Publications by authors named "Robert D Sanders"

Objective: Early detection of hypoxic-ischemic encephalopathy (HIE) in neonates is critical. We conducted a pilot cohort study to determine the feasibility of collecting umbilical cord blood samples for neurofilament light (NfL) and to assess the association of NfL with non-reassuring fetal status and other cord biomarkers. We aimed to address (1) Feasibility of cord NfL sample collection and analysis; (2) Association of NfL with non-reassuring fetal status (CTG changes and/or documented non-reassuring fetal status), neonatal intensive care unit (NICU) admission and length of stay; (3) Correlation of NfL with other cord biomarkers.

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Tau phosphorylation plays an important role in brain physiology and pathology. During foetal development, it supports microtubule dynamics and neuroplasticity, whereas in Alzheimer's disease (AD), it drives pathological tau aggregation and tangle formation. In this multicentre study ( = 462), we measured plasma phosphorylated-tau217 in healthy newborns, premature infants, patients with AD and healthy controls across various age groups.

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Introduction: Dexmedetomidine is a selective α-adrenergic agonist used as an anesthesia adjunct to produce a state of sleep-like sedation. However, how brain activity compares quantitatively during dexmedetomidine anesthesia to that during natural sleep, and thus just how "sleep-like" dexmedetomidine anesthesia is, remains unclear. Previously, we showed that the general anesthetic propofol is associated with changes in connectivity and cortical network structure comparable to those observed during sleep.

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Background: Several methods are used to measure delirium severity in the postoperative period. Here, we compare severity scores from two common assessment methods: the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM) and the Delirium Rating Scale-Revised-98 (DRS).

Methods: Data were collected as part of an ongoing observational cohort study of perioperative delirium in patients >65 yr old undergoing major elective surgery with an anticipated hospital stay of at least 2 days.

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Background: Dexmedetomidine is seen as a promising agent for the prevention of postoperative delirium after cardiac surgery, but the largest study (DECADE) paradoxically suggested an increased risk of delirium.

Methods: Studies were selected using inclusion/exclusion criteria after conducting online database searches for randomised controlled trials. The primary outcome was the incidence of postoperative delirium with a minimum clinically important difference (MCID), defined as an odds ratio >1.

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Background: Postoperative delirium may be mediated by systemic inflammation and neuroinflammation. By inhibiting the proinflammatory actions of plasmin, tranexamic acid (TXA) may decrease postoperative delirium. To explore this hypothesis, we modified an ongoing randomised trial of TXA on blood loss, adding measures of delirium, cognition, systemic inflammation, and astrocyte activation.

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Objective: Current methods for early detection of hypoxic-ischemic encephalopathy (HIE) are limited by lack of specificity, cost, and time constraints. Blood tau protein concentrations reflect neuropathology in adults. This study examines tau as a potential HIE biomarker in neonates by relating cord blood levels to short-term fetomaternal outcomes.

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Objective: Early detection of hypoxic-ischaemic encephalopathy (HIE) in neonates is critical. We conducted a pilot cohort study to determine the feasibility of collecting umbilical cord blood samples for neurofilament light (NfL) and to assess the association of NfL with non-reassuring fetal status and other cord biomarkers.

Design: Prospective cohort study.

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Postoperative neurocognitive disorders (PNDs) are frequent and serious perioperative complications in the elderly, and are associated with increased morbidity and mortality, length of hospital stay, and need for long-term care. At present, the pathogenesis of PND is not completely clear, and there are various risk factors including surgical trauma and stress mediating systemic inflammation towards neuroinflammation development which causes brain structural and functional changes namely PND. For elderly patients, perioperative neurological monitoring may provide insights into brain function status.

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Perioperative neuronal injury includes both delirium and postoperative cognitive decline, and has profound potentially long-term effects on surgical patients and an economic cost. Recent advances have been made in the underlying biological causes of these injuries, including validation of biomarkers of neuronal damage such as neurofilament light, further understanding of the inflammatory pathways and mediators responsible for neuronal injuries, metabolic triggers, and the role of ischaemia. Several novel approaches to perioperative protection of brain health are also being trialled.

