Background and Objectives: This study was performed to comprehensively examine the amplitudes of the binaural interaction components (BICs) elicited by chirps, clicks, and 500 Hz tone-burst stimuli in individuals with normal hearing. Electrophysiological evidence of BICs was obtained and assessed for correlations with interaural time difference (ITD) and interaural level difference (ILD). Subjects and Methods: Sixteen adults (4 males and 12 females) with normal hearing participated in this study. Auditory brainstem responses (ABRs) to chirp, click, and 500 Hz tone-burst stimuli were recorded, and BICs were derived based on wave V. The behavioral thresholds of ITDs and ILDs across multiple frequencies were obtained and analyzed. Results: BICs were found in most participants, regardless of stimulus type. The amplitudes of BICs elicited by chirps were the highest, followed by those elicited by clicks and 500 Hz tone-bursts. A significant correlation was found between the amplitudes of chirp-evoked BICs and the thresholds of 500 Hz ITDs and ILDs. Conclusions This study found that chirp stimuli may be effective in eliciting BIC and predicting behavioral binaural interaction processing at low frequencies.

Purpose: Breast cancer gene (BRCA) mutation is a well-known risk factor for breast cancer, and clinical interest in prophylactic mastectomy has increased in recent years.We investigated patients who were BRCA mutation carriers and underwent contralateral risk-reducing mastectomy (RRM), focusing on the incidence of occult malignancy after contralateral RRM. Methods: Prospectively collected data of patients with breast cancer treated at a single institution were retrospectively reviewed. Patients who underwent RRM with BRCA mutation who underwent RRM between January 2010 and November 2023 were included in this study.Among patients who underwent contralateral RRM, those with a primary cancer diagnosis were included, and those with occult malignancy on the contralateral RRM side were reviewed additionally. The demographics and pathologies of both primary breast cancer and occult malignancies were evaluated. Results: In our institution, 925 patients were identified as BRCA mutation carriers, and 320 patients underwent contralateral RRM along with primary breast cancer surgery. BRCA2 mutation occurred more frequently (54.8%) in the overall BRCA mutation cohort. Furthermore, we reviewed 320 patients diagnosed with breast cancer and detected as BRCA mutation carriers who underwent contralateral RRM; high proportion of them were BRCA1 mutation carriers.Interestingly, we found a low incidence of only seven patients (2.2%) with occult malignancy on contralateral RRM side, which is different from that reported in other nations. Conclusion The incidence of occult malignancy in the contralateral breast of breast cancer patients with breast cancer with BRCA mutation is significantly low, and may be influenced by several factors. Increased utilization of screening and advancements in diagnostic technologies in South Korea have reduced the chance of occult malignancy in RRM, and a variety of pathologic examination methods may affect the rate of incidence.

Purpose: This study analyzed the pathological complete response (pCR) rates, long-term outcomes, and biological features of human epidermal growth factor receptor 2 (HER2)-zero, HER2-low, and HER2-positive breast cancer patients undergoing neoadjuvant treatment. Methods: This single-center study included 1,667 patients who underwent neoadjuvant chemotherapy from 2008 to 2014. Patients were categorized by HER2 status, and their clinicopathological characteristics, chemotherapy responses, and recurrence-free survival (RFS) rates were analyzed. Results: Patients with HER2-low tumors were more likely to be older (p = 0.081), have a lower histological grade (p < 0.001), and have hormone receptor (HorR)-positive tumors (p < 0.001). The HER2-positive group exhibited the highest pCR rate (23.3%), followed by the HER2-zero (15.5%) and HER2-low (10.9%) groups. However, the pCR rate did not differ between HER2-low and HER2-zero tumors in the HorR-positive or HorR-negative subgroups.The 5-year RFS rates increased in the following order: HER2-low, HER2-positive, and HER2-zero (80.0%, 77.5%, and 74.5%, respectively) (log-rank test p = 0.017). A significant survival difference between patients with HER2-low and HER2-zero tumors was only identified in HorR-negative tumors (5-year RFS for HER2-low, 74.5% vs. HER2-zero, 66.0%; log-rank test p-value = 0.04). Multivariate survival analysis revealed that achieving a pCR was the most significant factor associated with improved survival (hazard ratio [HR], 4.279; p < 0.001).Compared with HER2-zero, the HRs for HER2-low and HER2-positive tumors were 0.787 (p = 0.042) and 0.728 (p = 0.005), respectively. After excluding patients who received HER2-targeted therapy, patients with HER2-low tumors exhibited better RFS than those with HER2-zero (HR 0.784, p = 0.04), whereas those with HER2-positive tumors exhibited no significant difference compared with those with HER2-low tumors (HR, 0.975; p = 0.953). Conclusion Patients with HER2-low tumors had no significant difference in pCR rate compared to HER2-zero but showed better survival, especially in HorR-negative tumors.Further investigation into biological differences is warranted.

