Probiotics have gained increasing clinical attention as adjunctive treatment for lower gastrointestinal disorders. However, evidence supporting their therapeutic efficacy remains limited, particularly with regard to sex-related differences. This expert review provides evidence-based insights and practical recommendations for the use of probiotics in patients with irritable bowel syndrome (IBS), functional constipation (FC), and Clostridioides difficile infection (CDI), considering possible sex-related differences. Evidence from randomized controlled trials and meta-analyses indicates that probiotics can modestly improve global symptoms, abdominal pain, and bloating in IBS and enhance bowel movement frequency and stool consistency in FC. However, these effects are strain-specific and heterogeneous. Although clinical studies on probiotics in IBS have not confirmed significant sex-related differences, experimental animal studies using stress-induced IBS models have demonstrated sex-dependent responses to specific probiotic strains, supporting the biological plausibility of such differences. For CDI, the efficacy of probiotics in preventing primary or recurrent infections remains inconsistent across large trials, and current guidelines usually do not recommend their routine use. However, sex- and age-related immunologic differences support the clinical differences of CDI. Probiotics are generally considered safe for healthy individuals, although caution is advised in patients who are immunocompromised or critically ill. Clinicians should select probiotic products based on strain-specific clinical evidence, adequate viable doses, patient characteristics and sex. In conclusion, probiotics might play a role as adjunctive therapy for IBS and FC, with variability in responses influenced by microbial, host, and potential sex-related factors. Further research is needed to establish optimized personalized probiotic strategies.

This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Purpose: We aimed to investigate how genetic predisposition to drinking and gastric cancer (GC) modifies the association between alcohol consumption and GC risk in the Korean population. Materials and Methods: Polygenic risk scores for GC (PRS-GC) and alcohol consumption (PRS-Alcohol) were formulated using genome-wide association results from BioBank Japan. Validation was performed using Korean cohorts (SNUBH-GENIE cohort), incorporating 8,846 controls and 531 patients with GC. Subsequently, these PRSs were applied to an independent Korean cohort of 67,771 participants, including 313 patients with GC during the follow-up for 14 years (KoGES cohort). Results: In KoGES cohort, the influence of alcohol consumption on GC risk was significantly altered by the PRS-GC and exhibited a synergistic interaction effect. PRS-Alcohol itself shows a negative correlation with GC risk. However, when actual alcohol consumption significantly exceeded genetically predicted levels, the risk of alcohol-related GC was notably increased (adjusted hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.72). Heavy drinkers in the high–PRS-GC/low–PRS-Alcohol group had a 2.16 times higher risk of GC than non-to-light drinkers, which was prominent in males. Conclusion Korean drinkers with higher PRS-GC who consume alcohol more than genetically predicted levels are susceptible to GC. PRS-GC and PRS-Alcohol may be beneficial for assessing the impact of alcohol consumption on GC risk in Koreans.

Purpose: We compared short-term clinical outcomes after cataract surgery with implantation of a novel refractive extended depth-of-focus TECNIS PureSee intraocular lens (IOL) between patients with stage 1 epiretinal membrane (ERM)—characterized by a thin membrane over the macula with preserved foveal depression―and those with a normal retina. Methods: This retrospective study included 60 eyes of 60 patients who underwent cataract surgery with implantation of the TECNIS PureSee IOL between January 2024 and January 2025: 30 eyes with stage 1 ERM and 30 eyes with a normal retina. Preoperative characteristics, including age, sex distribution, cataract severity, corrected distance visual acuity (CDVA), and higher-order aberrations, were compared between groups, as were IOL power and target refraction. Postoperative outcomes at 1 month―including CDVA, uncorrected distance, intermediate, and near visual acuity, ocular aberrations, and contrast sensitivity―were evaluated. Results: There were no significant differences in preoperative characteristics, such as age, sex distribution, cataract grade, CDVA, higher-order aberrations, IOL power, or target refraction between the two groups. At 1 month postoperatively, CDVA, uncorrected distance, intermediate, and near visual acuity, higher-order aberrations, and contrast sensitivity exhibited no significant differences between groups. Conclusions In this short-term analysis, the PureSee IOL demonstrated comparable efficacy and safety in cataract patients with stage 1 ERM to those with a normal retina.

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.

Purpose: Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research. Materials and Methods: Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes.Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes. Results: Data from 5,460 ESD cases from 5,250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days. Conclusions This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.

