Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Objectives: ：Among the various risk factors for suicide, geographic factors have different effects on males and females. This study aimed to identify differences between genders in spatiotemporal dependence and spatiotemporal patterns of suicide mortality over the preceding decade. Methods: ：This research analyzed the age-adjusted suicide mortality rate per 100,000 population, spanning from 2012 to 2021, for intentional suicides across each administrative district (229 Si, Gun, Gu) in Korea. Data were sourced from the National Statistical Office of the Korean Statistical Information Service. The Moran’s I in-dex for spatial autocorrelation of the suicide mortality rates was computed. An emerging hot spot analysis was conducted to examine the community-level spatiotemporal distribution patterns, thus providing insight into the re-gional clustering characteristics that reflect the temporal-spatial clusters of suicide mortality rates. Results: ：TIn males, the Moran’s I indices were almost above 0 (p-value<0.05) for most years, indicating sig-nificant spatial autocorrelation. Conversely, no significant regional clustering was observed among females dur-ing the same period. The emerging hot spot analysis, focusing on the temporal trends in the spatial distributionof male suicide mortality rates from 2012 to 2021, identified two distinct time series patterns and a total of 12 hot spot areas: seven new spots and five sporadic spots. Conclusions ：This study is the first to intuitively demonstrate the disparities in spatiotemporal dependencies and patterns of suicide mortality rates in Korea between genders. The findings highlight the necessity for tailoredsuicide prevention strategies that are sensitive to gender differences.

Objectives: Eveningness predominates in adolescence. Morningness has been reported to be associated with mental toughness via resilience. Morningness could be related to healthy sleep habits and a good personality. Methods: Sleep-related behaviors, such as weekend oversleep, social jetlag, and daytime sunlight exposure between 10:00 and 15:00, were evaluated using sleep-related questionnaires. Morningness-eveningness questionnaire, insomnia severity index, Epworth sleepiness scale, hospital anxiety and depression scale and defense style questionnaire were used. This study includes 1,610 high school students. Results: Multiple linear regression analysis revealed that morningness is predicted by male sex (β=0.115, t=4.769, p<0.001) and greater adaptive (β=0.092, t=3.506, p<0.001) and self-suppressive defense styles (β=0.072, t=2.192, p=0.029) and lesser immature defense styles (β=-0.163, t=-4.782, p<0.001) after controlling for age, sleep quality, depression, anxiety. Morningness is also predicted by greater sublimation (β=0.09, t=3.541, p<0.001) and reaction formation (β=0.112, t=4.488, p<0.001) and lesser consumption (β=-0.062, t=-2.501, p=0.012), passive aggression (β=-0.101, t=-3.747, p<0.001) and withdrawal (β=-0.084, t=-2.955, p=0.003), and male sex (β=0.117, t=4.896, p<0.001) after controlling for age, sleep quality, depression, and anxiety. Conclusion Morniness in adolescence may be related to a positive personality. Promoting morningness might be related to healthy development in personality.

Objectives: ：Among the various risk factors for suicide, geographic factors have different effects on males and females. This study aimed to identify differences between genders in spatiotemporal dependence and spatiotemporal patterns of suicide mortality over the preceding decade. Methods: ：This research analyzed the age-adjusted suicide mortality rate per 100,000 population, spanning from 2012 to 2021, for intentional suicides across each administrative district (229 Si, Gun, Gu) in Korea. Data were sourced from the National Statistical Office of the Korean Statistical Information Service. The Moran’s I in-dex for spatial autocorrelation of the suicide mortality rates was computed. An emerging hot spot analysis was conducted to examine the community-level spatiotemporal distribution patterns, thus providing insight into the re-gional clustering characteristics that reflect the temporal-spatial clusters of suicide mortality rates. Results: ：TIn males, the Moran’s I indices were almost above 0 (p-value<0.05) for most years, indicating sig-nificant spatial autocorrelation. Conversely, no significant regional clustering was observed among females dur-ing the same period. The emerging hot spot analysis, focusing on the temporal trends in the spatial distributionof male suicide mortality rates from 2012 to 2021, identified two distinct time series patterns and a total of 12 hot spot areas: seven new spots and five sporadic spots. Conclusions ：This study is the first to intuitively demonstrate the disparities in spatiotemporal dependencies and patterns of suicide mortality rates in Korea between genders. The findings highlight the necessity for tailoredsuicide prevention strategies that are sensitive to gender differences.