Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Liver disease causes over two million deaths annually worldwide, comprising approximately 4% of all global fatalities. We aimed to analyze liver disease-related mortality trends from 1990 to 2021 using the World Health Organization (WHO) Mortality Database and forecast global liver disease-related mortality rates up to 2050. Methods: This study examined age-standardized liver disease-related death rates from 1990 to 2021, employing data from the WHO Mortality Database across 112 countries across five continents. The rates over time were calculated using a locally weighted scatter plot smoother curve, with weights assigned based on the population of each country. Furthermore, this study projected liver disease-related mortality rates up to 2050 using a Bayesian age-periodcohort (BAPC) model. Additionally, a decomposition analysis was conducted to discern influencing factors such as population growth, aging, and epidemiological changes. Results: The estimated global age-standardized liver disease-related mortality rates surged significantly from 1990 to 2021 across 112 countries, rising from 103.4 deaths per 1,000,000 people (95% confidence interval [CI], 88.16, 118.74) in 1990 to 173.0 deaths per 1,000,000 people (95% CI, 155.15, 190.95) in 2021. This upward trend was particularly pronounced in low- and middle-income countries, in Africa, and in populations aged 65 years and older.Moreover, age-standardized liver disease-related mortality rates were correlated with a lower Human Development Index (P < 0.001) and sociodemographic index (P = 0.001). According to the BAPC model, the projected trend indicated a sustained and substantial decline in liver disease-related mortality rates, with an estimated decrease from 185.08 deaths per 1,000,000 people (95% CI, 179.79, 190.63) in 2021 to 156.29 (112.32, 214.77) in 2050. From 1990 to 2021, age-standardized liver disease-related deaths surged primarily due to epidemiological changes, whereas from 1990 to 2050, the impact of population aging and growth became the primary contributing factors to the overall increase. Conclusion Global age-standardized liver disease-related mortality has increased significantly and continues to emerge as a crucial global public health issue. Further investigation into liver disease-related mortality rates in Africa is needed, and updating policies is necessary to effectively manage the global burden of liver disease.

Background: Liver disease causes over two million deaths annually worldwide, comprising approximately 4% of all global fatalities. We aimed to analyze liver disease-related mortality trends from 1990 to 2021 using the World Health Organization (WHO) Mortality Database and forecast global liver disease-related mortality rates up to 2050. Methods: This study examined age-standardized liver disease-related death rates from 1990 to 2021, employing data from the WHO Mortality Database across 112 countries across five continents. The rates over time were calculated using a locally weighted scatter plot smoother curve, with weights assigned based on the population of each country. Furthermore, this study projected liver disease-related mortality rates up to 2050 using a Bayesian age-periodcohort (BAPC) model. Additionally, a decomposition analysis was conducted to discern influencing factors such as population growth, aging, and epidemiological changes. Results: The estimated global age-standardized liver disease-related mortality rates surged significantly from 1990 to 2021 across 112 countries, rising from 103.4 deaths per 1,000,000 people (95% confidence interval [CI], 88.16, 118.74) in 1990 to 173.0 deaths per 1,000,000 people (95% CI, 155.15, 190.95) in 2021. This upward trend was particularly pronounced in low- and middle-income countries, in Africa, and in populations aged 65 years and older.Moreover, age-standardized liver disease-related mortality rates were correlated with a lower Human Development Index (P < 0.001) and sociodemographic index (P = 0.001). According to the BAPC model, the projected trend indicated a sustained and substantial decline in liver disease-related mortality rates, with an estimated decrease from 185.08 deaths per 1,000,000 people (95% CI, 179.79, 190.63) in 2021 to 156.29 (112.32, 214.77) in 2050. From 1990 to 2021, age-standardized liver disease-related deaths surged primarily due to epidemiological changes, whereas from 1990 to 2050, the impact of population aging and growth became the primary contributing factors to the overall increase. Conclusion Global age-standardized liver disease-related mortality has increased significantly and continues to emerge as a crucial global public health issue. Further investigation into liver disease-related mortality rates in Africa is needed, and updating policies is necessary to effectively manage the global burden of liver disease.

