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Introduction Cognitive changes after anaesthesia and surgery, such as delirium and postoperative cognitive dysfunction (POCD), are common and lead to poor outcomes and increased healthcare costs. While several interventions for delirium exist, there are no effective treatment strategies for POCD. Understanding the risks and contributing factors may offer clinicians unique opportunities to better identify and develop preventative interventions for those at higher risk. Elderly patients undergoing orthopaedic surgery are at high risk of developing postoperative delirium (PD) and POCD. The incidence of POCD has not been rigorously studied in the total hip and knee arthroplasty (THA/TKA) population. Therefore, we have designed a prospective, observational cohort study to assess POCD in patients undergoing THA/TKA, both increasingly common procedures. The incidence of PD and POCD in a high volume, tertiary care arthroplasty centre will be determined and associated risk factors will be identified. Methods and analysis Cognitive function will be tested with a computer-based cognitive assessment tool [CogState Brief Battery], preoperatively at baseline and postoperatively while in hospital at (<3 days), 6 weeks and 4.5 months. The primary outcome is the incidence of postoperative cognitive decline at 4.5 months. Logistic regression analysis is planned to test the association of POCD with several potential risk factors. In addition, delirium will be assessed preoperatively and postoperatively in the hospital using the Confusion Assessment Method (3D-CAM). Ethics and dissemination The protocol for this prospective observational study was approved by the Sunnybrook Health Sciences Centre Research Ethics Board (REB#: 040-2017). Recruitment commenced in May 2017 and will continue until 2019. The results will be disseminated in a peer-reviewed journal and in scientific meetings. Trial registration number NCT03147937. [ABSTRACT FROM AUTHOR]

Summary: Systemic inflammation causes learning and memory deficits through mechanisms that remain poorly understood. Here, we studied the pathogenesis of memory loss associated with inflammation and found that we could reverse memory deficits by pharmacologically inhibiting α5-subunit-containing γ-aminobutyric acid type A (α5GABAA) receptors and deleting the gene associated with the α5 subunit. Acute inflammation reduces long-term potentiation, a synaptic correlate of memory, in hippocampal slices from wild-type mice, and this reduction was reversed by inhibition of α5GABAA receptor function. A tonic inhibitory current generated by α5GABAA receptors in hippocampal neurons was increased by the key proinflammatory cytokine interleukin-1β through a p38 mitogen-activated protein kinase signaling pathway. Interleukin-1β also increased the surface expression of α5GABAA receptors in the hippocampus. Collectively, these results show that α5GABAA receptor activity increases during inflammation and that this increase is critical for inflammation-induced memory deficits. [ABSTRACT FROM AUTHOR]

Acute cerebral cortical trauma often leads to paroxysmal activities that terminate in a few hours, but several months later, patients can develop epilepsy. The process occurring between the initial acute triggered seizures and the onset of spontaneous unprovoked seizures is termed epileptogenesis. Here the authors summarize recent morphological, electrophysiological, and computational studies demonstrating that partial cortical isolation increases the number and duration of silent states in the cortical network, boosting neuronal connectivity and network excitability. These changes develop progressively, and after several weeks their synergetic action leads to epilepsy. [ABSTRACT FROM AUTHOR]

Traumatic brain injuries are often followed by abnormal hyperexcitability, leading to acute seizures and epilepsy. Previous studies documented the rewiring capacity of neocortical neurons in response to various cortical and subcortical lesions. However, little information is available on the functional consequences of these anatomical changes after cortical trauma and the adaptation of synaptic connectivity to a decreased input produced by chronic deafferentation. In this study, we recorded intracellular (IC) activities of cortical neurons simultaneously with extracellular (EC) unit activities and field potentials of neighboring cells in cat cortex, after a large transection of the white matter underneath the suprasylvian gyrus, in acute and chronic conditions (at 2, 4, and 6 weeks) in ketamine-xylazineanesthetized cats. Using EC spikes to compute the spike-triggered averages of IC membrane potential, we found an increased connection probability and efficacy between cortical neurons weeks after cortical trauma. Inhibitory interactions showed no significant changes in the traumatized cortex compared with control. The increased synaptic efficacy was accompanied by enhanced input resistance and intrinsic excitability of cortical neurons, as well as by increased duration of silent network periods. Our electrophysiological data revealed functional consequences of previously reported anatomical changes in the injured cortex.Wesuggest that homeostatic synaptic plasticity compensating the decreased activity in the undercut cortex leads to an uncontrollable cortical hyperexcitability and seizure generation. [ABSTRACT FROM AUTHOR]

Introduction: Tranexamic acid (TXA) is an inexpensive and widely available medication that reduces blood loss and red blood cell (RBC) transfusion in cardiac and orthopaedic surgeries. While the use of TXA in these surgeries is routine, its efficacy and safety in other surgeries, including oncologic surgeries, with comparable rates of transfusion are uncertain. Our primary objective is to evaluate whether a hospital-level policy implementation of routine TXA use in patients undergoing major non-cardiac surgery reduces RBC transfusion without increasing thrombotic risk., Methods and Analysis: A pragmatic, registry-based, blinded, cluster-crossover randomised controlled trial at 10 Canadian sites, enrolling patients undergoing non-cardiac surgeries at high risk for RBC transfusion. Sites are randomised in 4-week intervals to a hospital policy of intraoperative TXA or matching placebo. TXA is administered as 1 g at skin incision, followed by an additional 1 g prior to skin closure. Coprimary outcomes are (1) effectiveness, evaluated as the proportion of patients transfused RBCs during hospital admission and (2) safety, evaluated as the proportion of patients diagnosed with venous thromboembolism within 90 days. Secondary outcomes include: (1) transfusion: number of RBC units transfused (both at a hospital and patient level); (2) safety: in-hospital diagnoses of myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism; (3) clinical: hospital length of stay, intensive care unit admission, hospital survival, 90-day survival and the number of days alive and out of hospital to day 30; and (4) compliance: the proportion of enrolled patients who receive a minimum of one dose of the study intervention., Ethics and Dissemination: Institutional research ethics board approval has been obtained at all sites. At the completion of the trial, a plain language summary of the results will be posted on the trial website and distributed in the lay press. Our trial results will be published in a peer-reviewed scientific journal., Trial Registration Number: NCT04803747., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)