukin-6 trans-signalling in hippocampal CA1 neurones mediates perioperative neurocognitive disorders in mice.
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Hu J, Zhang Y, Huang C, Feng X, He S, Zhang Y, and Maze M
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- Mice, Animals, Cytokine Receptor gp130 genetics, Cytokine Receptor gp130 metabolism, Receptors, Interleukin-6 metabolism, Hippocampus metabolism, Neurocognitive Disorders etiology, Interleukin-6 pharmacology, Tibial Fractures surgery
- Abstract
Background: Interleukin-6 (IL-6), a pleiotropic cytokine with both degenerative and regenerative properties, is necessary and sufficient to provoke perioperative neurocognitive disorders after aseptic trauma in mice. IL-6 initiates its actions after binding to either membrane-bound IL-6 receptor α (mIL-6Rα) through classical signalling, or soluble IL-6 receptor (IL-6R) through trans-signalling; both signalling pathways require the transducer gp130. We investigated the site and type of IL-6 signalling that pertains in a tibial fracture aseptic trauma model of perioperative neurocognitive disorder., Methods: Wild-type or genetically altered adult mice that lacked molecules unique to either classical or trans-IL-6 signalling underwent tibial fracture under isoflurane anaesthesia. In separate cohorts, we assessed postoperative memory using a trace fear conditioning paradigm (72 h postoperatively), and post-receptor IL-6 signalling (24 h postoperatively) using phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) in CA1 hippocampal neurones. Fracture healing was assessed at postoperative day 15 after inhibiting either both forms of IL-6 signalling with BE0047 or only trans-signalling with sgp130Fc., Results: The surgical phenotype of memory decline (decrease in freezing in trace fear conditioning) and upregulated IL-6 signalling (pSTAT3) did not occur after pretreatment before surgery with either BE0047 or sgp130Fc, or after depleting gp130 from CA1 neurones. The surgical phenotype still occurred when IL-6Rα was depleted in either CA1 hippocampal neurones (freezing time, 38.9% [11.5%] vs 58.4% [12.3%]; pSTAT
+ CA1 neurones, 31.7 [4.9] vs 7.0 [3.1]) or microglia (freezing time, 40.1% [13.9%] vs 65.2% [12.6%]; pSTAT+ CA1 neurones, 30.1 [5.5] vs 7.9 [3.2]). In global IL-6Rα-/- mice, hyper-IL-6, the trans-signalling agonist, produced the surgical phenotype when administered i.c.v. (freezing time, 42.4% [8.8%] vs 59.7% [10.4%]; pSTAT+ cells, 29.3 [4.3] vs 10.0 [4.4]). Bone-fracture healing (% of fracture callus comprised of new collagen) was significantly greater with sgp130Fc than with BE0047 (52.2% [8.3%] vs 39.7% [7.9%])., Conclusions: After orthopaedic trauma, IL-6 produces perioperative neurocognitive disorders through IL-6 trans-signalling in mouse CA1 neurones. Druggable targets of the trans-signalling pathway should be sought to reduce perioperative neurocognitive disorders while allowing the healing properties of classical IL-6 signalling., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2022
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223. Plasma fibrinogen: An important piece of the COVID-19 ICU delirium puzzle?
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Saxena S, Wery AR, Khelif A, Nisolle ML, Lelubre C, Maze M, Biston P, and Piagnerelli M
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Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2022
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224. Look Behind Me! Highly Informative Picture Backgrounds Increase Stated Generosity Through Perceived Tangibility, Impact, and Warm Glow.
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Caserotti M, Vacondio M, Maze M, and Priolo G
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In this study, we investigated whether background information of a visual charity appeal can influence people's motivation to donate and the hypothetical amount donated. Specifically, participants were presented with a charity appeal to help a local hospital respond to the Coronavirus Disease-19 (COVID-19) emergency depicting a man sitting on a bed in a hospital room. The number of visual details (i.e., medical equipment) depicted in the background was manipulated according to three conditions: (1) "High information" condition (i.e., a room full of medical equipment), (2) "low information" condition (i.e., room with few pieces of medical equipment), and (3) "no information" condition (i.e., non-contextual background). We investigated whether the number of visual background details would have increased the tangibility of the cause measured as the hospital's adequate preparedness to deal with the COVID-19 emergency and severity of the patient's medical conditions. We also investigated whether increased tangibility, elicited by a higher amount of background information, would heighten participants' perceived impact of their donation and warm glow, which in turn would have led to increased motivation to donate and the amount donated. We found no significant direct effect of condition on the donated amount. However, path models revealed that more background information positively influenced participants' motivation to donate and the amount donated indirectly through increased tangibility, impact, and warm glow. Finally, we showed that a higher risk perception of COVID-19 was associated with higher donations. Results are discussed in line with relevant literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Caserotti, Vacondio, Maze and Priolo.)
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- 2022
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225. Early postoperative risk prediction of neurocognitive decline.
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Saxena S, Rodts C, Nuyens V, Seidel L, Albert A, Boogaerts J, Kruys V, Maze M, and Vamecq J
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- Humans, Mental Status and Dementia Tests, Postoperative Period, Postoperative Complications etiology, Postoperative Complications psychology
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- 2022
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226. Considerations for the implementation of machine learning into acute care settings.
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Bishara A, Maze EH, and Maze M
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- Algorithms, Critical Care, Electronic Health Records, Humans, Artificial Intelligence, Machine Learning
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Introduction: Management of patients in the acute care setting requires accurate diagnosis and rapid initiation of validated treatments; therefore, this setting is likely to be an environment in which cognitive augmentation of the clinician's provision of care with technology rooted in artificial intelligence, such as machine learning (ML), is likely to eventuate., Sources of Data: PubMed and Google Scholar with search terms that included ML, intensive/critical care unit, electronic health records (EHR), anesthesia information management systems and clinical decision support were the primary sources for this report., Areas of Agreement: Different categories of learning of large clinical datasets, often contained in EHRs, are used for training in ML. Supervised learning uses algorithm-based models, including support vector machines, to pair patients' attributes with an expected outcome. Unsupervised learning uses clustering algorithms to define to which disease grouping a patient's attributes most closely approximates. Reinforcement learning algorithms use ongoing environmental feedback to deterministically pursue likely patient outcome., Areas of Controversy: Application of ML can result in undesirable outcomes over concerns related to fairness, transparency, privacy and accountability. Whether these ML technologies irrevocably change the healthcare workforce remains unresolved., Growing Points: Well-resourced Learning Health Systems are likely to exploit ML technology to gain the fullest benefits for their patients. How these clinical advantages can be extended to patients in health systems that are neither well-endowed, nor have the necessary data gathering technologies, needs to be urgently addressed to avoid further disparities in healthcare., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
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- 2022
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227. Dexmedetomidine for prevention of postoperative delirium in older adults undergoing oesophagectomy with total intravenous anaesthesia.
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Hu J, Zhang Y, and Maze M
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- Aged, Anesthesia, General, Anesthesia, Intravenous, Esophagectomy adverse effects, Humans, Delirium chemically induced, Delirium diagnosis, Delirium prevention & control, Dexmedetomidine adverse effects
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- 2022
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228. Adverse effects and duration of treatment of TB in Canterbury, New Zealand.
