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.

Background: Intravenous (IV) fluid therapy is essential and widely used; however, it is associated with high error rates, largely due to human factors, necessitating constant and careful monitoring by medical staff. Gravity-based systems are prone to errors, whereas electronic pumps, though more accurate, are limited by size, cost, and complexity. In this study, the impact of single-drop weight measurement and real-time light source monitoring on the accuracy of gravity-based infusion systems was evaluated. Methods: Gravity-based IV sets with IV infusion flow regulators (IIFRs) from three manufacturers were tested using 1,000 ml of 0.9% saline. The drops per min and the drop weight were recorded using a pulse oximeter, which served as a light source. The flow rates from the pulse oximeter group (PO) were compared with those from the manufacturer’s drop volume (C) and the IIFR groups. The mean absolute percentage error (MAPE) of predicted versus actual volumes was analyzed along with correlations between the residual volume and drop rate. Results: The PO group values were statistically closer to those of the actual measurements than the C and IIFR groups values (P < 0.05), demonstrating higher accuracy and lower MAPE, except at 300 ml/h when than those of the C group, independent of residual volume. The residual volume strongly correlated with the drop rate (r > 0.9). Conclusions Real-time drop measurements using light sources combined with single-drop weight assessment improve the accuracy of these systems. Integrating pulse oximeters into IV sets may enhance clinical precision and reduce provider workload.

Objective: To assess whether performing exercises during hemodialysis reduces the risk of developing intradialytic hypotension and enhances exercise capacity in patients with chronic kidney disease. Methods: This study included patients aged ≥18 years undergoing hemodialysis. Participants performed exercises using a portable lower extremity ergometer during hemodialysis sessions for 3 weeks. Data regarding walking distance, knee strength, quality of life, fat-free mass, arterial pressure, blood pressure, heart rate, frequency of intradialytic hypotension, fatigue, and duration of hemodialysis were collected and analyzed. Results: Significant improvements in walking distance and knee strength were observed following the implementation of exercise training during hemodialysis. Although there was no significant reduction in the frequency of intradialytic hypotension, a decreasing trend was noted. Other parameters such as quality of life and fatigue did not show significant changes. Conclusion Using a portable ergometer during hemodialysis improved exercise capacity and knee strength in patients with chronic kidney disease. There was a trend toward reduced intradialytic hypotension, suggesting potential cardiovascular benefits. Further research with larger sample sizes is needed to confirm these findings.

Purpose: Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

Objectives: This study aimed to investigate the risk of osteoarthritis associated with menopausal hormone therapy (MHT). Methods: This population-based retrospective cohort study used a database of Korean health insurance claims (2007–2020). Females aged ≥ 40 who initiated menopause-related healthcare visits between 2011 and 2014 were identified. The MHT group comprised females aged ≥ 40 who initiated MHT for ≥ 6 months during this period. The non-MHT group comprised females aged ≥ 40 who attended menopause-related healthcare visits but did not receive MHT. To account for potential confounding factors, the two groups were matched at a 1:1 ratio using propensity score matching. Results: A cohort of 453,040 postmenopausal females aged ≥ 40 years was identified, with 26,354 assigned to either the MHT or nonMHT group after propensity matching. The median age was 49 years, and the median follow-up was 8.2 years. The Cox proportional hazards model demonstrated an elevated risk of osteoarthritis with MHT (hazard ratio [HR], 1.154; 95% confidence interval [CI], 1.117–1.193) for knee (HR, 1.148; 95% CI, 1.102–1.195) and other arthritis (HR, 1.205; 95% CI, 1.151–1.261), although not statistically significant for hip arthritis. Tibolone (HR, 1.211; 95% CI, 1.161–1.263), estrogen–progestogen therapy (EPT) (HR, 1.092; 95% CI, 1.048– 1.137), and estrogen therapy (ET) (HR, 1.235; 95% CI, 1.148–1.329) were associated with a higher risk of osteoarthritis compared to nonMHT users. Conclusions MHT was associated with an increased risk of osteoarthritis, consistently observed across tibolone, EPT, and ET, particularly affecting joints other than the hip, with a trend toward an elevated risk of hip osteoarthritis.

