OBJECTIVES: Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. METHODS: We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. RESULTS: By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases. CONCLUSIONS The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

Purpose: To investigate the prevalence of copper, zinc, and vitamin D deficiencies in surgical intensive care unit (SICU) patients and the associations between those deficiencies and clinical outcomes. Methods: We conducted a retrospective study of 210 patients admitted to the SICU of Asan Medical Center between June 2020 and June 2022. Micronutrient levels were measured within 7 days of SICU admission. Primary outcomes were the mortality rate, length of SICU stay, hospital stay duration, and mechanical ventilation duration. Results: Copper deficiency was found in 35% (68/193), zinc deficiency in 52% (100/193), and severe vitamin D deficiency in 46% (82/179) of patients. Copper-deficient patients showed a significantly higher mortality rate (25.0% vs. 12.8%, P=0.044), longer hospital stays (57.8±47.0 vs. 45.2±36.6 days, P=0.041), and extended mechanical ventilation duration (26.9±23.3 vs. 18.8±15.7 days, P=0.012). Zinc deficiency was associated with higher C-reactive protein levels (16.2±9.5 vs. 11.5±8.8 mg/dL, P=0.001) and lower prealbumin levels (6.5±2.8 vs. 9.9±5.6 mg/dL, P<0.001). Severe vitamin D deficiency (<10 ng/mL) was not significantly associated with mortality or other clinical outcomes (mortality:<10 ng/mL vs. ≥10 ng/mL, 13% vs. 18%, P=0.583). Conclusion Micronutrient deficiencies are prevalent in SICU patients. Copper deficiency significantly correlated with poor clinical outcomes, and zinc deficiency showed a strong association with inflammatory markers. Early assessment and supplementation of micronutrients could be beneficial for critically ill surgical patients.

OBJECTIVES: Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. METHODS: We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. RESULTS: By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases. CONCLUSIONS The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

Purpose: To investigate the prevalence of copper, zinc, and vitamin D deficiencies in surgical intensive care unit (SICU) patients and the associations between those deficiencies and clinical outcomes. Methods: We conducted a retrospective study of 210 patients admitted to the SICU of Asan Medical Center between June 2020 and June 2022. Micronutrient levels were measured within 7 days of SICU admission. Primary outcomes were the mortality rate, length of SICU stay, hospital stay duration, and mechanical ventilation duration. Results: Copper deficiency was found in 35% (68/193), zinc deficiency in 52% (100/193), and severe vitamin D deficiency in 46% (82/179) of patients. Copper-deficient patients showed a significantly higher mortality rate (25.0% vs. 12.8%, P=0.044), longer hospital stays (57.8±47.0 vs. 45.2±36.6 days, P=0.041), and extended mechanical ventilation duration (26.9±23.3 vs. 18.8±15.7 days, P=0.012). Zinc deficiency was associated with higher C-reactive protein levels (16.2±9.5 vs. 11.5±8.8 mg/dL, P=0.001) and lower prealbumin levels (6.5±2.8 vs. 9.9±5.6 mg/dL, P<0.001). Severe vitamin D deficiency (<10 ng/mL) was not significantly associated with mortality or other clinical outcomes (mortality:<10 ng/mL vs. ≥10 ng/mL, 13% vs. 18%, P=0.583). Conclusion Micronutrient deficiencies are prevalent in SICU patients. Copper deficiency significantly correlated with poor clinical outcomes, and zinc deficiency showed a strong association with inflammatory markers. Early assessment and supplementation of micronutrients could be beneficial for critically ill surgical patients.

Purpose: To investigate the prevalence of copper, zinc, and vitamin D deficiencies in surgical intensive care unit (SICU) patients and the associations between those deficiencies and clinical outcomes. Methods: We conducted a retrospective study of 210 patients admitted to the SICU of Asan Medical Center between June 2020 and June 2022. Micronutrient levels were measured within 7 days of SICU admission. Primary outcomes were the mortality rate, length of SICU stay, hospital stay duration, and mechanical ventilation duration. Results: Copper deficiency was found in 35% (68/193), zinc deficiency in 52% (100/193), and severe vitamin D deficiency in 46% (82/179) of patients. Copper-deficient patients showed a significantly higher mortality rate (25.0% vs. 12.8%, P=0.044), longer hospital stays (57.8±47.0 vs. 45.2±36.6 days, P=0.041), and extended mechanical ventilation duration (26.9±23.3 vs. 18.8±15.7 days, P=0.012). Zinc deficiency was associated with higher C-reactive protein levels (16.2±9.5 vs. 11.5±8.8 mg/dL, P=0.001) and lower prealbumin levels (6.5±2.8 vs. 9.9±5.6 mg/dL, P<0.001). Severe vitamin D deficiency (<10 ng/mL) was not significantly associated with mortality or other clinical outcomes (mortality:<10 ng/mL vs. ≥10 ng/mL, 13% vs. 18%, P=0.583). Conclusion Micronutrient deficiencies are prevalent in SICU patients. Copper deficiency significantly correlated with poor clinical outcomes, and zinc deficiency showed a strong association with inflammatory markers. Early assessment and supplementation of micronutrients could be beneficial for critically ill surgical patients.