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Phillipson J, Kuruppu N, Chikura T, McLachlan C, McNeill L, Metcalf S, Pithie A, Rhodes B, Dalton S, and Maze MJ
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- Humans, Drug Monitoring, New Zealand epidemiology, Retrospective Studies, Duration of Therapy, Tuberculosis drug therapy, Antitubercular Agents adverse effects, Antitubercular Agents therapeutic use
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BACKGROUND Treatment of TB is often extended beyond the recommended duration. The aim of this study was to assess prevalence of extended treatment and to identify associated risk factors. We also aimed to determine the frequency and type of adverse drug reactions (ADR) experienced by this study population. METHODS We performed a retrospective cohort study of all patients treated for active TB at Christchurch Hospital, Christchurch, New Zealand, between 1 March 2012 and 31 December 2018. Data for 192 patients were collected on patient demographics, disease characteristics and treatment characteristics, including planned and actual duration of treatment and ADRs. RESULTS Of 192 patients, 35 (18.2%) had treatment extended, and 85 (46.5%) of 183 with fully drug-susceptible TB received ≥9 months treatment. The most common reasons for extension were persistent or extensive disease and ADR. Extended treatment duration was not associated with any patient or disease characteristics. We found 35 (18.2%) patients experienced at least one ADR. The most common ADRs were hepatitis, rash and peripheral neuropathy. CONCLUSION TB treatment extension beyond WHO guidelines is common. Further research is needed to guide management of those with slow response to treatment. Methods for early detection of ADR, systems to improve adherence and therapeutic drug monitoring are potentially useful strategies.
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- 2021
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229. Antimicrobial stewardship in human healthcare in Aotearoa New Zealand: urgent call for national leadership and co-ordinated efforts to preserve antimicrobial effectiveness.
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Gardiner SJ, Duffy EJ, Chambers ST, Thomas MG, Addidle M, Arnold B, Arroll B, Balm MN, Perales CB, Berger S, Best E, Betty B, Birch M, Blackmore TK, Bloomfield M, Briggs S, Bupha-Intr O, Burns A, Campbell C, Chin PK, Dalton SC, Davies N, Douglas NM, Plessis TD, Elvy J, Everts R, Green J, Grimwade K, Handy R, Hardie MG, Henderson E, Holland DJ, Howard J, Hudson B, Huggan P, Isenman H, Issa M, Kelly MJ, Li C, Lim AG, Lim J, Maze M, Metcalf SC, McCall C, Murdoch D, McRae G, Nisbet M, Pithie A, Raymond N, Read K, Restrepo D, Ritchie S, Robertson B, Ussher JE, Voss L, Walls T, and Sen Yew H
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- Humans, New Zealand, Anti-Bacterial Agents therapeutic use, Antimicrobial Stewardship organization & administration, Delivery of Health Care, Leadership
- Abstract
Competing Interests: Dr Murdoch reports he is a member of the panel for the Office of the Prime Minister’s Chief Science Advisor’s project on Antimicrobial Resistance and Infectious Diseases. Mr McRae reports he is a member of the New Zealand Antimicrobial Stewardship/Infection Pharmacist Expert Group, and a member of the Infection Prevention Advisory Group for ACC. Ms Mccall reports she is a member of the Canterbury District Health Board Hospital Antimicrobial Stewardship Committee. Dr Maze reports he is a member of the Canterbury District Health Board Hospital Antimicrobial Stewardship Committee. Ms Lim reports that she is a member of the New Zealand Antimicrobial Stewardship/Infection Pharmacist Expert Group and Southern District Health Board Antimicrobial Stewardship Committee. Miss Li reports that she is a member of the New Zealand Antimicrobial Stewardship/Infection Pharmacist Expert Group and a member of the Capital and Coast District Health Board Antimicrobial Stewardship Committee. Dr Kelly reports he is Chair of the National Infection Prevention and Control Expert Group, Ministry of Health. Mr Issa reports he is a member of the New Zealand Antimicrobial Stewardship/Infection Pharmacist Expert Group; a member of the Waikato District Health Board, Antimicrobial Steering Group; coordinator on the New Zealand Hospital Pharmacists’ Association – Infectious Disease/Antimicrobial Stewardship Special Interest Network; a member of the New Zealand Hospital Pharmacists’ Association; and a member of Pharmaceutical Society of New Zealand. Dr Howard reports involvement in writing antimicrobial guidelines at Waikato District Health Board. Mrs Hardie reports she is a member of the New Zealand Antimicrobial Stewardship/Infection Pharmacist Expert Group and member of the Waitematā District Health Board Antimicrobial Stewardship Committee. Dr Gardiner reports that she is co-lead for the New Zealand Antimicrobial Stewardship/Infection Pharmacist Expert Group; a member of the panel for the Office of the Prime Minister’s Chief Science Advisor’s project on Antimicrobial Resistance and Infectious Diseases; a member of the Steering Group for the ACC scoping report on developing national antimicrobial guidance for NZ; and Secretary of the Canterbury Antimicrobial Stewardship Strategic Group and Secretary of the CDHB Hospital Antimicrobial Stewardship Committee. Mr Duffy reports that he is co-lead for the New Zealand Antimicrobial Stewardship/Infection Pharmacist Expert Group; a member of the Ministry of Health AMR Co-ordination (HARC) Group; a member of the Steering Group for the ACC scoping report on developing national antimicrobial guidance for NZ; a member of the PTAC Anti-infective sub-committee (PHARMAC); and a member of Auckland DHB Antimicrobial Stewardship Committee. Ms du Plessis reports that she is Lead for the Counties-Manukau Hospital Antimicrobial Stewardship Program and Chair for the Counties-Manukau Hospital Antimicrobial Stewardship Committee. Dr Chambers reports being Deputy Chair of Canterbury District Health Board Hospital Antimicrobial Stewardship Committee; a member of the reference group for the Prime Minister’s Chief Science Advisor’s project on Antimicrobial Resistance and Infectious Diseases; and a member of PTAC Anti-infective sub-committee (PHARMAC). Dr Campbell reports that she is the Pharmaceutical Society of NZ representative on the NZ Antimicrobial Stewardship/Infection Pharmacist Expert Group; a member of the Ministry of Health Antimicrobial Resistance Coordination Group representing the Pharmaceutical Society of New Zealand; and a member of the Reference Group for the Office of the Prime Minister’s Chief Science Advisor’s project on Antimicrobial Resistance and Infectious Diseases. Dr Bupha-Intr reports that she is a member of the Capital and Coast DHB Antimicrobial Stewardship Committee. Dr Briggs reports that he is a member of the PTAC Anti-Infective Subcommittee (PHARMAC). Dr Birch reports being on the Canterbury District Health Board Hospital Antimicrobial Stewardship Committee. Dr Betty reports having provided advice to the panel for the Office of the Prime Minister’s Chief Science Advisor’s project on Antimicrobial Resistance and Infectious Diseases, and being Medical Director of the Royal NZ College of General Practice. Dr Batlle-Perales reports being a member of the Antimicrobial Steering Group at Waikato Hospital. Brendan Arnold is the clinical lead for Antimicrobial Stewardship at Southern District Health Board.