Purpose: This study aimed to develop and evaluate the effectiveness of the Trauma-nursing Education and Skill Support (TESS) program based on the ADDIE model (Analysis, Design, Development, Implementation, Evaluation model). The program was designed to enhance trauma nurses’ clinical competencies, including trauma-related knowledge, self-efficacy, and problem-solving ability, through the integration of theoretical education and simulation-based practice. Methods: A quasi-experimental study using a non-equivalent control group pretest–posttest design was conducted. Participants included 108 trauma nurses from regional trauma centers, military trauma centers, and emergency care facilities, who were assigned to an experimental group (n=52) or a control group (n=56). The TESS program consisted of a 2-day, 14-hour blended-learning course that included eight lecture sessions and four simulation-based practice stations. Data were collected at baseline, immediately after the intervention, and at 6 months using validated instruments measuring trauma-related knowledge, self-efficacy, and problem-solving ability. Two-way repeated-measures analysis of variance was used for data analysis. Results: The experimental group demonstrated significant improvements in trauma-related knowledge, self-efficacy, and problem-solving ability compared with baseline (all p<.001). These improvements were sustained at 6 months, although trauma-related knowledge scores showed a slight decline compared with immediate posttest levels. Between-group analyses confirmed significant group-by-time interaction effects for all outcomes: trauma-related knowledge (η2=0.12, p<.001), self-efficacy (η2=0.09, p=.002), and problem-solving ability (η2=0.08, p=.003). Conclusion The TESS program effectively enhanced trauma nurses’ trauma-related knowledge, self-efficacy, and problem-solving ability, with effects sustained for up to 6 months. Incorporating blended learning and simulation-based training into standardized trauma nursing education may strengthen clinical competencies and ultimately contribute to improved patient outcomes.

Probiotics have gained increasing clinical attention as adjunctive treatment for lower gastrointestinal disorders. However, evidence supporting their therapeutic efficacy remains limited, particularly with regard to sex-related differences. This expert review provides evidence-based insights and practical recommendations for the use of probiotics in patients with irritable bowel syndrome (IBS), functional constipation (FC), and Clostridioides difficile infection (CDI), considering possible sex-related differences. Evidence from randomized controlled trials and meta-analyses indicates that probiotics can modestly improve global symptoms, abdominal pain, and bloating in IBS and enhance bowel movement frequency and stool consistency in FC. However, these effects are strain-specific and heterogeneous. Although clinical studies on probiotics in IBS have not confirmed significant sex-related differences, experimental animal studies using stress-induced IBS models have demonstrated sex-dependent responses to specific probiotic strains, supporting the biological plausibility of such differences. For CDI, the efficacy of probiotics in preventing primary or recurrent infections remains inconsistent across large trials, and current guidelines usually do not recommend their routine use. However, sex and age difference of immunology supports the clinical differences of CDI. Probiotics are generally considered safe for healthy individuals, although caution is advised in patients who are immunocompromised or critically ill. Clinicians should select probiotic products based on strain-specific clinical evidence, adequate viable doses, patient's characteristics, or patient’s sex. In conclusion, probiotics might play a role as adjunctive therapy for IBS and FC, with variability in responses influenced by microbial, host, and potential sex-related factors. Further research is needed to establish optimized personalized probiotic strategies.

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.

Objective: To evaluate the diagnostic performance of the “probable hepatocellular carcinoma (HCC)” category in the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) v2022 guidelines. Materials and Methods: This multicenter retrospective study included patients at risk of HCC who underwent gadoxetic acid-enhanced MRI between January 2015 and June 2018; a subgroup of these patients also underwent liver CT. Eligible patients had at least one non-cystic lesion (≥10 mm) with a reference standard. Four radiologists interpreted the images independently and the results were pooled. The performance of “definite HCC” and “probable HCC” together and “probable HCC” alone were compared between v2018 and v2022. Results: A total of 2,237 patients (1,666 men; mean age, 59 ± 11 years) with 2,445 lesions were included. In v2022, 1.5% (143/9,780) of the lesions were additionally categorized as “probable HCC” by four reviewers on MRI; among these, 104 lesions were not HCCs. Focal nodular hyperplasia (FNH) or FNH-like nodules constituted 90.4% (94/104) of the false positives. When “definite HCC” and “probable HCC” were combined, v2022 showed higher sensitivity (83.7% [5,670/6,776] vs. 83.1% [5,631/6,776]) but lower specificity (77.1% [2,316/3,004] vs. 80.6% [2,420/3,004]) than v2018 (P < 0.001). For “probable HCC” alone, v2022 showed a lower positive predictive value (PPV) than v2018 (64.1% [373/582] vs. 76.1% [334/439], P < 0.001). In v2022, lesions with non-rim arterial-phase hyperenhancement (APHE) showed a lower PPV than those without APHE (42.3% [91/215] vs. 76.8% [282/367], P < 0.001). In the CT subgroup (n = 1,590), 1.6% (99/6,360) of the lesions were reassessed as “probable HCC,” and its PPV was 83.8% (83/99) in v2022 whereas no lesions were classified as “probable HCC” under v2018. Conclusion The revised “probable HCC” category in the KLCA-NCC v2022 aligns with updates in the diagnostic flow, demonstrating acceptable performance on MRI and CT. Notably, FNH or FNH-like nodules can be misclassified as “probable HCC” when MRI is used.