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Objectives: (1) Gain insight into the mechanisms of postoperative delirium (POD). (2) Determine mechanistic overlap with post-ictal delirium (PID). Epilepsy patients undergoing intracranial electrophysiological monitoring can experience both POD and PID, and thus are suitable subjects for these investigations.

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Background: Intraoperative awareness, without explicit recall, occurs after induction of anaesthesia in approximately 10% of persons under 40 yr of age. Most anaesthetic agents minimally suppress the noradrenergic system. We hypothesised that addition of dexmedetomidine, which suppresses noradrenergic activity, may reduce encephalographic (EEG) arousal in response to tracheal intubation; such an effect would lay the foundation for future studies of dexmedetomidine in reducing intraoperative awareness.

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Background: The ability of current depth-of-anaesthesia monitors to differentiate subtle changes in the conscious state has not been well characterised. We examine the variability in bispectral index (BIS) scores associated with disconnected conscious and unconscious states as confirmed by a novel serial awakening paradigm.

Methods: Seventy adult participants, given propofol or dexmedetomidine, had a cumulative 1381 electroencephalographic (EEG) recordings across two centres.

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Background: Postoperative delirium may be mediated by perioperative systemic- and neuro-inflammation. By inhibiting the pro-inflammatory actions of plasmin, tranexamic acid (TXA) may decrease postoperative delirium. To explore this hypothesis, we modified an ongoing randomised trial of TXA, adding measures of postoperative delirium, cognitive function, systemic cytokines, and astrocyte activation.

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Background: We aimed to assess perioperative changes in fibrinogen in the cerebrospinal fluid (CSF), their association with markers of blood-brain barrier breakdown and neuroinflammation, and their association with postoperative delirium severity.

Methods: We conducted a secondary analysis of the Interventions for Postoperative Delirium-Biomarker 2 (IPOD-B2, NCT02926417) study, a prospective observational cohort study. We included 24 patients aged >21 yr undergoing aortic aneurysm repair.

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Background: Delaying surgery after a major cardiovascular event might reduce adverse postoperative outcomes. The time interval represents a potentially modifiable risk factor but is not well studied.

Methods: This was a longitudinal retrospective population-based cohort study, linking data from Hospital Episode Statistics for NHS England and the Myocardial Ischaemia National Audit Project.

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Background: Previous studies have shown that major surgical and medical hospital admissions are associated with cognitive decline in older people (aged 40-69 years at recruitment), which is concerning for patients and caregivers. We aimed to validate these findings in a large cohort and investigate associations with neurodegeneration using MRI.

Methods: For this population-based study, we analysed data from the UK Biobank collected from March 13, 2006, to July 16, 2023, linked to the National Health Service Hospital Episode Statistics database, excluding participants with dementia diagnoses.

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In an era of 'big data', we propose that a collaborative network approach will drive a better understanding of the mechanisms of delirium, and more rapid development of therapies. We have formed the International Delirium Pathophysiology & Electrophysiology Network for Data sharing (iDEPEND) group with a key aim to 'facilitate the study of delirium pathogenesis with electrophysiology, imaging, and biomarkers including data acquisition, analysis, and interpretation'. Our initial focus is on studies of electrophysiology as we anticipate this methodology has great potential to enhance our understanding of delirium.

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Background: Whilst both mental illness comorbidity and the delivery of emergency surgery are commonplace in Australia, there is little evidence investigating any link between them. As such, this study examines the emergency surgical outcomes for patients with mental illness compared to other surgical patients within the Australian public surgical system.

Methods: Retrospective cohort study involving adult emergency and elective surgical patients treated at three public hospitals in Sydney, Australia between 2018 and 2019.

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Background: Disconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world.

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Background: Human consciousness is generally thought to emerge from the activity of intrinsic connectivity networks (resting-state networks [RSNs]) of the brain, which have topological characteristics including, among others, graph strength and efficiency. So far, most functional brain imaging studies in anesthetized subjects have compared wakefulness and unresponsiveness, a state considered as corresponding to unconsciousness. Sedation and general anesthesia not only produce unconsciousness but also phenomenological states of preserved mental content and perception of the environment (connected consciousness), and preserved mental content but no perception of the environment (disconnected consciousness).

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