Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl-D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors. In addition, numerous neurological disorders, including persistent neuropathic pain, multiple sclerosis, and seizures, have altered the levels of neurosteroids in the central nervous system. Thus, we review how local synthesis and metabolism of neurosteroids are modulated in the central nervous system and describe the role of neurosteroids under pathological conditions. Furthermore, we discuss whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders.

Background/Aims: Tracheostomy is a crucial intervention for severe pneumonia patients requiring prolonged mechanical ventilation (MV). However, debate persists regarding the influence of tracheostomy timing and performance on long-term survival outcomes. This study utilized propensity score matching to assess the impact of tracheostomy timing and performance on patient survival outcomes. Methods: A retrospective observational study employing propensity score matching was conducted of respiratory intensive care unit (ICU) patients who underwent prolonged acute MV due to severe pneumonia from 2008 to 2023. The primary outcome was the 90-day cumulative mortality rate, with secondary outcomes including ICU medical resource utilization rates. Results: Out of 1,078 patients, 545 underwent tracheostomy with a median timing of 7 days. The tracheostomy group exhibited lower 90-day cumulative mortality and a higher survival probability (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.43–0.63) than the no-tracheostomy group. The tracheostomy group had higher ICU medical resource utilization rates and medical expenditures. The early tracheostomy group (≤ 7 days) had lower ICU medical resource utilization rates and medical expenditures than the late tracheostomy group (> 7 days). However, there were no significant differences in the 90-day cumulative mortality rate and survival probability based on tracheostomy timing (HR 0.94, 95% CI 0.70–1.28). Conclusions Tracheostomy in patients with severe pneumonia requiring prolonged MV significantly reduced the 90-day mortality rate, and early tracheostomy may offer additional benefits for resource utilization efficiency. These findings underscore the importance of considering tracheostomy timing in optimizing patient outcomes and healthcare resource allocation.

Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl-D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors. In addition, numerous neurological disorders, including persistent neuropathic pain, multiple sclerosis, and seizures, have altered the levels of neurosteroids in the central nervous system. Thus, we review how local synthesis and metabolism of neurosteroids are modulated in the central nervous system and describe the role of neurosteroids under pathological conditions. Furthermore, we discuss whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders.

Background/Aims: Tracheostomy is a crucial intervention for severe pneumonia patients requiring prolonged mechanical ventilation (MV). However, debate persists regarding the influence of tracheostomy timing and performance on long-term survival outcomes. This study utilized propensity score matching to assess the impact of tracheostomy timing and performance on patient survival outcomes. Methods: A retrospective observational study employing propensity score matching was conducted of respiratory intensive care unit (ICU) patients who underwent prolonged acute MV due to severe pneumonia from 2008 to 2023. The primary outcome was the 90-day cumulative mortality rate, with secondary outcomes including ICU medical resource utilization rates. Results: Out of 1,078 patients, 545 underwent tracheostomy with a median timing of 7 days. The tracheostomy group exhibited lower 90-day cumulative mortality and a higher survival probability (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.43–0.63) than the no-tracheostomy group. The tracheostomy group had higher ICU medical resource utilization rates and medical expenditures. The early tracheostomy group (≤ 7 days) had lower ICU medical resource utilization rates and medical expenditures than the late tracheostomy group (> 7 days). However, there were no significant differences in the 90-day cumulative mortality rate and survival probability based on tracheostomy timing (HR 0.94, 95% CI 0.70–1.28). Conclusions Tracheostomy in patients with severe pneumonia requiring prolonged MV significantly reduced the 90-day mortality rate, and early tracheostomy may offer additional benefits for resource utilization efficiency. These findings underscore the importance of considering tracheostomy timing in optimizing patient outcomes and healthcare resource allocation.

Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl-D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors. In addition, numerous neurological disorders, including persistent neuropathic pain, multiple sclerosis, and seizures, have altered the levels of neurosteroids in the central nervous system. Thus, we review how local synthesis and metabolism of neurosteroids are modulated in the central nervous system and describe the role of neurosteroids under pathological conditions. Furthermore, we discuss whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders.