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- 2021
230. Effect of Intraoperative Dexmedetomidine on Recovery of Gastrointestinal Function After Abdominal Surgery in Older Adults: A Randomized Clinical Trial.
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Lu Y, Fang PP, Yu YQ, Cheng XQ, Feng XM, Wong GTC, Maze M, and Liu XS
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- Aged, China, Dexmedetomidine adverse effects, Digestive System Surgical Procedures methods, Digestive System Surgical Procedures statistics & numerical data, Double-Blind Method, Female, Gastrointestinal Tract physiology, Humans, Hypnotics and Sedatives adverse effects, Hypnotics and Sedatives pharmacology, Ileus etiology, Ileus prevention & control, Intraoperative Care methods, Intraoperative Care standards, Intraoperative Care statistics & numerical data, Male, Middle Aged, Postoperative Complications etiology, Postoperative Complications prevention & control, Time Factors, Dexmedetomidine pharmacology, Digestive System Surgical Procedures adverse effects, Gastrointestinal Tract drug effects
- Abstract
Importance: Postoperative ileus is common after abdominal surgery, and small clinical studies have reported that intraoperative administration of dexmedetomidine may be associated with improvements in postoperative gastrointestinal function. However, findings have been inconsistent and study samples have been small. Further examination of the effects of intraoperative dexmedetomidine on postoperative gastrointestinal function is needed., Objective: To evaluate the effects of intraoperative intravenous dexmedetomidine vs placebo on postoperative gastrointestinal function among older patients undergoing abdominal surgery., Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at the First Affiliated Hospital of Anhui Medical University in Hefei, China (lead site), and 12 other tertiary hospitals in Anhui Province, China. A total of 808 participants aged 60 years or older who were scheduled to receive abdominal surgery with an expected surgical duration of 1 to 6 hours were enrolled. The study was conducted from August 21, 2018, to December 9, 2019., Interventions: Dexmedetomidine infusion (a loading dose of 0.5 μg/kg over 15 minutes followed by a maintenance dose of 0.2 μg/kg per hour) or placebo infusion (normal saline) during surgery., Main Outcomes and Measures: The primary outcome was time to first flatus. Secondary outcomes were postoperative gastrointestinal function measured by the I-FEED (intake, feeling nauseated, emesis, physical examination, and duration of symptoms) scoring system, time to first feces, time to first oral feeding, incidence of delirium, pain scores, sleep quality, postoperative nausea and vomiting, hospital costs, and hospital length of stay., Results: Among 808 patients enrolled, 404 were randomized to receive intraoperative dexmedetomidine, and 404 were randomized to receive placebo. In total, 133 patients (60 in the dexmedetomidine group and 73 in the placebo group) were excluded because of protocol deviations, and 675 patients (344 in the dexmedetomidine group and 331 in the placebo group; mean [SD] age, 70.2 [6.1] years; 445 men [65.9%]) were included in the per-protocol analysis. The dexmedetomidine group had a significantly shorter time to first flatus (median, 65 hours [IQR, 48-78 hours] vs 78 hours [62-93 hours], respectively; P < .001), time to first feces (median, 85 hours [IQR, 68-115 hours] vs 98 hours [IQR, 74-121 hours]; P = .001), and hospital length of stay (median, 13 days [IQR, 10-17 days] vs 15 days [IQR, 11-18 days]; P = .005) than the control group. Postoperative gastrointestinal function (as measured by the I-FEED score) and delirium incidence were similar in the dexmedetomidine and control groups (eg, 248 patients [72.1%] vs 254 patients [76.7%], respectively, had I-FEED scores indicating normal postoperative gastrointestinal function; 18 patients [5.2%] vs 12 patients [3.6%] had delirium on postoperative day 3)., Conclusions and Relevance: In this randomized clinical trial, the administration of intraoperative dexmedetomidine reduced the time to first flatus, time to first feces, and length of stay after abdominal surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative recovery of gastrointestinal function among older adults., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800017232.
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- 2021
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231. Design of Clinical Trials Evaluating Sedation in Critically Ill Adults Undergoing Mechanical Ventilation: Recommendations From Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) Recommendation III.
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Ward DS, Absalom AR, Aitken LM, Balas MC, Brown DL, Burry L, Colantuoni E, Coursin D, Devlin JW, Dexter F, Dworkin RH, Egan TD, Elliott D, Egerod I, Flood P, Fraser GL, Girard TD, Gozal D, Hopkins RO, Kress J, Maze M, Needham DM, Pandharipande P, Riker R, Sessler DI, Shafer SL, Shehabi Y, Spies C, Sun LS, Tung A, and Urman RD
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- Congresses as Topic, Consensus, Delphi Technique, District of Columbia, Humans, Hypnotics and Sedatives pharmacology, Respiration, Artificial instrumentation, Respiration, Artificial methods, Time Factors, Hypnotics and Sedatives pharmacokinetics, Hypnotics and Sedatives therapeutic use
- Abstract
Objectives: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators., Design: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process., Participants: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process., Measurements and Main Results: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization., Conclusions: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials., Competing Interests: The views expressed in this article are those of the authors, none of whom have financial conflicts of interest specifically related to the issues discussed in this article. At the time of the meeting (March 28–29, 2019) on which this article is based, several participants were employed by a pharmaceutical company or had received consulting fees or honoraria from one or more pharmaceutical or device companies. Meeting participants of this article who were not employed by industry at the time of the meeting received (or their Universities received) travel stipends, hotel accommodations, and meals during the meeting from the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the Food and Drug Administration. Drs. Ward, Aitken, Colantuoni, Maze, and Needham received funding from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, and Networks (ACTTION). Dr. Ward received support for article research from the University of Rochester Maine Medical Center Spectrum Medical Partners. Dr. Absalom’s institution received funding from The Medicines Company, Carefusion (BD), and Rigel; he received support for article research from Philips, Janssen Pharma, Johnson & Johnson, Ever Pharma, Orion, and Paion. Drs. Aitken, Brown, and Coursin received funding from Innovations Consulting Group LLC. Dr. Aitken also received funding from Elsevier Australia. Dr. Balas’ institution received funding from the National Institutes of Health (NIH), the National Heart, Lung, and Blood Institute, AACN research grant; she received funding from H3C and received support for article research from the NIH. Dr. Colantuoni received support for article research from ACTTION. Dr. Dexter received funding from the Division of Management Consulting of the University of Iowa’s Department of Anesthesia. Dr. Dworkin’s institution received funding from the U.S. Food and Drug Administration (FDA); he received funding from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, AstraZeneca, Biogen, Biohaven, Boston Scientific, Braeburn, Celgene, Centrexion, Chromocell, Clexio, Collegium, Concert, Coronado, Daiichi Sankyo, Decibel, Dong-A, Editas, Eli Lilly, Eupraxia, Glenmark, Grace, Hope, Hydra, Immune, Johnson & Johnson, Lotus Clinical Research, Mainstay, Medavante, Merck, Neumentum, Neurana, NeuroBo, Novaremed, Novartis, NSGene, Olatec, Periphagen, Pfizer, Phosphagenics, Quark, Reckitt Benckiser, Regenacy, Relmada, Sanifit, Scilex, Semnur, SK Life Sciences, Sollis, Spinifex, Syntrix, Teva, Thar, Theranexus, Trevena, Vertex, and Vizuri. Dr. Girard received funding from Haisco Pharmaceutical. Dr. Hopkins’ institution received funding from Intermountain Medical and Research Foundation. Dr. Maze received funding from the University of California Office of the President and Cambridge University Press; he received support for article research from the NIH. Dr. Needham received funding from the FDA, Haisco-USA Pharmaceuticals, GlaxoSmithKline, and Novartis Pharma; he disclosed he is a principal investigator on a NIH-funded, multicentered randomized trial (R01HL132887) funded by Baxter Healthcare Corporation and Reck Medical Devices. Dr. Pandharipande’s institution received funding from Pfizer. Dr. Shehabi’s institution received funding from Orion Pharma and Pfizer; he received funding from Pfizer, Orion Pharma, Abbott Laboratories, and Ever Pharma. Dr. Sun received funding from UpToDate; she disclosed she is the Editor in Chief for UpToDate/Anesthesiology. Dr. Tung received funding from Anesthesia and Analgesia. Dr. Urman’s institution received funding from Medtronic/Covidien and AcelRx; he received funding from Merck, Sandoz, Heron, Takeda, and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)
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- 2021
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232. High-Mobility Group Box-1 and Its Potential Role in Perioperative Neurocognitive Disorders.
