Purpose: While the benefit of neoadjuvant chemotherapy (NAC) has been established in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers, its effectiveness in achieving pathological complete response (pCR) and optimal patient selection in estrogen receptor (ER)-positive, HER2-negative breast cancers remain less clearly defined. This study aimed to identify immunohistochemistry (IHC)-based predictors of pCR and to develop a scoring model for ER-strong positive/HER2-negative breast cancer. Methods: Data from a prospective cohort were retrospectively analyzed. We included 522 patients with ER-strong positive/HER2-negative tumors who received NAC and surgery between 2008 and 2021. IHC markers including progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and p53 were evaluated to identify predictors of pCR. Independent predictors of pCR from multivariate logistic regression were used to develop a weighted 4-point model. Model performance was assessed using receiver operating characteristic analysis. The prognostic impact of pCR was evaluated using KaplanMeier and Cox regression analyses. Results: Independent predictors of pCR included PR-negative status, positivity for basallike markers (EGFR or CK5/6), and Ki-67 ≥ 50%. The scoring model demonstrated good discrimination for pCR (area under the curve = 0.754). pCR rates increased stepwise, with scores of 4.9% (low), 10.7% (intermediate), and 36.2% (high). In the high-score group, pCR was significantly associated with improved disease-free survival (hazard ratio [HR], 0.09; p = 0.023) and distant metastasis-free survival (HR, 0.11; p = 0.035), whereas no significant survival differences according to pCR status were observed in the low and intermediate score groups. Conclusion This IHC-based model predicts pCR and helps identify subgroups in which pCR is associated with meaningful survival benefit following NAC in ER-positive/HER2-negative breast cancers. High-scoring patients may benefit from NAC, while patients with low- or intermediatescores may be better managed with surgery and endocrine therapy. This model may support personalized treatment decisions regarding NAC.

Purpose: Triple-negative breast cancer (TNBC) is a frequent phenotype of BRCA-mutanttumors. Tumors with BRCAness may show characteristics of BRCA-mutant tumors and respond to similar treatments. Next-generation sequencing is an efficient and cost-effective method for simultaneously sequencing multiple cancer susceptibility genes, surpassing conventional Sanger testing. Methods: A total of 148 women with TNBC were recruited from December 2015 to November 2018, as part of a sub-analysis based on the PEARLY trial data. Of them, 103 patients received neoadjuvant chemotherapy (NCT). The targeted genes related to hereditary cancers were sequenced using the 65-gene germline next-generation sequencing (gNGS) panel pathogenic and likely pathogenic variants (P&LPs) were determined by Sanger sequencing. We examined the occurrence of pathologic complete remission (ypCR) in patients with P&LPs. Results: The patients’ median age was 47 years (range, 27–69 years). Twenty (13.7%) of 148 patients had P&LP in six genes, including BARD1 (n = 2), BRCA1 (n = 9), BRCA2 (n = 5), CHEK2 (n = 1), RAD51C (n = 1), and RAD51D (n = 2). Among the 103 patients with NCT, 43 (41.7%) achieved ypCR (P&LPs; 9 individuals vs. non-variants; 34 individuals). Among the 103 patients with NCT, 14 (9.3%) had P&LPs. Nine of 14 patients with P&LPs, including BARD1 (n = 2), BRCA1 (n = 4), BRCA2 (n = 1), RAD51C (n = 1), and RAD51D (n = 1), achieved ypCR, showing a trend toward statistical significance (p = 0.066). Conclusion Germline P&LP mutations in TNBC patients can be detected by gNGS. This panel test can identify BRCA and BRCAness mutations that may predict ypCR in TNBC.

