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: 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: 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: We aimed to assess the impact of obesity on mortality in middle-aged Koreans using data from a Health Examinees study. METHODS: We used data from the participants who had complete information on body size and gave informed consent for the linkage of their data with the national death certificate data. Cox proportional hazard model was used to estimate the hazard ratios and 95% confidence intervals (CIs) of body mass index (BMI) and waist-to-hip ratio (WHR) for all-cause, cardiovascular, and cancer mortality. RESULTS: A total of 115,961 participants were included in the study. The results showed a U-shaped association between BMI and mortality, indicating that both males and females with BMIs of less than 21.0 kg/m2 and greater than or equal to 30.0 kg/m2 are at increased risk. The results showed that males with a BMI of less than 18.5 kg/m² had a significantly higher risk of all-cause mortality (adjusted hazard ratio [aHR], 2.24; 95% CI, 1.73 to 2.91) and cardiovascular mortality (aHR, 2.27; 95% CI, 1.23 to 4.20). Similarly, males with a WHR of less than 0.80 (aHR, 1.38; 95% CI, 1.08 to 1.77), 0.90 to less than 0.95 (aHR, 1.15; 95% CI, 1.02 to 1.29), and greater than or equal to 0.95 (aHR, 1.28; 95% CI, 1.11 to 1.47) showed an increased risk of all-cause mortality. In females, a BMI of less than 18.0 kg/m2 was linked to a higher risk of cardiovascular mortality (aHR, 2.67; 95% CI, 1.13 to 6.33). CONCLUSIONS Being underweight was associated with an increased risk of mortality in both sexes, and the lowest risk of death was found in males who were slightly overweight with a BMI of 23.0-25.0 kg/m2.

OBJECTIVES: We aimed to assess the impact of obesity on mortality in middle-aged Koreans using data from a Health Examinees study. METHODS: We used data from the participants who had complete information on body size and gave informed consent for the linkage of their data with the national death certificate data. Cox proportional hazard model was used to estimate the hazard ratios and 95% confidence intervals (CIs) of body mass index (BMI) and waist-to-hip ratio (WHR) for all-cause, cardiovascular, and cancer mortality. RESULTS: A total of 115,961 participants were included in the study. The results showed a U-shaped association between BMI and mortality, indicating that both males and females with BMIs of less than 21.0 kg/m2 and greater than or equal to 30.0 kg/m2 are at increased risk. The results showed that males with a BMI of less than 18.5 kg/m² had a significantly higher risk of all-cause mortality (adjusted hazard ratio [aHR], 2.24; 95% CI, 1.73 to 2.91) and cardiovascular mortality (aHR, 2.27; 95% CI, 1.23 to 4.20). Similarly, males with a WHR of less than 0.80 (aHR, 1.38; 95% CI, 1.08 to 1.77), 0.90 to less than 0.95 (aHR, 1.15; 95% CI, 1.02 to 1.29), and greater than or equal to 0.95 (aHR, 1.28; 95% CI, 1.11 to 1.47) showed an increased risk of all-cause mortality. In females, a BMI of less than 18.0 kg/m2 was linked to a higher risk of cardiovascular mortality (aHR, 2.67; 95% CI, 1.13 to 6.33). CONCLUSIONS Being underweight was associated with an increased risk of mortality in both sexes, and the lowest risk of death was found in males who were slightly overweight with a BMI of 23.0-25.0 kg/m2.

OBJECTIVES: We aimed to assess the impact of obesity on mortality in middle-aged Koreans using data from a Health Examinees study. METHODS: We used data from the participants who had complete information on body size and gave informed consent for the linkage of their data with the national death certificate data. Cox proportional hazard model was used to estimate the hazard ratios and 95% confidence intervals (CIs) of body mass index (BMI) and waist-to-hip ratio (WHR) for all-cause, cardiovascular, and cancer mortality. RESULTS: A total of 115,961 participants were included in the study. The results showed a U-shaped association between BMI and mortality, indicating that both males and females with BMIs of less than 21.0 kg/m2 and greater than or equal to 30.0 kg/m2 are at increased risk. The results showed that males with a BMI of less than 18.5 kg/m² had a significantly higher risk of all-cause mortality (adjusted hazard ratio [aHR], 2.24; 95% CI, 1.73 to 2.91) and cardiovascular mortality (aHR, 2.27; 95% CI, 1.23 to 4.20). Similarly, males with a WHR of less than 0.80 (aHR, 1.38; 95% CI, 1.08 to 1.77), 0.90 to less than 0.95 (aHR, 1.15; 95% CI, 1.02 to 1.29), and greater than or equal to 0.95 (aHR, 1.28; 95% CI, 1.11 to 1.47) showed an increased risk of all-cause mortality. In females, a BMI of less than 18.0 kg/m2 was linked to a higher risk of cardiovascular mortality (aHR, 2.67; 95% CI, 1.13 to 6.33). CONCLUSIONS Being underweight was associated with an increased risk of mortality in both sexes, and the lowest risk of death was found in males who were slightly overweight with a BMI of 23.0-25.0 kg/m2.

OBJECTIVES: We aimed to assess the impact of obesity on mortality in middle-aged Koreans using data from a Health Examinees study. METHODS: We used data from the participants who had complete information on body size and gave informed consent for the linkage of their data with the national death certificate data. Cox proportional hazard model was used to estimate the hazard ratios and 95% confidence intervals (CIs) of body mass index (BMI) and waist-to-hip ratio (WHR) for all-cause, cardiovascular, and cancer mortality. RESULTS: A total of 115,961 participants were included in the study. The results showed a U-shaped association between BMI and mortality, indicating that both males and females with BMIs of less than 21.0 kg/m2 and greater than or equal to 30.0 kg/m2 are at increased risk. The results showed that males with a BMI of less than 18.5 kg/m² had a significantly higher risk of all-cause mortality (adjusted hazard ratio [aHR], 2.24; 95% CI, 1.73 to 2.91) and cardiovascular mortality (aHR, 2.27; 95% CI, 1.23 to 4.20). Similarly, males with a WHR of less than 0.80 (aHR, 1.38; 95% CI, 1.08 to 1.77), 0.90 to less than 0.95 (aHR, 1.15; 95% CI, 1.02 to 1.29), and greater than or equal to 0.95 (aHR, 1.28; 95% CI, 1.11 to 1.47) showed an increased risk of all-cause mortality. In females, a BMI of less than 18.0 kg/m2 was linked to a higher risk of cardiovascular mortality (aHR, 2.67; 95% CI, 1.13 to 6.33). CONCLUSIONS Being underweight was associated with an increased risk of mortality in both sexes, and the lowest risk of death was found in males who were slightly overweight with a BMI of 23.0-25.0 kg/m2.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. Methods: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. Results: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. Conclusion This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Background: The anti-oxidative, anti-inflammatory, and anti-apoptotic effects of erythropoietin may provide neuroprotective effects. Erythropoietin also modulates autophagy signaling that may play a role in anesthesia-induced neurotoxicity (AIN). Herein, we investigated whether AIN can be attenuated by the neuroprotective effect of erythropoietin in the Caenorhabditis elegans (C. elegans). Methods: Synchronized worms were divided into the control, Iso, EPO, and EPO-Iso groups. The chemotaxis index (CI) was evaluated when they reached the young adult stage. The lgg-1::GFP-positive puncta per seam cell were used to determine the autophagic events. The erythropoietin-mediated pathway of autophagy was determined by measuring the genetic expression level of let-363, bec-1, atg-7, atg-5, and lgg-3. Results: Increased lgg-1::GFP puncta were observed in the Iso, EPO, and EPO-Iso groups. In the Iso group, only the let-363 level decreased significantly as compared to that in the control group (P = 0.009). bec-1 (P < 0.001), atg-5 (P = 0.012), and lgg-3 (P < 0.001) were expressed significantly more in the EPO-Iso group than in the Iso groups. Repeated isoflurane exposure during development decreased the CI. Erythropoietin could restore the decreased CI by isoflurane significantly in the EPO-Iso group. Conclusions Erythropoietin showed neuroprotective effects against AIN and modulated the autophagic pathway in C. elegans. This experimental evidence of erythropoietin-related neuroprotection against AIN may be correlated with the induced autophagic degradation process that was sufficient for handling enhanced autophagy induction in erythropoietin-treated worms.

Rare diseases are predominantly genetic or inherited, and patients with these conditions frequently exhibit neurological symptoms. Diagnosing and treating many rare diseases is a complex challenge, and their low prevalence complicates the performance of research, which in turn hinders the advancement of therapeutic options. One strategy to address this issue is the creation of national or international registries for rare diseases, which can help researchers monitor and investigate their natural progression. In the Republic of Korea, we established a registry across 5 centers that focuses on 3 rare diseases, all of which are characterized by gait disturbances resulting from motor system dysfunction. The registry will collect clinical information and human bioresources from patients with amyotrophic lateral sclerosis, spinocerebellar ataxia, and hereditary spastic paraplegia. These resources will be stored at ICreaT and the National Biobank of Korea. Once the registry is complete, the data will be made publicly available for further research. Through this registry, our research team is dedicated to identifying genetic variants that are specific to Korean patients, uncovering biomarkers that show a strong correlation with clinical symptoms, and leveraging this information for early diagnosis and the development of treatments.