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Saxena S, Kruys V, De Jongh R, Vamecq J, and Maze M
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- Animals, Disease Models, Animal, HMGB1 Protein genetics, HMGB1 Protein immunology, Humans, Neurocognitive Disorders genetics, Neurocognitive Disorders immunology, Neurocognitive Disorders pathology, Perioperative Period, Protein Processing, Post-Translational, HMGB1 Protein metabolism, Neurocognitive Disorders metabolism
- Abstract
Aseptic surgical trauma provokes the release of HMGB1, which engages the innate immune response after binding to pattern-recognition receptors on circulating bone marrow-derived monocytes (BM-DM). The initial systemic inflammation, together with HMGB1, disrupts the blood-brain barrier allowing penetration of CCR2-expressing BM-DMs into the hippocampus, attracted by the chemokine MCP-1 that is upregulated by HMGB1. Within the brain parenchyma quiescent microglia are activated and, together with the translocated BM-DMs, release proinflammatory cytokines that disrupt synaptic plasticity and hence memory formation and retention, resulting in postoperative cognitive decline (PCD). Neutralizing antibodies to HMGB1 prevents the inflammatory response to trauma and PCD.
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- 2021
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233. Effect of Inhaled Xenon on Cardiac Function in Comatose Survivors of Out-of-Hospital Cardiac Arrest-A Substudy of the Xenon in Combination With Hypothermia After Cardiac Arrest Trial.
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Saraste A, Ballo H, Arola O, Laitio R, Airaksinen J, Hynninen M, Bäcklund M, Ylikoski E, Wennervirta J, Pietilä M, Roine RO, Harjola VP, Niiranen J, Korpi K, Varpula M, Scheinin H, Maze M, Vahlberg T, and Laitio T
- Abstract
This explorative substudy aimed at determining the effect of inhaled xenon on left ventricular function by echocardiography in comatose survivors of out-of-hospital cardiac arrest., Design: A randomized two-group single-blinded phase 2 clinical drug trial., Setting: A multipurpose ICU in two university hospitals., Patients: Of the 110 randomized comatose survivors after out-of-hospital cardiac arrest with a shockable rhythm in the xenon in combination with hypothermia after cardiac arrest trial, 38 patients (24-76 yr old) with complete echocardiography were included in this study., Interventions: Patients were randomized to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours or hypothermia treatment alone. Echocardiography was performed at hospital admission and 24 ± 4 hours after hypothermia., Measurements and Main Results: Left ventricular ejection fraction, myocardial longitudinal systolic strain, and diastolic function were analyzed blinded to treatment. There were 17 xenon and 21 control patients in whom echocardiography was completed. Clinical characteristics did not differ significantly between the groups. At admission, ejection fraction was similar in xenon and control patients (39% ± 10% vs 38% ± 11%; p = 0.711) but higher in xenon than control patients after hypothermia (50% ± 10% vs 42% ± 10%; p = 0.014). Global longitudinal systolic strain was similar in xenon and control patients at admission (-9.0% ± 3.8% vs -8.1% ± 3.6%; p = 0.555) but better in xenon than control patients after hypothermia (-14.4.0% ± 4.0% vs -10.5% ± 4.0%; p = 0.006). In patients with coronary artery disease, longitudinal strain improved in the nonischemic myocardial segments in xenon patients. There were no changes in diastolic function between the groups., Conclusions: Among comatose survivors of a cardiac cause out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia was associated with greater recovery of left ventricular systolic function in comparison with hypothermia alone., Competing Interests: Dr. Saraste reports grants from the Academy of Finland and Finnish Foundation for Cardiovascular Research, outside the submitted work. Dr. Airaksinen reports grants from Finnish Foundation for Cardiovascular Research, outside the submitted work. Dr. Maze is a founder, board director, and equity shareholder of NeuroproteXeon, a company that intends to commercialize the use of xenon for ongoing acute neurological injury, including its administration to successfully resuscitated patients after out-of-hospital cardiac arrest. Dr. Laitio reports consultancy fee from NeuroproteXeon Ltd., outside the submitted work. The remaining authors have disclosed that they do not have any conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)
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- 2021
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234. The Role of Microglia in Perioperative Neuroinflammation and Neurocognitive Disorders.
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Saxena S, Kruys V, Vamecq J, and Maze M
- Abstract
The aseptic trauma of peripheral surgery activates a systemic inflammatory response that results in neuro-inflammation; the microglia, the resident immunocompetent cells in the brain, are a key element of the neuroinflammatory response. In most settings microglia perform a surveillance role in the brain detecting and responding to "invaders" to maintain homeostasis. However, microglia have also been implicated in producing harm possibly by changing its phenotype from its beneficial, anti-inflammatory state (termed M2) into an injurious pro-inflammatory state (termed M1); it is likely that there are intermediates states between these polar phenotypes and some consider that a gradient exists with a number of intermediates, rather than a strict dichotomy between M1 and M2. In the pro-inflammatory phenotypes, microglia can disrupt synaptic plasticity such as long- term potentiation that can result in disorders of learning and memory of the type observed in Peri-operative Neurocognitive Disorders. Therefore, investigators have sought strategies to prevent microglia from provoking this adverse event in the perioperative period. In preclinical studies microglia can be depleted by removing trophic factors required for its maintenance; subsequent repopulation with a more beneficial microglial phenotype may result in memory enhancement, improved sensory motor function, as well as suppression of neuroinflammatory and oxidative stress pathways. Another approach consists of preventing microglial activation using the non-specific P38 MAP kinase blockers such as minocycline. Perhaps a more physiologic approach is the use of inhibitors of potassium (K
+ ) channels that are required to convert the microglia into an active state. In this context the specific K+ channels that are implicated are termed Kv1.3 and KCa3.1 and high selective inhibitors for each have been developed. Data are accumulating demonstrating the utility of these K+ channel blockers in preventing Perioperative Neurocognitive Disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Saxena, Kruys, Vamecq and Maze.)- Published
- 2021
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235. Dexmedetomidine for prevention of postoperative delirium in older adults undergoing oesophagectomy with total intravenous anaesthesia: A double-blind, randomised clinical trial.