Background/Aims: Tracheostomy is a crucial intervention for severe pneumonia patients requiring prolonged mechanical ventilation (MV). However, debate persists regarding the influence of tracheostomy timing and performance on long-term survival outcomes. This study utilized propensity score matching to assess the impact of tracheostomy timing and performance on patient survival outcomes. Methods: A retrospective observational study employing propensity score matching was conducted of respiratory intensive care unit (ICU) patients who underwent prolonged acute MV due to severe pneumonia from 2008 to 2023. The primary outcome was the 90-day cumulative mortality rate, with secondary outcomes including ICU medical resource utilization rates. Results: Out of 1,078 patients, 545 underwent tracheostomy with a median timing of 7 days. The tracheostomy group exhibited lower 90-day cumulative mortality and a higher survival probability (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.43–0.63) than the no-tracheostomy group. The tracheostomy group had higher ICU medical resource utilization rates and medical expenditures. The early tracheostomy group (≤ 7 days) had lower ICU medical resource utilization rates and medical expenditures than the late tracheostomy group (> 7 days). However, there were no significant differences in the 90-day cumulative mortality rate and survival probability based on tracheostomy timing (HR 0.94, 95% CI 0.70–1.28). Conclusions Tracheostomy in patients with severe pneumonia requiring prolonged MV significantly reduced the 90-day mortality rate, and early tracheostomy may offer additional benefits for resource utilization efficiency. These findings underscore the importance of considering tracheostomy timing in optimizing patient outcomes and healthcare resource allocation.

Background/Aims: Tracheostomy is a crucial intervention for severe pneumonia patients requiring prolonged mechanical ventilation (MV). However, debate persists regarding the influence of tracheostomy timing and performance on long-term survival outcomes. This study utilized propensity score matching to assess the impact of tracheostomy timing and performance on patient survival outcomes. Methods: A retrospective observational study employing propensity score matching was conducted of respiratory intensive care unit (ICU) patients who underwent prolonged acute MV due to severe pneumonia from 2008 to 2023. The primary outcome was the 90-day cumulative mortality rate, with secondary outcomes including ICU medical resource utilization rates. Results: Out of 1,078 patients, 545 underwent tracheostomy with a median timing of 7 days. The tracheostomy group exhibited lower 90-day cumulative mortality and a higher survival probability (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.43–0.63) than the no-tracheostomy group. The tracheostomy group had higher ICU medical resource utilization rates and medical expenditures. The early tracheostomy group (≤ 7 days) had lower ICU medical resource utilization rates and medical expenditures than the late tracheostomy group (> 7 days). However, there were no significant differences in the 90-day cumulative mortality rate and survival probability based on tracheostomy timing (HR 0.94, 95% CI 0.70–1.28). Conclusions Tracheostomy in patients with severe pneumonia requiring prolonged MV significantly reduced the 90-day mortality rate, and early tracheostomy may offer additional benefits for resource utilization efficiency. These findings underscore the importance of considering tracheostomy timing in optimizing patient outcomes and healthcare resource allocation.

Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl-D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors. In addition, numerous neurological disorders, including persistent neuropathic pain, multiple sclerosis, and seizures, have altered the levels of neurosteroids in the central nervous system. Thus, we review how local synthesis and metabolism of neurosteroids are modulated in the central nervous system and describe the role of neurosteroids under pathological conditions. Furthermore, we discuss whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders.

Background/Aims: Tracheostomy is a crucial intervention for severe pneumonia patients requiring prolonged mechanical ventilation (MV). However, debate persists regarding the influence of tracheostomy timing and performance on long-term survival outcomes. This study utilized propensity score matching to assess the impact of tracheostomy timing and performance on patient survival outcomes. Methods: A retrospective observational study employing propensity score matching was conducted of respiratory intensive care unit (ICU) patients who underwent prolonged acute MV due to severe pneumonia from 2008 to 2023. The primary outcome was the 90-day cumulative mortality rate, with secondary outcomes including ICU medical resource utilization rates. Results: Out of 1,078 patients, 545 underwent tracheostomy with a median timing of 7 days. The tracheostomy group exhibited lower 90-day cumulative mortality and a higher survival probability (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.43–0.63) than the no-tracheostomy group. The tracheostomy group had higher ICU medical resource utilization rates and medical expenditures. The early tracheostomy group (≤ 7 days) had lower ICU medical resource utilization rates and medical expenditures than the late tracheostomy group (> 7 days). However, there were no significant differences in the 90-day cumulative mortality rate and survival probability based on tracheostomy timing (HR 0.94, 95% CI 0.70–1.28). Conclusions Tracheostomy in patients with severe pneumonia requiring prolonged MV significantly reduced the 90-day mortality rate, and early tracheostomy may offer additional benefits for resource utilization efficiency. These findings underscore the importance of considering tracheostomy timing in optimizing patient outcomes and healthcare resource allocation.

Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl-D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors. In addition, numerous neurological disorders, including persistent neuropathic pain, multiple sclerosis, and seizures, have altered the levels of neurosteroids in the central nervous system. Thus, we review how local synthesis and metabolism of neurosteroids are modulated in the central nervous system and describe the role of neurosteroids under pathological conditions. Furthermore, we discuss whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders.