Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues

Dysfunction of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 subunit and deficits in synaptic plasticity are implicated in schizophrenia and sleep and circadian rhythm disruption. To investigate the role of GluA1 in circadian and sleep behaviour, we used wheel-running, passive-infrared, and video-based home-cage activity monitoring to assess daily rest–activity profiles of GluA1-knockout mice (Gria1−/−). We showed that these mice displayed various circadian abnormalities, including misaligned, fragmented, and more variable rest–activity patterns. In addition, they showed heightened, but transient, behavioural arousal to light→dark and dark→light transitions, as well as attenuated nocturnal-light-induced activity suppression (negative masking). In the hypothalamic suprachiasmatic nuclei (SCN), nocturnal-light-induced cFos signals (a molecular marker of neuronal activity in the preceding ~1–2 h) were attenuated, indicating reduced light sensitivity in the SCN. However, there was no change in the neuroanatomical distribution of expression levels of two neuropeptides―vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP)―differentially expressed in the core (ventromedial) vs. shell (dorsolateral) SCN subregions and both are known to be important for neuronal synchronisation within the SCN and circadian rhythmicity. In the motor cortex (area M1/M2), there was increased inter-individual variability in cFos levels during the evening period, mirroring the increased inter-individual variability in locomotor activity under nocturnal light. Finally, in the spontaneous odour recognition task GluA1 knockouts’ short-term memory was impaired due to enhanced attention to the recently encountered familiar odour. These abnormalities due to altered AMPA-receptor-mediated signalling resemble and may contribute to sleep and circadian rhythm disruption and attentional deficits in different modalities in schizophrenia

Absent sleep EEG spindle activity in GluA1 (Gria1) knockout mice:relevance to neuropsychiatric disorders

Sleep EEG spindles have been implicated in attention, sensory processing, synaptic plasticity and memory consolidation. In humans, deficits in sleep spindles have been reported in a wide range of neurological and psychiatric disorders, including schizophrenia. Genome-wide association studies have suggested a link between schizophrenia and genes associated with synaptic plasticity, including the Gria1 gene which codes for the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Gria1−/− mice exhibit a phenotype relevant for neuropsychiatric disorders, including reduced synaptic plasticity and, at the behavioural level, attentional deficits leading to aberrant salience. In this study we report a striking reduction of EEG power density including the spindle-frequency range (10–15 Hz) during sleep in Gria1−/− mice. The reduction of spindle-activity in Gria1−/− mice was accompanied by longer REM sleep episodes, increased EEG slow-wave activity in the occipital derivation during baseline sleep, and a reduced rate of decline of EEG slow wave activity (0.5–4 Hz) during NREM sleep after sleep deprivation. These data provide a novel link between glutamatergic dysfunction and sleep abnormalities in a schizophrenia-relevant mouse model

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Risk prediction strategies using intraoperative physiological data in adults undergoing surgery: A systematic review study protocol

Postoperative mortality accounts for 7.7% of all deaths globally, while postoperative complications increase 1-year mortality by 60%. Risk prediction models for postoperative complications and mortality can facilitate tailored risk mitigation strategies. However, most models incorporate only preoperative patient-related factors as predictors and do not capture dynamic risks or changes that occur intraoperatively. This systematic review seeks to evaluate the predictive capability of intraoperative physiology derived from routine anaesthetic monitoring and the feature extraction methods for these variables. This review will include both prospective and retrospective studies that incorporate intraoperative physiological measurements into the development, validation or updating of a statistical prediction model, to identify those at risk of major end-organ (cardiovascular, pulmonary, renal, and neurological) complications and mortality up-to 90 days postoperatively. We will identify models developed in two settings: those undergoing cardiac surgery and heterogeneous adult patient cohorts undergoing non-cardiac surgery. The review will be reported according to the 2020 PRISMA guidelines. This review will evaluate the available literature on intraoperative physiology as predictor variables, to improve feature extraction methods for risk prediction models development while understanding how to capitalise on the vast routinely collected intraoperative physiological data sets that are increasingly available. This review is registered on PROSPERO, registration number CRD42023474384