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Hu J, Zhu M, Gao Z, Zhao S, Feng X, Chen J, Zhang Y, and Maze M
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- Aged, Anesthesia, Intravenous, Double-Blind Method, Esophagectomy adverse effects, Humans, Hypnotics and Sedatives adverse effects, Delirium epidemiology, Delirium prevention & control, Dexmedetomidine
- Abstract
Background: Dexmedetomidine is known to be a sedative. Recent studies suggest that administration of dexmedetomidine can prevent postoperative delirium (POD) which has been confirmed as a common complication after major surgery. However, its effects in patients undergoing oesophagectomy are scarce., Objective: To investigate the efficacy and safety of dexmedetomidine in reducing POD in elderly patients after transthoracic oesophagectomy with total intravenous anaesthesia (TIVA)., Design: A randomised, double-blind, placebo-controlled trial., Setting: Single-centre, tertiary care hospital, November 2016 to September 2018., Patients: Eligible patients (n = 177) undergoing transthoracic oesophagectomy were randomly assigned to receive total intravenous anaesthesia (TIVA, n = 87) or dexmedetomidine with TIVA (DEX-TIVA, n = 90)., Interventions: Patients receiving DEX-TIVA received a loading dose of dexmedetomidine (0.4 μg kg-1), over 15 min, followed by a continuous infusion at a rate of 0.1 μg kg-1 h-1 until 1 h before the end of surgery. Patients receiving TIVA received physiological saline with a similar infusion rate protocol., Outcome Measures: The primary outcome was the incidence of POD. The secondary endpoints were the incidence of emergence agitation, serum interleukin-6 (IL-6) levels and haemodynamic profile., Results: All randomised patients were included with planned intention-to-treat analyses for POD. Delirium occurred in 15 (16.7%) of 90 cases given dexmedetomidine, and in 32 (36.8%) of 87 cases given saline (P = 0.0036). The DEX-TIVA group showed less frequent emergence agitation than the TIVA group (22.1 vs. 48.0%, P = 0.0058). The incremental change in surgery-induced IL-6 levels was greater in the TIVA group than DEX-TIVA group (P < 0.0001)., Conclusion: Adding peri-operative dexmedetomidine to a total intravenous anaesthetic safely reduces POD and emergence agitation in elderly patients undergoing open transthoracic oesophagectomy. These benefits were associated with a postoperative reduction in circulating levels of the pro-inflammatory cytokine IL-6 and stabilisation of the haemodynamic profile., Trial Registration: Chinese Clinical Trials Register Identifier: ChiCTR-IPR-17010881., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology.)
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- 2021
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236. Preoperative sedentary behavior is neither a risk factor for perioperative neurocognitive disorders nor associated with an increase in peripheral inflammation, a prospective observational cohort study.
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Saxena S, Rodts C, Nuyens V, Lazaron J, Sosnowski V, Verdonk F, Seidel L, Albert A, Boogaerts J, Kruys V, Maze M, and Vamecq J
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- Aged, Belgium epidemiology, Cohort Studies, Female, Geriatric Assessment methods, Humans, Male, Middle Aged, Prospective Studies, Inflammation blood, Inflammation epidemiology, Neurocognitive Disorders blood, Neurocognitive Disorders epidemiology, Preoperative Period, Sedentary Behavior
- Abstract
Background: Surgical interventions result in a postoperative rise in circulating inflammatory cytokines and high molecular group box protein 1 (HMGB1). Herein, the impact of a sedentary lifestyle and other age-related factors on the development of perioperative neurocognitive disorders (PND) following non-cardiac surgical procedures was assessed in an older (55-75 years-old) surgical population., Methods: Prior to surgery, patients were asked questions regarding their sedentary behavior and daily habits. They also passed the Mini Mental State Examination (MMSE) and their blood circulating interleukin 6 (IL-6) and HMGB1 levels were assayed by ELISA. IL-6 and HMGB1 measurements were repeated respectively 6 and 24 h after surgery. MMSE was re-evaluated 6 weeks and whenever possible 3 months after surgery., Results: Thirty-eight patients were enrolled in the study from January until July 2019. The study identified self-sufficiency, multilinguism, and overall health score on the geriatric depression scale, as protectors against PND. No other demographic (age, sex), environmental (solitary/non-solitary housing, professional and physical activities, smoking, alcohol drinking), comorbidity (antipsychotic drug uptake, diabetic state) and type of surgery (orthopedic, general, genitourinary) influenced the development of PND. Although some factors (surgery type and age) influenced the surgery-induced rise in the circulating IL-6 levels, they did not impact HMGB1., Conclusion: Inflammaging, reflected by the greater increment of surgery-induced IL-6 in patients with advanced age, was present. As trauma-induced release of HMGB1 was not similarly affected by age, we surmise that HMGB1, rather than circulating cytokines, is the key driver of the trauma-induced inflammatory cascade leading to PND., Trial Registration: Clinicaltrials.gov identifier: NCT03805685 .
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- 2020
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237. Robert D. Sanders, B.Sc., M.B.B.S., Ph.D., F.R.C.A., Recipient of the 2020 James E. Cottrell, M.D., Presidential Scholar Award.
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Pearce RA and Maze M
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- History, 20th Century, History, 21st Century, Humans, Anesthesiology history, Awards and Prizes, Medical Laboratory Personnel history, Societies, Medical history
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- 2020
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238. Blocking Kv1.3 potassium channels prevents postoperative neuroinflammation and cognitive decline without impairing wound healing in mice.
