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It is unknown if the type of general anaesthetic used for maintenance of anaesthesia affects the incidence of postoperative cognitive dysfunction (POCD). The aim of this study was to compare the incidence of POCD in patients administered either sevoflurane or propofol for maintenance of anaesthesia during total hip replacement surgery. Following administration of a spinal anaesthetic, patients received either sevoflurane (n=121) or propofol (n=171) at the discretion of the anaesthetist for maintenance of general anaesthesia to maintain the processed electroencephalogram (bispectral index, BIS) under 60. POCD was assessed postoperatively at day 7, three months, and 12 months using a neurocognitive test battery. There was no statistically significant difference between the incidence of POCD at any timepoint with sevoflurane compared to propofol. The mean BIS was significantly lower in the sevoflurane group than in the propofol group (mean BIS 44.3 [standard deviation, SD, 7.5] in the sevoflurane group versus 53.7 [SD 8.1] in the propofol group, P=0.0001). However, there was no statistically significant association between intraoperative BIS level and the incidence of POCD at any timepoint. Our results suggest that the incidence of POCD is not strongly influenced by the type of anaesthesia used in elderly patients.

Background Postoperative delirium (POD) is a serious complication of surgery associated with prolonged hospitalisation, long‐term cognitive decline, dementia and mortality. There is increasing evidence that electroencephalography (EEG) monitoring may reduce the incidence of POD, however, the best method for achieving this is unclear. Method This presentation will present the results of a multicentre randomised clinical trial of 515 at‐risk patients undergoing major surgery from 8 centres in 3 countries who were assessed for POD for 5 days postoperatively. They also underwent cognitive screening at baseline, discharge, 30 days and one year postoperatively. Patients were assigned to light or deep anaesthesia. Additionally, this presentation will consider a meta‐analysis of available studies investigating EEG monitoring to prevent delirium and outline the importance of EEG spectrogram interpretation as part of EEG monitoring and consequent anesthetic titration when using this technique to reduce or prevent POD. Result The incidence of POD was lower (19%) in the light anesthesia group compared with the deep anesthesia group (28%) (OR 0.58 (95% CI 0.38 to 0.88), P=0.010). Meta‐analysis results were fragile and depended on inclusion criteria of studies. Interpretation of EEG spectrograms is a developing field, but adds significant, critical information. Conclusion EEG monitoring is a possible method for preventing POD and long‐term complications. EEG spectrogram interpretation will likely add critical information to enhance this technique.

BACKGROUND Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long‐term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium‐spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. Highlights Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.

General anesthesia has been administered for over 150 years, and in that time, has become progressively safer. Improvements in outcomes have been driven by multiple advances, including the use of non-invasive monitors to assess cardiovascular and respiratory status. More recent advances have included the development and use of monitors to measure neurologic status by means of \"processed\" electroencephalography (pEEG), wherein the frontal EEG signal is analyzed by proprietary algorithms to produce a dimensionless number (scaled from 0 to 100), wherein low values are associated with deepening levels of sedation that progresses to loss of consciousness. Such monitors have been shown to enable anesthetic titration so as to expedite emergence and early recovery, and their use is advocated for the prevention of intraoperative awareness in the setting of administration of total intravenous anesthesia and neuromuscular blockade. Whether their use can minimize, or prevent, longer term adverse events is a matter of debate. In this narrative review of the most recent literature, we provide an assessment on the use of pEEG monitors in the prevention of a notable, and important, postoperative adverse outcome - delirium - in elderly patients. As we will discuss, the existing data do not support its routine use for the prevention of postoperative delirium in this, or any other, patient population.

ObjectiveTo measure cognition in patients before and after coronary angiography.DesignProspective observational cohort study.SettingUniversity teaching hospital.Patients56 patients presenting for elective coronary angiography.Main outcome measuresComputerised cognitive test battery administered before coronary angiography, before discharge from hospital and 7 days after discharge. A matched healthy control group was used as a comparator.ResultsWhen analysed by group, coronary angiography patients performed worse than matched controls at each time point. When the cognitive change was examined for each individual, of the 48 patients tested at discharge, 19 (39.6%) were classified as having a new cognitive dysfunction, and of 49 patients tested at day 7, six (12.2%) were classified as having a new cognitive dysfunction.ConclusionsThe results confirm that cognitive function is decreased in patients who have cardiovascular disease. Furthermore, coronary angiography may exacerbate this impaired cognition in some patients.

Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted in a significant reduction in atherosclerosis burden in conventionally raised (ConvR) Apolipoprotein E ( ApoE ) knockout (KO) mice but not in germ-free (GF) ApoE KO mice. Metabolomic analysis revealed that consumption of quercetin significantly increased plasma levels of benzoylglutamic acid, 3,4 dihydroxybenzoic acid (3,4-DHBA) and its sulfate-conjugated form in ConvR mice, but not in GF mice supplemented with the flavonoid. Levels of these metabolites were negatively associated with atherosclerosis burden. Furthermore, we show that 3,4-DHBA prevented lipopolysaccharide (LPS)-induced decrease in transendothelial electrical resistance (TEER). These results suggest that the effects of quercetin on atherosclerosis are influenced by gut microbes and are potentially mediated by bacterial metabolites derived from the flavonoid.