Risk prediction strategies using intraoperative physiological data in adults undergoing surgery: a systematic review study protocol

Acknowledgements: The authors would like to thank Ms Eleanor Barker, assistant librarian at the University of Cambridge Medical Library for her help with the design of the search strategy in this systematic review.Abstract Postoperative mortality accounts for 7.7% of all global deaths, while postoperative complications increase 1-year mortality by 60%. Risk prediction models for postoperative complications and mortality can facilitate tailored risk mitigation strategies. However, most models incorporate only preoperative patient-related factors as predictors and do not capture dynamic risks or intraoperative events. This systematic review seeks to evaluate the predictive capability of intraoperative physiology derived from routine anaesthetic monitoring and the feature extraction methods for these variables. This review will include both prospective and retrospective studies that incorporate intraoperative physiological measurements into the development, validation or updating of a statistical prediction model, to identify those at risk of major end-organ (cardiovascular, pulmonary, renal and neurological) complications and mortality up-to 90 days postoperatively. We will identify models developed in two settings: those undergoing cardiac surgery and heterogeneous adult patient cohorts undergoing non-cardiac surgery. The review will be reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This review will evaluate the available literature on intraoperative physiology as predictor variables, to improve feature extraction methods for risk prediction models development while understanding how to capitalize on the vast routinely collected intraoperative physiological data sets that are increasingly available. This review is registered on PROSPERO, registration number CRD42023474384.</jats:p

Risk prediction strategies using intraoperative physiological data in adults undergoing surgery: a systematic review study protocol

Acknowledgements: The authors would like to thank Ms Eleanor Barker, assistant librarian at the University of Cambridge Medical Library for her help with the design of the search strategy in this systematic review.Abstract Postoperative mortality accounts for 7.7% of all global deaths, while postoperative complications increase 1-year mortality by 60%. Risk prediction models for postoperative complications and mortality can facilitate tailored risk mitigation strategies. However, most models incorporate only preoperative patient-related factors as predictors and do not capture dynamic risks or intraoperative events. This systematic review seeks to evaluate the predictive capability of intraoperative physiology derived from routine anaesthetic monitoring and the feature extraction methods for these variables. This review will include both prospective and retrospective studies that incorporate intraoperative physiological measurements into the development, validation or updating of a statistical prediction model, to identify those at risk of major end-organ (cardiovascular, pulmonary, renal and neurological) complications and mortality up-to 90 days postoperatively. We will identify models developed in two settings: those undergoing cardiac surgery and heterogeneous adult patient cohorts undergoing non-cardiac surgery. The review will be reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This review will evaluate the available literature on intraoperative physiology as predictor variables, to improve feature extraction methods for risk prediction models development while understanding how to capitalize on the vast routinely collected intraoperative physiological data sets that are increasingly available. This review is registered on PROSPERO, registration number CRD42023474384.</jats:p

Abstracts of the 4th Annual Graduate Entry Research in Medicine Conference

This book contains the abstracts of the papers presented at The 4th Annual Graduate Entry Research in Medicine Conference (GERMCON 2021) Organized by Warwick Medical School, University of Warwick in collaboration with Swansea University Medical School, Swansea University, Wales, UK held on 11th September 2021. This event has been designed with the intention of supporting students to develop their interests and skills within academic medicine. This was especially important for Graduate Entry Medical (GEM) students, who have less opportunity and time to engage in research due to their accelerated medical degree. Conference Title: 4th Annual Graduate Entry Research in Medicine ConferenceConference Acronym: GERMCON 2021Conference Date: 11 September 2021Conference Location: Scarman Conference Centre, The University of Warwick, England, CV4 7SH, UK.Conference Organizer: Warwick Medical School, University of Warwick, UKCo-organizer: Swansea University Medical School, Swansea University, Wales, UK Other Abstract Book of GERMCON: Abstracts of the 3rd Annual Graduate Entry Research in Medicine Conferenc