OBJECTIVES: Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. METHODS: We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. RESULTS: By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases. CONCLUSIONS The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

Purpose: To investigate the prevalence of copper, zinc, and vitamin D deficiencies in surgical intensive care unit (SICU) patients and the associations between those deficiencies and clinical outcomes. Methods: We conducted a retrospective study of 210 patients admitted to the SICU of Asan Medical Center between June 2020 and June 2022. Micronutrient levels were measured within 7 days of SICU admission. Primary outcomes were the mortality rate, length of SICU stay, hospital stay duration, and mechanical ventilation duration. Results: Copper deficiency was found in 35% (68/193), zinc deficiency in 52% (100/193), and severe vitamin D deficiency in 46% (82/179) of patients. Copper-deficient patients showed a significantly higher mortality rate (25.0% vs. 12.8%, P=0.044), longer hospital stays (57.8±47.0 vs. 45.2±36.6 days, P=0.041), and extended mechanical ventilation duration (26.9±23.3 vs. 18.8±15.7 days, P=0.012). Zinc deficiency was associated with higher C-reactive protein levels (16.2±9.5 vs. 11.5±8.8 mg/dL, P=0.001) and lower prealbumin levels (6.5±2.8 vs. 9.9±5.6 mg/dL, P<0.001). Severe vitamin D deficiency (<10 ng/mL) was not significantly associated with mortality or other clinical outcomes (mortality:<10 ng/mL vs. ≥10 ng/mL, 13% vs. 18%, P=0.583). Conclusion Micronutrient deficiencies are prevalent in SICU patients. Copper deficiency significantly correlated with poor clinical outcomes, and zinc deficiency showed a strong association with inflammatory markers. Early assessment and supplementation of micronutrients could be beneficial for critically ill surgical patients.

Purpose: To investigate the prevalence of copper, zinc, and vitamin D deficiencies in surgical intensive care unit (SICU) patients and the associations between those deficiencies and clinical outcomes. Methods: We conducted a retrospective study of 210 patients admitted to the SICU of Asan Medical Center between June 2020 and June 2022. Micronutrient levels were measured within 7 days of SICU admission. Primary outcomes were the mortality rate, length of SICU stay, hospital stay duration, and mechanical ventilation duration. Results: Copper deficiency was found in 35% (68/193), zinc deficiency in 52% (100/193), and severe vitamin D deficiency in 46% (82/179) of patients. Copper-deficient patients showed a significantly higher mortality rate (25.0% vs. 12.8%, P=0.044), longer hospital stays (57.8±47.0 vs. 45.2±36.6 days, P=0.041), and extended mechanical ventilation duration (26.9±23.3 vs. 18.8±15.7 days, P=0.012). Zinc deficiency was associated with higher C-reactive protein levels (16.2±9.5 vs. 11.5±8.8 mg/dL, P=0.001) and lower prealbumin levels (6.5±2.8 vs. 9.9±5.6 mg/dL, P<0.001). Severe vitamin D deficiency (<10 ng/mL) was not significantly associated with mortality or other clinical outcomes (mortality:<10 ng/mL vs. ≥10 ng/mL, 13% vs. 18%, P=0.583). Conclusion Micronutrient deficiencies are prevalent in SICU patients. Copper deficiency significantly correlated with poor clinical outcomes, and zinc deficiency showed a strong association with inflammatory markers. Early assessment and supplementation of micronutrients could be beneficial for critically ill surgical patients.

OBJECTIVES: Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. METHODS: We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. RESULTS: By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases. CONCLUSIONS The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.

Background: Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas. Methods: This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis. Results: In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively). Conclusions There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.