Purpose: Based on the KEYNOTE-522 study, neoadjuvant pembrolizumab plus chemotherapy has become the standard treatment for early-stage triple-negative breast cancer (TNBC).This study evaluated the real-world efficacy, safety, and predictors of pathologic complete response (pCR) in Korean patients. Methods: We conducted a retrospective cohort study of 174 patients with early-stage TNBC who received the KEYNOTE-522 regimen (neoadjuvant pembrolizumab plus paclitaxel and carboplatin, followed by doxorubicin and cyclophosphamide) at a tertiary cancer center between August 2022 and July 2024. We assessed the primary endpoints, including pCR rate and event-free survival (EFS). We performed univariable and multivariable logistic regression analyses to identify independent predictors of pCR. Results: The median patient age was 50 years (range, 24–74 years). The clinical stages were II and III in 79.3% and 20.1% of patients, respectively, and 10.9% had clinical N3 disease. The overall pCR rate was 62.1%, and the N3 subgroup had a pCR rate of 47.4%. On multivariable analysis, high baseline Ki-67 expression (≥ median, 75%) was significantly associated with pCR (odds ratio, 2.84; 95% confidence interval, 1.45 to 5.66; p = 0.002). At a median followup of 18.4 months, the 12-month EFS rate was 97.4%, with significantly superior outcomes observed in patients who achieved pCR compared with those who did not achieve pCR (100% vs. 93.1%, p = 0.007). The treatment completion rate was 92.0%, and immune-related adverse events occurred in 13.8% of patients. Conclusion In this real-world analysis of one of the largest Asian cohorts of patients with earlystage TNBC treated with neoadjuvant pembrolizumab, the KEYNOTE-522 regimen demonstrated substantial efficacy and manageable toxicity, consistent with the original trial findings.

Purpose: Lobular carcinoma In Situ (LCIS) is a noninvasive lesion associated with an increased risk of invasive cancer. Since its removal from the tumor, node, metastasis classification in the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines, the clinical management of LCIS has shifted from surgery to surveillance. However, studies focusing on the risk and associated factors for invasive cancer development in pure LCIS without ductal carcinoma In Situ (DCIS) or invasive cancer remain limited. Methods: We retrospectively analyzed 106 patients diagnosed with pure LCIS between 2008 and 2018. This study evaluated the effect of tamoxifen use and histologic type on the development of invasive cancer. Results: All 106 patients underwent surgery, and nine (8.5%) developed invasive cancer over a median follow-up of 67.5 months. The incidence of invasive cancer was lower in the tamoxifen group (6.3%, n = 4) than in the non-tamoxifen group (11.9%, n = 5), although this difference was not statistically significant (p = 0.266). Pleomorphic LCIS had a significantly higher incidence of invasive cancer (30.0%, n = 3) than classic LCIS (6.3%, n = 6) (p = 0.045).Multivariable Cox regression analysis showed no significant difference in the risk of invasive cancer according to tamoxifen use (hazard ratio [HR], 2.031; 95% confidence interval [CI], 0.544–7.579; p = 0.292). However, pleomorphic LCIS showed a trend toward an increased risk of invasive cancer compared to classic LCIS (HR, 3.856; 95% CI, 0.922–16.126; p = 0.064). Conclusion Postoperative tamoxifen did not significantly lower invasive cancer development in patients with pure LCIS. Pleomorphic LCIS may carry a higher risk than classic LCIS. These findings require tailored follow-up and treatment strategies based on the histologic subtype of LCIS.

Reference management software (RMS) represents a cornerstone of modern academic writing and publishing. For decades, programs such as EndNote, Zotero, and Mendeley have played central roles in facilitating citation organization, bibliography formatting, and collaborative scholarship. Although each platform has introduced unique innovations, persistent limitations remain, particularly with respect to usability, accessibility, and accuracy. In parallel, the rise of generative artificial intelligence has introduced an unprecedented challenge: the inadvertent inclusion of fabricated or incorrect references mistakenly incorporated into manuscripts. This phenomenon has exposed a critical limitation of traditional RMS platforms, namely their inability to verify reference authenticity. Against this backdrop, new solutions have emerged. One such example is CiteWell (https://citewell.org/), an artificial intelligence (AI)-era RMS that introduces several notable innovations, including PubMed-integrated verification, an intuitive interface for new users, customizable journal-specific styles, and multilingual accessibility. This review provides a comprehensive historical overview of RMS, evaluates the strengths and weaknesses of major platforms, and positions emerging AI-based tools as a new paradigm that combines traditional reference management with essential safeguards for contemporary academic challenges.