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 The risk factors for developing epilepsy following febrile convulsion (FC) have been studied extensively, but the underlying genetic components remain largely unexplored. Our objective here was to identify the risk loci related to FC through a genomewide association study of Korean epilepsy patients. Methods: We examined associations between a history of FC and single-nucleotide polymorphisms (SNPs) in data obtained from 125 patients with focal epilepsy: 28 with an FC history and 97 without an FC history. Results: Among 288,394 SNPs, 5 candidate SNPs showed p<1×10-4 . Regional association plots of these SNPs identified a novel locus adjacent to PROX1 that is implicated in hippocampal neurogenesis and epileptogenesis. The allele frequencies of the SNPs upstream of PROX1 including two candidate SNPs (rs1159179 and rs7554295 on chromosome 1) differed significantly between the groups with and without an FC history. In contrast, the allele frequencies of the SNPs inside PROX1 showed no differences, indicating dysregulated expression of PROX1 rather than a functional alteration in the PROX1 protein. Conclusions This novel discovery of SNPs upstream of PROX1 suggests that the dysregulated expression of PROX1 contributes to the development of focal epilepsy following FC. We propose that these SNPs are potential genetic markers for focal epilepsy following FC, and that PROX1 represents a potential therapeutic target of antiseizure medications.

Background: and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. Conclusions Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.

Purpose: Physical activity (PA) is considered a potentially effective factor in the primary prevention of gastric cancer (GC). As body mass index (BMI) and waist circumference (WC) differ by sex, particularly with age, this study aimed to investigate the impact of PA on GC development, considering BMI and WC variations by sex. Materials and Methods: We analyzed the impact of PA on GC development using Cox proportional hazard regression in a cohort of 314,525 Korean individuals from the National Health Insurance Service–Health Screening database, using data from 2009–2019.Additionally, subgroup analyses were conducted based on BMI and WC. The models were adjusted for age, sex, smoking status, alcohol consumption, BMI, and comorbidities. Results: The effect of PA on the prevention of GC development was relatively evident in males. The high PA group (metabolic equivalents of task, METs/week of 500–999) showed a lower risk of GC compared to the group with METs/week of 0 (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79–0.98). Especially in males with WC <90 cm and BMI <23 kg/m2 , a lower risk of GC was observed in the group with METs/week of 1–499 compared to the group with METs/week of 0 (HR, 0.80; 95% CI, 0.67–0.96). In contrast, no consistent association was observed between PA levels and risk of GC in females. Conclusions Moderate PA had a preventive effect on GC development in males, particularly in those with low BMI and WC. However, this effect was not observed in females.

Purpose: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal complication of gastric cancer (GC). This study aimed to evaluate the clinical characteristics, outcomes, and immunohistochemical profiles of patients with GC-induced PTTM. Materials and Methods: From 2011 to 2023, 8 patients were clinically diagnosed with PTTM associated with GC antemortem. Clinical features and outcomes were reviewed, and immunohistochemical staining for c-erbB-2, MutL protein homolog 1, and programmed cell death ligand-1 was performed. Results: The median patient age was 56 years (range, 34–66 years). In all the patients, the tumors exhibited either ulceroinfiltrative or diffusely infiltrative gross morphology.The median tumor size was 5.8 cm (range, 2.0 cm–15.0 cm). Poorly differentiated adenocarcinoma was the most common histological type (6/8, 75%), followed by signet ring cell carcinoma (1/8, 12.5%) and moderately differentiated adenocarcinoma (1/8, 12.5%).Chest computed tomography revealed ground-glass opacities (7/8, 87.5%) or tree-in-bud signs (2/8, 25.0%) without definite evidence of pulmonary thromboembolism. Disseminated intravascular coagulation was present in 62.5% (5/8) of the patients diagnosed with PTTM.C-erbB-2 was positive in one patient (1/8, 12.5%). One patient who received palliative chemotherapy after developing PTTM survived for 35 days, whereas the other 7 patients who did not receive chemotherapy after developing PTTM survived for 7 days or less after PTTM diagnosis. Conclusions Most patients with GC-induced PTTM had an undifferentiated-type histology, infiltrative morphology, and extremely poor survival. Palliative chemotherapy may benefit patients with GC-induced PTTM; however, further studies are needed to explore the potential of targeted therapy in these patients.