Purpose: There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the epidermal growth factor receptor (EGFR) mutation. Materials and Methods: A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue. Results: In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22.0%, 9.8%, and 29.3%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 36.6%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 82.9% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation. Conclusion We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

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.

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: Patients with septic shock frequently require tracheal intubation in the emergency department (ED). However, the criteria for tracheal intubation are subjective, based on physician experience, or require serial evaluations over relatively long intervals to make accurate predictions, which might not be feasible in the ED. We used supervised learning approaches and features routinely available during the initial stages of evaluation and resuscitation to stratify the risks of tracheal intubation within a 24-hour time window. Methods: We retrospectively analyzed the data of patients diagnosed with septic shock based on the SEPSIS-3 criteria across 21 university hospital EDs in the Republic of Korea. A principal component analysis revealed a complex, non-linear decision boundary with respect to the application of tracheal intubation within a 24-hour time window. Stratified five-fold cross validation and a grid search were used with extreme gradient boost. Shapley values were calculated to explain feature importance and preferences. Results: In total, data for 4,762 patients were analyzed; within that population, 1,486 (31%) were intubated within a 24-hour window, and 3,276 (69%) were not. The area under the receiver operating characteristic curve and F1 scores for intubation within a 24-hour window were 0.829 (95% CI, 0.801–0.878) and 0.654 (95% CI, 0.627–0.681), respectively. The Shapley values identified lactate level after initial fluids, suspected lung infection, initial pH, Sequential Organ Failure Assessment score at enrollment, and respiratory rate at enrollment as important features for prediction. Conclusions An extreme gradient boosting machine can moderately discriminate whether intubation is warranted within 24 hours of the recognition of septic shock in the ED.