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Lai IK, Valdearcos M, Morioka K, Saxena S, Feng X, Li R, Uchida Y, Lijun A, Li W, Pan J, Koliwad S, Marcucio R, Wulff H, and Maze M
- Subjects
- Animals, Disease Models, Animal, Mice, Cognitive Dysfunction prevention & control, Encephalitis prevention & control, Kv1.3 Potassium Channel antagonists & inhibitors, Postoperative Complications prevention & control, Wound Healing physiology
- Abstract
Background: Postoperative cognitive decline (PCD) requires microglial activation. Voltage-gated Kv1.3 potassium channels are involved in microglial activation. We determined the role of Kv1.3 in PCD and the efficacy and safety of inhibiting Kv1.3 with phenoxyalkoxypsoralen-1 (PAP-1) in preventing PCD in a mouse model., Methods: After institutional approval, we assessed whether Kv1.3-deficient mice (Kv1.3
-/- ) exhibited PCD, evidenced by tibial-fracture surgery-induced decline in aversive freezing behaviour, and whether PAP-1 could prevent PCD and postoperative neuroinflammation in PCD-vulnerable diet-induced obese (DIO) mice. We also evaluated whether PAP-1 altered either postoperative peripheral inflammation or tibial-fracture healing., Results: Freezing behaviour was unaltered in postoperative Kv1.3-/- mice. In DIO mice, PAP-1 prevented postoperative (i) attenuation of freezing behaviour (54 [17.3]% vs 33.4 [12.7]%; P=0.03), (ii) hippocampal microglial activation by size (130 [31] pixels vs 249 [49]; P<0.001) and fluorescence intensity (12 000 [2260] vs 20 800 [5080] absorbance units; P<0.001), and (iii) hippocampal upregulation of interleukin-6 (IL-6) (14.9 [5.7] vs 25.6 [10.4] pg mg-1 ; P=0.011). Phenoxyalkoxypsoralen-1 neither affected surgery-induced upregulation of plasma IL-6 nor cartilage and bone components of the surgical fracture callus., Conclusions: Microglial-mediated PCD requires Kv1.3 activity, determined by genetic and pharmacological targeting approaches. Phenoxyalkoxypsoralen-1 blockade of Kv1.3 prevented surgery-induced hippocampal microglial activation and neuroinflammation in mice known to be vulnerable to PCD. Regarding perioperative safety, these beneficial effects of PAP-1 treatment occurred without impacting fracture healing. Kv1.3 blockers, currently undergoing clinical trials for other conditions, may represent an effective and safe intervention to prevent PCD., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)- Published
- 2020
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239. Programmable Digital Liquid Metal Droplets in Reconfigurable Magnetic Fields.
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Li X, Li S, Lu Y, Liu M, Li F, Yang H, Tang SY, Zhang S, Li W, and Sun L
- Abstract
Gallium-based liquid metals exhibit excellent locomotion and deformation capabilities under external stimuli and has potential in developing intelligent robots. Programing the locomotion and morphology of the Liquid metal (LM) to endow it with functionalities and intelligence as robots is charming but remains challenging. In this study, we develop a programmable digital LM (PDLM) control platform that can realize versatile locomotion and morphological manipulation of magnetic LM (MLM) droplets using arrays of electromagnets. We demonstrate on-demand transportation, deformation, breakup, and merging of multiple MLM droplets simultaneously and precisely. We find that the intriguing behaviors of MLM under a magnetic field are due to the interplay of surface tension and magnetic forces. Furthermore, we present a functional cooperative droplet robot by equipping the MLM droplets with three-dimensionally printed microtool modules. We show that both the position and orientation of a rod-shaped object can be precisely manipulated by the cooperation of the MLM droplet robots. More interestingly, we explore the capability of the MLM droplet robots for cooperatively handling a copper wire to connect and disconnect electronic circuits. Finally, we demonstrate that the PDLM control platform is capable of programing a group of MLM droplets to accomplish a digital display task. We believe that the PDLM control system presents a promising potential in developing LM-based reconfigurable circuits, digital display systems, and biomimetic soft robotic systems with high controllability, multifunctionalities, and intelligence.
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- 2020
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240. Dexmedetomidine Exerts an Anti-inflammatory Effect via α2 Adrenoceptors to Prevent Lipopolysaccharide-induced Cognitive Decline in Mice.
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Li R, Lai IK, Pan JZ, Zhang P, and Maze M
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- Animals, Anti-Inflammatory Agents, Critical Illness, Lipopolysaccharides, Male, Mice, Receptors, Adrenergic, Rodentia, Tumor Necrosis Factor-alpha, Cognitive Dysfunction, Dexmedetomidine
- Abstract
Background: Clinical studies have shown that dexmedetomidine ameliorates cognitive decline in both the postoperative and critical care settings. This study determined the mechanism(s) for the benefit provided by dexmedetomidine in a medical illness in mice induced by lipopolysaccharide., Methods: Cognitive decline, peripheral and hippocampal inflammation, blood-brain barrier permeability, and inflammation resolution were assessed in male mice. Dexmedetomidine was administered in the presence of lipopolysaccharide and in combination with blockers. Cultured macrophages (RAW 264.7; BV-2) were exposed to lipopolysaccharide ± dexmedetomidine ± yohimbine; tumor necrosis factor α release into the medium and monocyte NFκB activity was determined., Results: In vivo, lipopolysaccharide-induced cognitive decline and inflammation (mean ± SD) were reversed by dexmedetomidine (freezing time, 55.68 ± 12.31 vs. 35.40 ± 17.66%, P = 0.0286, n = 14; plasma interleukin [IL]-1β: 30.53 ± 9.53 vs. 75.68 ± 11.04 pg/ml, P < 0.0001; hippocampal IL-1β: 3.66 ± 1.88 vs. 28.73 ± 5.20 pg/mg, P < 0.0001; n = 8), which was prevented by α2 adrenoceptor antagonists. Similar results were found in 12-month-old mice. Lipopolysaccharide also increased blood-brain barrier leakage, inflammation-resolution orchestrator, and proresolving and proinflammatory mediators; each lipopolysaccharide effect was attenuated by dexmedetomidine, and yohimbine prevented dexmedetomidine's attenuating effect. In vitro, lipopolysaccharide-induced tumor necrosis factor α release (RAW 264.7: 6,308.00 ± 213.60 vs. 7,767.00 ± 358.10 pg/ml, P < 0.0001; BV-2: 1,075.00 ± 40.41 vs. 1,280.00 ± 100.30 pg/ml, P = 0.0003) and NFκB-p65 activity (nuclear translocation [RAW 264.7: 1.23 ± 0.31 vs. 2.36 ± 0.23, P = 0.0031; BV-2: 1.08 ± 0.26 vs. 1.78 ± 0.14, P = 0.0116]; phosphorylation [RAW 264.7: 1.22 ± 0.40 vs. 1.94 ± 0.23, P = 0.0493; BV-2: 1.04 ± 0.36 vs. 2.04 ± 0.17, P = 0.0025]) were reversed by dexmedetomidine, which was prevented by yohimbine., Conclusions: Preclinical studies suggest that the cognitive benefit provided by dexmedetomidine in mice administered lipopolysaccharide is mediated through α2 adrenoceptor-mediated anti-inflammatory pathways.
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- 2020
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241. Towards elimination of tuberculosis in New Zealand.
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Verrall AJ, Hill PC, Thorburn D, Maze M, Perumal L, Grimwade K, Thornley CN, Freeman J, Nisbet M, and Blackmore TK
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- Humans, Mass Screening, Native Hawaiian or Other Pacific Islander, New Zealand, Public Health, Public Health Surveillance, Tuberculosis epidemiology, Tuberculosis transmission, Disease Eradication, Tuberculosis prevention & control
- Abstract
New Zealand could be the first country in the world to eliminate tuberculosis (TB). We propose a TB elimination strategy based on the eight-point World Health Organization (WHO) action framework for low incidence countries. Priority actions recommended by the WHO include 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) identify active TB and undertake screening for latent tuberculosis infection (LTBI) in recent TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. In New Zealand, central government needs to take greater responsibility for TB policy and programme governance. Urgent action is required to prevent TB in higher risk groups including Māori communities, and to enable immigration screening to detect and treat LTBI. Clinical services need to be supported to implement new guidelines for LTBI that enable better targeting of screening and shorter, safer treatment regimens. Access to WHO recommended treatment regimens needs to be guaranteed for drug-resistant TB. Better use of existing data could better define priority areas for action and assist in the evaluation of current control activities. Access to GeneXpert® MTB-RIF near the point of care and whole genome sequencing nationally would greatly improve clinical and public health management through early identification of drug resistance and outbreaks. New Zealand already has a world-class TB research community that could be better deployed to assist high-incidence countries through research and training., Competing Interests: Dr Perumal reports and works as the local Medical Officer of Health for TB control in the Auckland Region.
