OBJECTIVE Investigate the effects of diazepam (DZP) on γ2 subunit containing GABA type A receptor (GABAAR) trafficking. METHODS Immunofluorescence microscopy measured surface GABAARs and gephyrin in rat cortical neurons after 24 h exposure of 1.0 μmol · L- 1 DZP. Biochemical studies of mice injected with 10 mg·kg-1 DZP vs vehicle were assessed for γ2 subunit and total gephyrin cortical levels 12 h post- injection. Ubiquitination of the γ2 subunit was studied by immunoprecipitation after 12 h of 1.0 μmol·L- 1 DZP exposure. A γ2 subunit encoding an N terminal fluorogen-activating peptide and pH-sensitive green fluorescent protein (γ2pHFAP) measured lysosomal targeting of γ2 containing GABAARs. RFP-gephyrin and γ2pHFAP synaptic diffusion rates were examined using fluorescence recovery after photobleaching (FRAP). RESULTS Extrasynaptic levels of γ2 GABAARs decreased by 12.2%, while synaptic gephyrin S270 phosphorylation increased by 18.3% in DZP-treated neurons after 24 h compared to control (P<0.05). Dendritic levels of gephyrin were also reduced to 74.1% of control, while S270 phosphorylation was elevated by 25.2% (P<0.05; P<0.01). Mice 12 h post-DZP injection demonstrated a 12.7% and 26.1% decrease in total γ2 and gephyrin levels, respectively (P<0.05; P<0.01). 12 h DZP treatment enhanced γ2 subunit ubiquitination 1.13-fold relative to control (P<0.05). Internalized γ2pHFAP GABAARs associated with lysosomes was 8.0% higher in neurons treated with 12-16 h DZP compared to control. Pilot FRAP experiments suggest gephyrin and γ2 have increased mobility and turnover at synapses following DZP. CONCLUSION DZP treatment decreases γ2 GABAAR levels and gephyrin scaffolding function after one day of exposure, which may contribute to the formation of DZP tolerance.

Methods: Clinical and neuromonitoring data of 207 consecutive adult patients who underwent cervical spine surgeries at multiple surgical centers using bimodal IONM were analyzed. Signal changes were divided into three groups. Group 0 had transient signal changes in either MEPs or SSEPs, group 1 had sustained unimodal changes, and group 2 had sustained changes in both MEPs and SSEPs. The incidences of true neurological deficits in each group were recorded. Results: A total of 25% (52/207) had IONM signal alerts. Out of these signal drops, 96% (50/52) were considered to be false positives. Groups 0 and 1 had no incidence of neurological deficits, while group 2 had a 29% (2/7) rate of true neurological deficits. The sensitivities of both MEP and SSEP were 100%. SSEP had a specificity of 96.6%, while MEP had a lower specificity at 76.6%. C5 palsy rate was 6%, and there was no correlation with IONM signal alerts (p=0.73). Conclusions This study shows that we can better predict its clinical significance by dividing IONM signal drops into three groups. A sustained, bimodal (MEP and SSEP) signal drop had the highest risk of true neurological deficits and warrants a high level of caution. There were no clear risk factors for false-positive alerts but there was a trend toward patients with cervical myelopathy.

Methods: Clinical and neuromonitoring data of 207 consecutive adult patients who underwent cervical spine surgeries at multiple surgical centers using bimodal IONM were analyzed. Signal changes were divided into three groups. Group 0 had transient signal changes in either MEPs or SSEPs, group 1 had sustained unimodal changes, and group 2 had sustained changes in both MEPs and SSEPs. The incidences of true neurological deficits in each group were recorded. Results: A total of 25% (52/207) had IONM signal alerts. Out of these signal drops, 96% (50/52) were considered to be false positives. Groups 0 and 1 had no incidence of neurological deficits, while group 2 had a 29% (2/7) rate of true neurological deficits. The sensitivities of both MEP and SSEP were 100%. SSEP had a specificity of 96.6%, while MEP had a lower specificity at 76.6%. C5 palsy rate was 6%, and there was no correlation with IONM signal alerts (p=0.73). Conclusions This study shows that we can better predict its clinical significance by dividing IONM signal drops into three groups. A sustained, bimodal (MEP and SSEP) signal drop had the highest risk of true neurological deficits and warrants a high level of caution. There were no clear risk factors for false-positive alerts but there was a trend toward patients with cervical myelopathy.

PURPOSE: The COVID-19 pandemic has caused 1.4 million deaths globally and is associated with a 3-4 times increase in 30-day mortality after a fragility hip fracture with concurrent COVID-19 infection. Typically, death from COVID-19 infection occurs between 15 and 22 days after the onset of symptoms, but this period can extend up to 8 weeks. This study aimed to assess the impact of concurrent COVID-19 infection on 120-day mortality after a fragility hip fracture. METHODS: A multi-centre prospective study across 10 hospitals treating 8% of the annual burden of hip fractures in England between 1st March and 30th April, 2020 was performed. Patients whose surgical treatment was payable through the National Health Service Best Practice Tariff mechanism for "fragility hip fractures" were included in the study. Patients' 120-day mortality was assessed relative to their peri-operative COVID-19 status. Statistical analysis was performed using SPSS version 27. RESULTS: A total of 746 patients were included in this study, of which 87 (11.7%) were COVID-19 positive. Mortality rates at 30- and 120-day were significantly higher for COVID-19 positive patients relative to COVID-19 negative patients (p < 0.001). However, mortality rates between 31 and 120-day were not significantly different (p = 0.107), 16.1% and 9.4% respectively for COVID-19 positive and negative patients, odds ratio 1.855 (95% CI 0.865-3.978). CONCLUSION Hip fracture patients with concurrent COVID-19 infection, provided that they are alive at day-31 after injury, have no significant difference in 120-day mortality. Despite the growing awareness and concern of "long-COVID" and its widespread prevalence, this does not appear to increase medium-term mortality rates after a hip fracture.
COVID-19 ; Hip Fractures/surgery* ; Humans ; Pandemics ; Prospective Studies ; Retrospective Studies ; State Medicine ; United Kingdom/epidemiology*