Objective: Easy-to-understand information on emergency patient transportation and emergency medical resources is required to operate emergency medical resources appropriately. This study evaluated emergency patient transport routes using a geographic information system (GIS) and converted them into visual information to understand the current status of emergency medical resource use in the region. Methods: The basic data used in this study were collected from the 119 safety centers in Gangwon-do, South Korea, under the fire-fighting headquarters in Gangwon-do from January 2017 to December 2020. The data were analyzed using the geographic information system and converted to visual information. Results: The number of patients with cardiovascular disease, cerebrovascular disease, and traffic accidents was 12,944. Of these, 9,393 patients (72.6%) were transported from Chuncheon city, and 3,551 patients (27.4%) were transported out of Chuncheon city. The number of patients with cardiovascular diseases during the study period was 1,219 (9.4%); 782 patients (64.2%) were transported to the K-EMC (emergency medical center), and 437 patients (35.8%) were transported to the H-EMC. For cerebrovascular disease, 913 patients (7.1%) were transported to the EMC of Chuncheon city, with 585 (64.1%) K-EMC and 328 (35.9%) H-EMC patients. The number of traffic accident patients was 1,266 (9.8%). Five hundred and forty (42.7%) and 726 (57.3%) patients were transported to the K-EMC and H-EMC, respectively. Conclusion The adequacy of facilities, equipment, and human resources required to treat cardiac and cerebrovascular diseases in K-EMC and severe trauma in H-EMC needs to be reviewed.

Duloxetine and thioctic acid (TA) are standard drugs for treating diabetic neuropathy, a primary complication associated with diabetes. In this study, ultra performance liquid chromatography coupled with tandem mass spectrometry methods was successfully developed and validated for quantifying duloxetine and TA in biological samples. The protein precipitation method was used to extract duloxetine, TA and their internal standards from beagle dog plasma. A Hypersil Gold C18 column (150 × 2.1 mm, 1.9 μm) was used for the experiment. Isocratic elution with 0.1% formic acid in acetonitrile (A) and 0.1% formic acid (B) was used for duloxetine, whereas a gradient elution with 0.03% acetic acid (A) and acetonitrile (B) was used for TA. The validated parameters included linearity, sensitivity, accuracy, precision, selectivity, matrix effect, stability, and recovery under different conditions. The linear ranges of the calibration curves for duloxetine and TA were 5–800 ng/mL and 5–1,000 ng/mL, respectively. An intra- and inter-run precision of ± 15% can be observed in all quality control samples. These methods were successfully used for pharmacokinetics (PKs) studies in beagle dogs to compare PK differences in a fixed-dose combination including duloxetine and TA and co-administration of the 2 drugs.

Purpose: Classical swine fever (CSF) reemerged on CSF-free Jeju Island where vaccination is not practiced by the unintentional injection of a live attenuated vaccine (modified live attenuated vaccines–low-virulence Miyagi [MLV-LOM]) in 2014. Since the Jeju provincial authority is considering adopting a voluntary immunization policy using a CSF-E2 subunit vaccine to combat LOM-derived CSF endemic, this study aimed to evaluate in Jeju herds. Materials and Methods: Two vaccination trials using the Bayovac CSF-E2 vaccine licensed for use in South Korea assessed the safety and humoral immunity of the CSF-E2 vaccine in breeding (trial 1) and nursery animals (trial 2) under farm application conditions. Results: Neither local nor systemic (including reproductive) adverse effects were objectively observed in pregnant sows and young piglets following a respective vaccination regime at pregnancy or weaning, respectively. Trial 1 showed that sows immunized with the CSF-E2 vaccine possessed high and consistent E2-specific and neutralizing antibody levels. The CSF-E2 vaccine-immunized pregnant sows subsequently conferred appropriate and steady passive immunity to their offspring. In trial 2, a double immunization scheme of the CSF-E2 vaccine in piglets at 40 and 60 days of age could elicit a consistent and long-lasting adequate antibody response. Additionally, the two trials detected no E rns -specific antibody responses, indicating that CSF-E2 vaccine can differentiate infected from vaccinated animals (DIVA). Conclusion Our trial data collectively provide invaluable information on applying the CSFE2 subunit vaccine to circumvent the possible drawbacks associated with the MLV-LOM concerning the safety, efficacy, and DIVA, in the LOM-endemic field farms and contribute to advanced CSF eradication on Jeju Island.