- Published
- 2020
242. Politicians: please work together to minimise the spread of COVID-19.
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Murdoch D, Addidle M, Andersson HS, Arnold B, Balm M, Benschop J, Betty B, Birch M, Bloomfield M, Brunton C, Burns A, Chambers S, Cook L, Dalton S, Duncan H, Elvy J, Everts R, Freeman J, French N, Grimwade K, Hammer D, Hayman D, Holland D, Hudson B, Huggan P, Ikram R, Jack S, Kelly M, Lamont I, Maze M, McAuliffe G, McBride S, Metcalf S, Morpeth S, Morris A, Murton S, Pink R, Pithie A, Pitout M, Priest P, Raymond N, Read K, Ritchie S, Rogers M, Schroeder P, Taylor S, Taylor J, Thomas M, Upton A, Ussher J, Werno A, and Wiles S
- Subjects
- COVID-19, Civil Defense, Communication, Health Personnel, Humans, New Zealand, Coronavirus Infections epidemiology, Coronavirus Infections prevention & control, Coronavirus Infections transmission, Evidence-Based Medicine, Interprofessional Relations, Leadership, Pneumonia, Viral epidemiology, Pneumonia, Viral prevention & control, Pneumonia, Viral transmission, Politics
- Abstract
Competing Interests: Nil.
- Published
- 2020
243. Neuroprotective Properties of Xenon.
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Maze M and Laitio T
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- Anesthetics, Inhalation pharmacology, Animals, Coma drug therapy, Humans, Neuroprotection drug effects, Neuroprotective Agents pharmacology, Neurotoxicity Syndromes drug therapy, Xenon pharmacology
- Abstract
Xenon is a rare noble gas that was introduced into clinical practice more than 70 years ago. Xenon's clinical properties are predicated by its ability to fit into preformed cavities of macromolecules thereby altering their biological functions. One such action targets the NMDA-subtype of the glutamate receptors thereby inhibiting its excitatory action. As the glutamate receptors are pivotal for both anesthesia and acute neurological injury, its clinical use has included both general anesthesia as well as neuroprotection. In this manuscript, the efficacy and safety of xenon in clinical trials that address both the anesthetic and neuroprotective applications are discussed. Because of the clinical safety of this chemically inert monatomic gas, the lack of an alternative for neuroprotection, and encouraging phase 2 trial data, a multinational pivotal randomized clinical trial (XePOHCAS) has been launched to assess the utility of xenon for patients that have been successfully resuscitated following an out of hospital cardiac arrest but still remain comatose, indicating ongoing neurological ischemic-perfusion injury. If successful, the trial will herald a new era of treatments for previously intractable conditions such as traumatic brain injury, ischemic and hemorrhagic strokes, and anesthetic-induced developmental neurotoxicity.
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- 2020
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244. Perioperative Neurocognitive Disorder: State of the Preclinical Science.
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Eckenhoff RG, Maze M, Xie Z, Culley DJ, Goodlin SJ, Zuo Z, Wei H, Whittington RA, Terrando N, Orser BA, and Eckenhoff MF
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- Animals, Disease Models, Animal, Neurocognitive Disorders prevention & control, Postoperative Complications prevention & control, Neurocognitive Disorders physiopathology, Neurocognitive Disorders therapy, Perioperative Period, Postoperative Complications physiopathology, Postoperative Complications therapy, Research Design
- Abstract
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.
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- 2020
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245. Dexmedetomidine modulates neuroinflammation and improves outcome via alpha2-adrenergic receptor signaling after rat spinal cord injury.
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Gao J, Sun Z, Xiao Z, Du Q, Niu X, Wang G, Chang YW, Sun Y, Sun W, Lin A, Bresnahan JC, Maze M, Beattie MS, and Pan JZ
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- Animals, Cells, Cultured, Disease Models, Animal, Female, Microglia drug effects, Rats, Rats, Long-Evans, Signal Transduction drug effects, Spinal Cord drug effects, Spinal Cord physiopathology, Adrenergic alpha-2 Receptor Agonists pharmacology, Dexmedetomidine pharmacology, Inflammation drug therapy, Receptors, Adrenergic, alpha-2 drug effects, Spinal Cord Injuries drug therapy, Spinal Cord Injuries physiopathology
- Abstract
Background: Spinal cord injury induces inflammatory responses that include the release of cytokines and the recruitment and activation of macrophages and microglia. Neuroinflammation at the lesion site contributes to secondary tissue injury and permanent locomotor dysfunction. Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is anti-inflammatory and neuroprotective in both preclinical and clinical trials. We investigated the effect of DEX on the microglial response, and histological and neurological outcomes in a rat model of cervical spinal cord injury., Methods: Anaesthetised rats underwent unilateral (right) C5 spinal cord contusion (75 kdyne) using an impactor device. The locomotor function, injury size, and inflammatory responses were assessed. The effect of DEX was also studied in a microglial cell culture model., Results: DEX significantly improved the ipsilateral upper-limb motor dysfunction (grooming and paw placement; P<0.0001 and P=0.0012), decreased the injury size (P<0.05), spared white matter (P<0.05), and reduced the number of activated macrophages (P<0.05) at the injury site 4 weeks post-SCI. In DEX-treated rats after injury, tissue RNA expression indicated a significant downregulation of pro-inflammatory markers (e.g. interleukin [IL]-1β, tumour necrosis factor-α, interleukin (IL)-6, and CD11b) and an upregulation of anti-inflammatory and pro-resolving M2 responses (e.g. IL-4, arginase-1, and CD206) (P<0.05). In lipopolysaccharide-stimulated cultured microglia, DEX produced a similar inflammation-modulatory effect as was seen in spinal cord injury. The benefits of DEX on these outcomes were mostly reversed by an α2-adrenergic receptor antagonist., Conclusions: DEX significantly improves neurological outcomes and decreases tissue damage after spinal cord injury, which is associated with modulation of neuroinflammation and is partially mediated via α2-adrenergic receptor signaling., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
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246. Impact of Dexmedetomidine on Long-term Outcomes After Noncardiac Surgery in Elderly: 3-Year Follow-up of a Randomized Controlled Trial.
