Background: The Act on Decisions on Life-Sustaining Treatment (LST) has been implemented in Korea since 2018, yet data on its application in neurocritical care units remain scarce. This study aimed to evaluate the clinical characteristics and outcomes of LST withdrawal or withholding in the neurocritical care unit. Methods: This study was a retrospective analysis conducted at a tertiary university hospital in Busan, South Korea. Among patients admitted to the neurocritical care unit between February 2018 and August 2023, those with documented decisions for LST withdrawal or withholding were enrolled. Demographic and clinical characteristics, underlying and combined conditions, reasons for LST decisions, measures taken, and time from LST withdrawal to death were extracted from medical records. Results: A total of 69 patients were included, with a median age of 67 years, and 38 (55%) were male. Cerebrovascular disease (62%) and traumatic brain injury (22%) were the most common underlying diagnoses. The primary reason for LST decisions was irreversible neurological damage (71%), followed by systemic complications (19%). Mechanical ventilation cessation (91%) and extubation (86%) were most frequently used measures for LST withdrawal. The median time from LST withdrawal to death was 22 minutes. Conclusions Our study demonstrates that LST decisions in the neurocritical care unit predominantly occur among patients with cerebrovascular disease or traumatic brain injury, mostly triggered by neurological deterioration. Most patients died shortly after withdrawal. These findings provide important insight into current LST withdrawal practices in neurocritical care and may assist clinical and ethical decision making in similar settings.

Purpose: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.