Purpose: Declines in masticatory function have been reported to be closely associated with cognitive impairment and reduced brain activity in older adults. This study aimed to investigate the effects of intraoral vibratory stimulation on masticatory function, cognitive performance, and brain activity in elderly individuals and to evaluate its potential efficacy. Materials and Methods: Participants were divided into a vibration-stimulation group (n=9) and a non-vibration control group (n=7). Baseline assessments were conducted at the first visit. Participants then received either vibratory stimulation or a wash-out (control) condition for two weeks, followed by the same assessments at the final visit. Evaluation measures were dental assessments (maximum bite force, masticatory performance, and salivary flow rate), cognitive tests (CANTAB, paper-based and computerized tests), quantitative electroencephalography (qEEG), and functional magnetic resonance imaging (fMRI) during a short-term memory task. Results: No significant long-term effects or statistically meaningful differences were observed between the two groups in cognitive performance or brain activity. Similarly, no pre- to post-intervention differences were found between groups in dental measures related to masticatory function (maximum bite force, masticatory performance, and salivary flow rate). Due to the limited sample size, this study functioned as a pilot study focusing on descriptive rather than inferential statistical analysis. Conclusion Intraoral vibratory stimulation did not demonstrate immediate or clear effects on cognitive function or brain activity in older adults, suggesting the need for optimization of stimulation parameters such as location and intensity. Future studies with larger sample sizes and improved stimulation methods replicating masticatory function are warranted to further explore the potential cognitive benefits.

The efficacy of clarithromycin-containing triple therapy (TT) against Helicobacter pylori has declined in Korea, with recent first-line eradication rates falling below 70%. Clarithromycin resistance exceeded 30%, undermining the standard regimen for H. pylori. These trends necessitate a change in the treatment strategy. This review analyzed the shift proposed in the draft of the 2025 Korean H. pylori guidelines. We examined the rationale for abandoning TT as a first-line empirical therapy and the establishment of a new dual-pillar strategy: 1) the declining role of clarithromycin-containing TT as a first-line treatment and 2) polymerase chain reaction (PCR)-based tailored therapy as the recommended precision approach. We explored the 1) emergence of new empirical regimen options, 2) application of tailored therapy, and 3) adoption of potassium-competitive acid blockers (P-CABs). Empirical regimens have shifted toward four-drug combinations to achieve higher cure rates. Concomitant therapy (proton-pump inhibitor [PPI] or P-CAB+amoxicillin+clarithromycin+metronidazole) offers high efficacy but raises concerns about antibiotic overuse. As a compromise, bismuth-augmented triple regimens (adding bismuth to TT) are now recommended; these modified quadruple therapies (e.g., PACB: PPI+amoxicillin+clarithromycin+bismuth, or PAMB: PPI+amoxicillin+metronidazole+bismuth) significantly improve eradication rates without requiring a third antibiotic class. Regarding tailored therapy, PCR-based domestic clinical research data consistently achieves ≥90% cure rates in first-line treatment—markedly higher than empirical TT in Korea. Economic analyses supported the cost-effectiveness of this approach. The guideline algorithm for salvage therapy was clarified. Bismuth quadruple therapy has been confirmed as the standard second-line treatment. For third-line therapy, we analyzed the efficacy of levofloxacin-based regimens, rifabutin-based therapy, and bismuth add-on therapy with two previously unused antibiotics. The 2025 Korean guidelines establish quadruple therapies as the new standard through a dual strategy: pragmatic empirical treatment and PCR-guided tailored therapy, with P-CABs and bismuth-based regimens as key components.

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.

Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Purpose: Esophagojejunal anastomotic leakage (EJAL) represents a severe postoperative complication following total or proximal gastrectomy. Treatment strategies include conservative management, endoscopic interventions, and surgery; however, comparative data remain limited. This study aimed to compare clinical outcomes of different strategies to identify the optimal approach based on anastomotic defect size. Materials and Methods: This retrospective study reviewed 100 patients diagnosed with EJAL between January 2015 and October 2024. Patients were categorized into four groups:conservative management, endoscopic vacuum-assisted closure (E-VAC), other endoscopic treatments, and surgery. The primary outcomes were leakage duration and length of hospital stay after EJAL diagnosis, whereas the secondary outcome was time to C-reactive protein normalization. Subgroup analyses were performed according to defect size. Results: Among the 100 patients, 76 were male and 24 were female, with a mean age of 65.7 years. Conservative treatment was the most common modality (53%), followed by other endoscopic treatments (19%), E-VAC (14%), and surgery (14%). In patients with a defect size <1 cm, conservative treatment was associated with significantly shorter leakage duration (P=0.035) and earlier resumption of diet (P=0.029) compared with endoscopic treatment.Among those with defects ≥2 cm, E-VAC demonstrated the most favorable median outcomes across all variables; however, statistical significance was not achieved because of the small sample size. Conclusions Conservative treatment appears to be the most effective treatment strategy for EJAL with anastomotic defects <1 cm. For larger defects (≥2 cm), E-VAC may offer clinical benefit, although further studies are needed to confirm its efficacy. These findings highlight the importance of individualized treatment selection based on defect size.