Background: A novel botulinum toxin type A (Protoxin; Protox Inc.) has been developed. Objective: To evaluate the efficacy and safety of the newly developed Protoxin compared to the approved drug onabotulinumtoxinA (OBoNT) in moderate to severe glabellar lines. Methods: Adults with a glabellar line Facial Wrinkle Scale (FWS) score of 2 (moderate) or 3 (severe) were enrolled in the study. Subjects were randomized in a 1:1 ratio to receive either Protoxin or OBoNT. A total of 20 units of botulinum toxin was injected at five sites in the glabellar region (4 units at each site). FWS scores were assessed at baseline and at weeks 4, 8, 12, and 16 post-injection. The primary endpoint was the proportion of subjects at week 4 who had a reduction of 2 or more points in FWS and a final score of 0 (none) or 1 (mild). Results: A total of 274 subjects were randomized, of whom 78.1% were female. At week 4 post-treatment, the improvement rate of glabellar lines was 62.22% in the Protoxin group and 62.96% in the OBoNT group. The lower limit of the two-sided 95% confidence interval (−12.24%) exceeded the −15% margin, confirming the non-inferiority of the new drug. Safety profiles were comparable between the two groups. Conclusion Protoxin demonstrated efficacy and safety profiles comparable to those of OBoNT in the treatment of moderate to severe glabellar lines.

Gastroesophageal reflux disease (GERD) is a chronic and relapsing gastrointestinal disorder characterized by the reflux of gastric contents into the esophagus, leading to troublesome symptoms and/or complications. Since the publication of the 2020 Seoul Consensus on GERD, significant new evidence has emerged, particularly regarding acid-suppressive therapies and diagnostic approaches. This 2025 focused update aims to refine GERD management strategies by incorporating the latest evidence on acid suppressive therapies and regional considerations in Asian populations. This study builds on the 2020 Seoul Consensus by integrating systematic reviews, meta-analyses, and expert consensuses to offer updated recommendations for the definition and medical treatment of GERD. These guidelines incorporate recent advances in acid-suppressive therapies, particularly potassium-competitive acid blockers, and adopt updated diagnostic frameworks in accordance with the Lyon Consensus 2.0. Key clinical questions were identified and structured using the following format: Population, Intervention, Comparator, Outcome. The resulting recommendations address the initial treatment, long-term maintenance strategies, and role of personalized therapy based on disease severity, such as the grade of reflux esophagitis. Six key statements are presented: updated definition and classification of GERD (Statement 1); initial and long-term treatment strategies tailored to GERD phenotypes, such as non-erosive reflux disease, mild erosive esophagitis, and severe erosive esophagitis (Statements 2-5); and dose optimization strategies for long-term safety (Statement 6). These guidelines aim to support gastroenterologists and general healthcare providers in making individualized evidence-based decisions for GERD management.

This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

In forensic medicine, age estimation commonly involves assessing age-related changes in teeth and skeletal structures. Vertebral morphological alterations, such as osteophyte formation, serve as age indicators. Recent studies using deep-learning techniques, such as neural networks, for age estimation from radiographic images have been conducted, reporting significantly higher accuracy than previous studies. This study aimed to estimate age using neural network-based deep-learning techniques applied to computed tomography (CT) cross-sectional images of the spine and evaluate its feasibility. Postmortem CT scans of 214 cadavers with varying decomposition levels were used. Coronal and sagittal cross-sectional images penetrating the center of each vertebral body were extracted for the 11th and 12th thoracic vertebrae and the first to fifth lumbar vertebrae. Using these images, along with the chronological ages of deceased individuals, an age estimation model was developed through regression analysis in PyTorch, employing a convolutional neural networks architecture with five-fold cross-validation. The model achieved a mean absolute error of 5.385 years, root mean squared error of 7.029 years, and coefficient of determination of 0.793. Although the sample size was relatively small, the results suggested the potential applicability of vertebral imagingbased age estimation in the Korean population. Further research using a larger dataset may improve the accuracy and reliability of the model.

Purpose: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Purpose: Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant epidermal growth factor receptor (EGFR)–induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis. Materials and Methods: Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point. Results: We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as short chain fatty acid-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage. Conclusion Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Myofibromas are rare mesenchymal neoplasms that primarily affect infants and young children, most commonly arising in the skin, subcutaneous tissue, muscle, or bone. These tumors present with a broad clinical spectrum, ranging from self-limiting lesions to disseminated and fatal cases. In adults, the solitary form is encountered more frequently than the multicentric type. Although myofibromas may occur in the oral region of the head and neck, isolated cases involving the nasal septum are exceedingly rare. Here, we describe a case of solitary adult-onset myofibroma of the nasal septum that was successfully excised through transnasal endoscopic surgery.

Secondary rhabdoid tumors (RTs) with atypical teratoid/rhabdoid tumor-like features rarely arise from, or coexist with, pleomorphic xanthoastrocytomas (PXAs), and their clinicopathological and molecular characteristics remain poorly understood. We report a 17-year-old girl with a temporal lobe mass that, upon gross total resection, pathologically contained both RT and PXA components. Immunohistochemistry revealed loss of INI1 expression restricted to the RT component, while the PXA area retained INI1. Next-generation sequencing identified a shared BRAF::TRIM24 fusion and homozygous deletion of CDKN2A/2B in both components, indicating a shared clonal origin. Additionally, a germline ATM frameshift mutation (c.5288_5289insGA) was identified in both tumor components, making the first such report in central nervous system tumors. SMARCB1 loss was confined to the RT component, further supporting the hypotheses of clonal evolution and secondary transformation. Despite gross total resection, craniospinal irradiation, and chemotherapy, the patient developed rapid leptomeningeal dissemination and died 5 months after surgery. This case provides clinicopathological and molecular evidence for clonal evolution and secondary transformation of PXA into an RT. The presence of germline ATM mutation may have therapeutic and biological relevance. Further studies are required to clarify the pathogenesis and optimal management of these rare and aggressive tumors.

Sarcopenia is a progressive age-related musculoskeletal disorder characterized by loss of skeletal muscle mass, strength, and physical function. Closely associated with aging and physical inactivity, it significantly compromises mobility, independence, and quality of life in older adults. Exercise is widely recognized as an effective non-pharmacological intervention for managing sarcopenia. However, the underlying molecular mechanisms remain incompletely elucidated. Among the emerging mediators, exerkines, physical exercise-induced signaling molecules, are secreted by multiple tissues, including the skeletal muscle, bone, liver, and adipose tissue, and mediate the systemic beneficial impacts of exercise via autocrine, paracrine, and endocrine signaling. These factors play critical roles in interorgan communication, regulation of muscle regeneration, mitochondrial function, inflammation, and metabolic homeostasis. Importantly, the secretion profiles and biological functions of exerkines are modulated by exercise-specific parameters such as mode, intensity, and duration. Understanding the regulatory dynamics of exerkine signaling may offer novel therapeutic avenues, particularly for individuals unable to engage in regular physical activity. This review focuses on the recently identified exerkines relevant to skeletal muscle physiology and their implications in the pathophysiology of sarcopenia. We also provided a comprehensive overview of exerkine responses to various exercise modalities in the prevention and treatment of sarcopenia.