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Zhang DF, Su X, Meng ZT, Li HL, Wang DX, Xue-Ying Li, Maze M, and Ma D
- Subjects
- Aged, Analgesics, Non-Narcotic administration & dosage, Cognition physiology, Delirium etiology, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Infusions, Intravenous, Male, Pain, Postoperative complications, Retrospective Studies, Time Factors, Treatment Outcome, Delirium prevention & control, Dexmedetomidine administration & dosage, Pain, Postoperative drug therapy, Postoperative Care methods, Quality of Life, Surgical Procedures, Operative
- Abstract
Objectives: The aim was to compare the long-term outcomes of low-dose dexmedetomidine versus placebo in a randomized controlled trial (ChiCTR-TRC-10000802)., Background: Low-dose dexmedetomidine infusion decreased delirium occurrence within 1 week after surgery in elderly admitted to the intensive care unit (ICU) after noncardiac surgery, but the long-term outcome of this intervention is unknown., Methods: Patients or their family members were telephone-interviewed for a 3-year follow-up data collection of survival, cognitive function assessed with the modified Telephone Interview for Cognitive Status, and quality of life evaluated with the World Health Organization Quality of Life., Results: Of the 700 patients, 23 (3.3%) were lost at 3-year follow-up. The 3-year overall survival was not statistically different between the dexmedetomidine and placebo groups [114 deaths vs 122/350; hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.68-1.13, P = 0.303]. The survival rates at 6 months, 1 year, and 2 years were significantly higher in the dexmedetomidine than in the placebo group (rate difference of 5.2%, 5.3%, and 6.7% respectively; all P < 0.05). The remaining 98.4% (434/441) 3-year survivors, the dexmedetomidine group, had significantly better cognitive function (mean difference 4.7, 95% CI 3.8-5.6, P < 0.0001) and quality of life (physical domain: 13.6 [10.6-16.6]; psychological domain: 15.2 [12.5-18.0]; social relationship domain: 8.1 [5.5-10.7]; environment domain: 13.3 [10.9-15.7]; all P < 0.0001) than in the placebo group., Conclusions: For elderly admitted to ICU after noncardiac surgery, low-dose dexmedetomidine infusion did not significantly change 3-year overall survival, but increased survival up to 2 years, and improved cognitive function and quality of life in 3-year survivors.
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- 2019
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247. Neuroinflammation is a putative target for the prevention and treatment of perioperative neurocognitive disorders.
- Author
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Saxena S, Lai IK, Li R, and Maze M
- Subjects
- Aging immunology, Humans, Inflammation immunology, Inflammation prevention & control, Neurocognitive Disorders immunology, Neurocognitive Disorders physiopathology, Risk Factors, Wound Healing immunology, Inflammation drug therapy, Inflammation physiopathology, Neurocognitive Disorders drug therapy, Neurocognitive Disorders prevention & control, Perioperative Care
- Abstract
Introduction: The demographics of aging of the surgical population has increased the risk for perioperative neurocognitive disorders in which trauma-induced neuroinflammation plays a pivotal role., Sources of Data: After determining the scope of the review, the authors used PubMed with select phrases encompassing the words in the scope. Both preclinical and clinical reports were considered., Areas of Agreement: Neuroinflammation is a sine qua non for development of perioperative neurocognitive disorders., Areas of Controversy: What is the best method for ameliorating trauma-induced neuroinflammation while preserving inflammation-based wound healing., Growing Points: This review considers how to prepare for and manage the vulnerable elderly surgical patient through the entire spectrum, from preoperative assessment to postoperative period., Areas Timely for Developing Research: What are the most effective and safest interventions for preventing and/or reversing Perioperative Neurocognitive Disorders., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2019
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248. Diagnostic accuracy of leptospirosis whole-cell lateral flow assays: a systematic review and meta-analysis.
- Author
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Maze MJ, Sharples KJ, Allan KJ, Rubach MP, and Crump JA
- Subjects
- Humans, Point-of-Care Systems, Sensitivity and Specificity, Antigens, Bacterial immunology, Bacterial Proteins immunology, Biological Assay methods, Immunoassay methods, Leptospira immunology, Leptospirosis diagnosis
- Abstract
Background: Leptospirosis is under-diagnosed by clinicians in many high-incidence countries, because reference diagnostic tests are largely unavailable. Lateral flow assays (LFA) that use antigen derived from heat-treated whole cell Leptospira biflexa serovar Patoc have the potential to improve leptospirosis diagnosis in resource-limited settings., Objectives: We sought to summarize estimates of sensitivity and specificity of LFA by conducting a systematic review and meta-analysis of evaluations of the accuracy of LFA to diagnose human leptospirosis., Data Sources: On 4 July 2017 we searched three medical databases. Study eligibility criteriaArticles were included if they were a study of LFA sensitivity and specificity., Participants: Patients with suspected leptospirosis., Interventions: Nil., Methods: For included articles, we assessed study quality, characteristics of participants and diagnostic testing methods. We estimated sensitivity and specificity for each study against the study-defined case definition as the reference standard, and performed a meta-analysis using a random-effects bivariate model., Results: Our search identified 225 unique reports, of which we included nine (4%) published reports containing 11 studies. We classified one (9%) study as high quality. Nine (82%) studies used reference tests with considerable risk of misclassification. Our pooled estimates of sensitivity and specificity were 79% (95% CI 70%-86%) and 92% (95% CI 85%-96%), respectively., Conclusions: As the evidence base for determining the accuracy of LFA is small and at risk of bias, pooled estimates of sensitivity and specificity should be interpreted with caution. Further studies should use either reference tests with high sensitivity and specificity or statistical techniques that account for an imperfect reference standard., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2019
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249. Specialised pro-resolving mediators: the magic bullet for perioperative neurocognitive disorders?
- Author
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Li R, Lai IK, and Maze M
- Subjects
- Animals, Humans, Inflammation Mediators therapeutic use, Neurocognitive Disorders prevention & control, Perioperative Care methods, Postoperative Complications prevention & control
- Published
- 2019
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250. Tp-e interval and Tp-e/QT ratio in clinically stable pediatric heart transplant recipients.
- Author
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Koca S, Paç FA, Kocabeyoğlu S, Zabun M, Eriş D, Sert DE, Kervan Ü, and Paç M
- Subjects
- Adolescent, Case-Control Studies, Child, Electrocardiography, Female, Heart Conduction System, Heart Defects, Congenital surgery, Humans, Male, Arrhythmias, Cardiac physiopathology, Heart Transplantation
- Abstract
Objective: A study of the T wave peak-to-end (Tp-e) interval, the Tp-e/QT ratio, and the Tp-e/QTc ratio in pediatric heart transplant recipients (HTRs), a group which has a higher risk of sudden cardiac death than the normal population, has not previously been reported. The aim of this study was to assess alterations in ventricular repolarization using the Tp-e interval, Tp-e/ QT ratio, and Tp-e/QTc ratio in clinically stable pediatric HTRs., Methods: A total of 13 clinically stable HTRs, 13 patients who had undergone cardiac surgery (CS) under cardiopulmonary bypass, and 16 healthy controls under 18 years of age were retrospectively evaluated., Results: No significant differences were observed between the HTR, CS, and control groups in terms of QTc, JTc interval, and T wave amplitude (p>0.05). The Tp-e interval (p=0.001), Tp-e/QT ratio (p<0.001), and Tp-e/QTc ratio (p=0.001) were significantly higher in the HTR group compared with the CS and normal control participants., Conclusion: The Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were elevated in stable HTRs compared with the normal and CS groups.
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- 2019
- Full Text
- View/download PDF
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