Background: Liver disease causes over two million deaths annually worldwide, comprising approximately 4% of all global fatalities. We aimed to analyze liver disease-related mortality trends from 1990 to 2021 using the World Health Organization (WHO) Mortality Database and forecast global liver disease-related mortality rates up to 2050. Methods: This study examined age-standardized liver disease-related death rates from 1990 to 2021, employing data from the WHO Mortality Database across 112 countries across five continents. The rates over time were calculated using a locally weighted scatter plot smoother curve, with weights assigned based on the population of each country. Furthermore, this study projected liver disease-related mortality rates up to 2050 using a Bayesian age-periodcohort (BAPC) model. Additionally, a decomposition analysis was conducted to discern influencing factors such as population growth, aging, and epidemiological changes. Results: The estimated global age-standardized liver disease-related mortality rates surged significantly from 1990 to 2021 across 112 countries, rising from 103.4 deaths per 1,000,000 people (95% confidence interval [CI], 88.16, 118.74) in 1990 to 173.0 deaths per 1,000,000 people (95% CI, 155.15, 190.95) in 2021. This upward trend was particularly pronounced in low- and middle-income countries, in Africa, and in populations aged 65 years and older.Moreover, age-standardized liver disease-related mortality rates were correlated with a lower Human Development Index (P < 0.001) and sociodemographic index (P = 0.001). According to the BAPC model, the projected trend indicated a sustained and substantial decline in liver disease-related mortality rates, with an estimated decrease from 185.08 deaths per 1,000,000 people (95% CI, 179.79, 190.63) in 2021 to 156.29 (112.32, 214.77) in 2050. From 1990 to 2021, age-standardized liver disease-related deaths surged primarily due to epidemiological changes, whereas from 1990 to 2050, the impact of population aging and growth became the primary contributing factors to the overall increase. Conclusion Global age-standardized liver disease-related mortality has increased significantly and continues to emerge as a crucial global public health issue. Further investigation into liver disease-related mortality rates in Africa is needed, and updating policies is necessary to effectively manage the global burden of liver disease.

Background: Liver disease causes over two million deaths annually worldwide, comprising approximately 4% of all global fatalities. We aimed to analyze liver disease-related mortality trends from 1990 to 2021 using the World Health Organization (WHO) Mortality Database and forecast global liver disease-related mortality rates up to 2050. Methods: This study examined age-standardized liver disease-related death rates from 1990 to 2021, employing data from the WHO Mortality Database across 112 countries across five continents. The rates over time were calculated using a locally weighted scatter plot smoother curve, with weights assigned based on the population of each country. Furthermore, this study projected liver disease-related mortality rates up to 2050 using a Bayesian age-periodcohort (BAPC) model. Additionally, a decomposition analysis was conducted to discern influencing factors such as population growth, aging, and epidemiological changes. Results: The estimated global age-standardized liver disease-related mortality rates surged significantly from 1990 to 2021 across 112 countries, rising from 103.4 deaths per 1,000,000 people (95% confidence interval [CI], 88.16, 118.74) in 1990 to 173.0 deaths per 1,000,000 people (95% CI, 155.15, 190.95) in 2021. This upward trend was particularly pronounced in low- and middle-income countries, in Africa, and in populations aged 65 years and older.Moreover, age-standardized liver disease-related mortality rates were correlated with a lower Human Development Index (P < 0.001) and sociodemographic index (P = 0.001). According to the BAPC model, the projected trend indicated a sustained and substantial decline in liver disease-related mortality rates, with an estimated decrease from 185.08 deaths per 1,000,000 people (95% CI, 179.79, 190.63) in 2021 to 156.29 (112.32, 214.77) in 2050. From 1990 to 2021, age-standardized liver disease-related deaths surged primarily due to epidemiological changes, whereas from 1990 to 2050, the impact of population aging and growth became the primary contributing factors to the overall increase. Conclusion Global age-standardized liver disease-related mortality has increased significantly and continues to emerge as a crucial global public health issue. Further investigation into liver disease-related mortality rates in Africa is needed, and updating policies is necessary to effectively manage the global burden of liver disease.

Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Background/Aims: Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD. Methods: Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing. Results: Methylome and transcriptome analyses of liver biopsies revealed significant (p<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA<, and SERPING1, as well as hypomethylation (p<0.0005) and upregulation (p<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data. Conclusions Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.