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.

The increasing detection of papillary thyroid microcarcinoma (PTMC) has raised concerns about overtreatment.For low-risk PTMC, either immediate surgery or active surveillance (AS) can be considered. To support AS implementation, the Korean Thyroid Association convened a multidisciplinary panel and developed the first Korean guideline. AS is recommended to adults with pathologically proven Bethesda V-VI PTMC without clinical evidence of lymph node or distant metastasis, gross extrathyroidal extension, tracheal or recurrent laryngeal nerve invasion, or aggressive histology. Baseline assessment requires high‑resolution cervical ultrasound by experienced operators to rule out extrathyroidal extension, tracheal or recurrent laryngeal nerve invasion, and lymph node metastasis;contrast‑enhanced neck computed tomography is optional. Patient characteristics such as age, comorbidities, and capacity for long-term follow-up should be assessed. Shared decision-making should weigh the benefits and risks of surgery and AS, expected oncologic outcomes, complications, quality of life, anxiety, medical cost, and patient preference. Follow-up includes cervical ultrasound and thyroid function test every six months for two years, then annually. Disease progression, defined as significant tumor growth or newly detected nodal or distant metastasis, warrants surgery. Despite remaining uncertainties, this guideline offers a framework to ensure oncologic safety and support patient-centered active surveillance.

This study was performed to evaluate the antibacterial activity of water-soluble mangostin derivatives (WsMD) of the ethanol extract of the peel of Garcinia mangostana L. (mangosteen) and the ethanol extracts of the fruit of Psoralea corylifolia L. and the root of Glycyrrhiza uralensis (licorice) against oral bacteria associated with endodontic infections. Cytotoxicity of the three natural products was tested on human embryonic kidney 293 cells (HEK 293) using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay or the cell counting method. Antimicrobial activity was evaluated based on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The highest concentrations of the WsMD of the ethanol extract of the peel of mangosteen and ethanol extracts of P. corylifolia L. fruit and licorice root without cytotoxic effects on HEK 293 cells were 20, 400, and 320 µg/ml, respectively. The MIC and MBC values of the WsMD of the ethanol extract of the peel of mangosteen and ethanol extracts of P. corylifolia L. fruit against 35 isolates (23 species) of pulpitis- and periapical disease-causative bacteria were 1.25–20 µg/ml and 25–200 µg/ml, respectively, except for Dialister invisus KCOM 1973. The ethanol extract of licorice root had MBC values of 40–320 µg/ml against 27 of 35 bacterial strains. These results showed that the WsMD of the ethanol extract of mangosteen peel had the highest antibacterial activity among the three natural extracts and suggested it as a potential root canal irrigation agent.

Purpose: Post-transplantation lymphoproliferative disorders (PTLDs) after hematopoietic stem transplantation (HCT) or solid organ transplantation (SOT) result in poorer outcomes, including death. There are limited large cohort data on the incidence and natural course of PTLD in Asians. Materials and Methods: We investigated PTLD using Korean national health insurance claims data of 47,518 patients who underwent HCT or SOT in 2008-2020. Patient demographics, time and type of PTLD diagnosis, type of PTLD treatment, and death data were collected. We used Fine and Gray subdistribution hazard models to calculate the cumulative incidence and risk factors for PTLD. Results: During median follow-up of 5.32 years, PTLD occurred in 294 of 36,945 SOT patients (0.79%) and 235 of 10,573 HCT patients (2.22%). Cumulative incidence of PTLD were 0.49% at 1 year, 1.02% at 5 years, and 1.50% at 10 years post-transplantation. Age < 20 years (subdistribution hazard ratio [SHR] of 1.67 in age 10-19, SHR 1.51 in age 0-9), HCT (SHR 3.02), heart transplantation (SHR 2.27), and liver transplantation (SHR 1.47) were significant risk factors for PTLD. The presence of PTLD was associated with an increased risk of death (hazard ratio of 2.84). Overall, 5-year survival of PTLD patients was 68.9% (95% confidence interval, 64.9 to 73.2). Conclusion We observed a steady increase in PTLD over 10 years after HCT or SOT in this large cohort study. Pediatric age group, HCT, liver transplantation, and heart transplantation were suggested to be risk factors for PTLD, and PTLD was associated with a higher risk of death.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

Purpose: Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer. Materials and Methods: We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment. Results: Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors. Conclusion Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.