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

General anesthesia and surgery are associated with an increase in neural injury biomarkers. Elevations of these neural injury biomarkers in the perioperative period are associated with postoperative delirium. Xenon has been shown to be protective against a range of neurological insults in animal models. It remains to be seen if xenon anesthesia is neuroprotective in the perioperative setting in humans. Twenty-four participants scheduled for lithotripsy were randomized to receive either xenon or sevoflurane general anesthesia. There was no statistically significant difference in the concentrations of postoperative neural injury biomarkers between the xenon and sevoflurane group. Following the procedure there was a significant increase in the concentration from baseline of all three biomarkers at 1 hour post-induction with a return to baseline at 5 hours. General anesthesia for lithotripsy was associated with a significant increase at 1 hour post-induction in the neural injury biomarkers total tau, neurofilament light and tau phosphorylated at threonine 181, a marker of tau phosphorylation. The protocol was approved by the St. Vincent's Hospital Melbourne Ethics Committee (approval No. HREC/18/SVHM/221) on July 20, 2018 and was registered with the Australia New Zealand Clinical Trials Registry (registration No. ACTRN12618000916246) on May 31, 2018.

Background Chronic post-surgical pain (CPSP) is recognised as one of the most common and debilitating complications of major surgery. Progression from acute to chronic pain after surgery involves sensitisation of central nervous system pathways with the N-methyl-D-aspartate (NMDA) receptor having a central role. Ketamine is a potent, non-selective NMDA antagonist commonly used for management of acute postoperative pain. Inconsistent but largely supportive evidence from small trials of a preventative effect of perioperative ketamine on CPSP risk suggests that a confirmative large trial is needed. Methods The ROCKet ( R eduction O f C hronic Post-surgical Pain with Ket amine) Trial is a multicentre, double-blind, placebo-controlled, individually randomised superiority trial conducted in 36 hospitals across Australia, New Zealand, and Hong Kong. The trial aims to recruit 4884 patients undergoing abdominal, thoracic, or major orthopaedic surgery. Eligible participants are randomised equally to perioperative intravenous ketamine or placebo for up to 72 h. Incidence of pain in the area of the index surgery is measured by structured telephone interview at 3 months (primary trial endpoint) and 12 months. Pain severity, nature, and associated psychological and quality of life indices are measured using the modified Brief Pain Inventory short form, Neuropathic Pain Questionnaire, Kessler K-10 Psychological Distress Scale, Pain Catastrophising Scale, EQ-5D-3L, and measures of healthcare utilisation and costs. The trial is being conducted by the Department of Critical Care, University of Melbourne, and the Australian and New Zealand College of Anaesthetists Clinical Trials Network. The trial is funded by the Australian National Health and Medical Research Council. Discussion The ROCKet trial will clarify the effectiveness of ketamine in primary prevention of CPSP. In addition, it will provide high-quality, prospective data on the epidemiology of CPSP which will better inform further research into prevention and management of CPSP. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12617001619336) on the date of 12/11/2017.

Background Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease implicated in metastatic progression ostensibly due to its ability to degrade extracellular matrix (ECM) components and allow migration of cells through the basement membrane. Despite in vitro studies demonstrating this principle, this knowledge has not translated into the use of MMP inhibitors (MMPi) as effective cancer therapeutics, or been corroborated by evidence of in vivo ECM degradation mediated by MT1-MMP, suggesting that our understanding of the role of MT1-MMP in cancer progression is incomplete. Methods MCF-7 and MDA-MB 231 breast cancer cell lines were created that stably overexpress different levels of MT1-MMP. Using 2D culture, we analyzed proMMP-2 activation (gelatin zymography), ECM degradation (fluorescent gelatin), ERK signaling (immunoblot), cell migration (transwell/scratch closure/time-lapse imaging), and viability (colorimetric substrate) to assess how different MT1-MMP levels affect these cellular parameters. We also utilized Matrigel 3D cell culture and avian embryos to examine how different levels of MT1-MMP expression affect morphological changes in 3D culture, and tumourigenecity and extravasation efficiency in vivo . Results In 2D culture, breast cancer cells expressing high levels of MT1-MMP were capable of widespread ECM degradation and TIMP-2-mediated proMMP-2 activation, but were not the most migratory. Instead, cells expressing low levels of MT1-MMP were the most migratory, and demonstrated increased viability and ERK activation. In 3D culture, MCF-7 breast cancer cells expressing low levels of MT1-MMP demonstrated an invasive protrusive phenotype, whereas cells expressing high levels of MT1-MMP demonstrated loss of colony structure and cell fragment release. Similarly, in vivo analysis demonstrated increased tumourigenecity and metastatic capability for cells expressing low levels of MT1-MMP , whereas cells expressing high levels were devoid of these qualities despite the production of functional MT1-MMP protein. Conclusions This study demonstrates that excessive ECM degradation mediated by high levels of MT1-MMP is not associated with cell migration and tumourigenesis, while low levels of MT1-MMP promote invasion and vascularization in vivo.