The recent approval of trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancer mandates an adequate assessment of these categories. Methods: Seven breast pathologists from the Breast Pathology Study Group of the Korean Society of Pathologists held an on-site expert consensus meeting. Fifteen sets of virtual whole slide images (WSI) of hematoxylin and eosin stain and HER2 immunohistochemistry were provided. The pathologists were given 60 minutes to submit their diagnosis of HER2 expression into null, ultralow, 1+, 2+, or 3+. Afterwards, in-depth discussion and consensus diagnoses were made by real-time visualization of the WSI. Results: After the consensus meeting, unanimous 100% agreements were seen only in five (33.3%) of the examined cases, which consisted of three 1+ cases and two 2+ cases. Two cases (13.3%) had mild disagreement, with only one pathologist’s disagreement. Of note, eight cases (53.3%) showed significant disagreement, defined by more than two pathologists’ disagreement. All HER2-null cases were reclassified as ultralow after consensus review, suggesting potential widespread underclassification of ultralow cases in clinical practice. Conclusions: Experts had significant discrepancies in interpreting HER2-low/ultralow status. It is important to assess if the distinction between HER2-low and ultralow is strictly required and if HER2-null breast cancer exists in reality.

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: Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets. Materials and Methods: Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM. Results: Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D. Conclusion This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.

Background and Objectives: Hearing loss significantly affects communication, psychosocial well-being, and quality of life. This study analyzes the National Health Insurance Service database to assess the trends and characteristics of hearing loss in South Korea from 2010 to 2020.Subjects and Method The database encompasses 97% of the Korean population, providing comprehensive data on medical history, prescriptions, and health examinations. The analysis used the World Health Organization’s ICD-10 definitions to categorize hearing loss types and examine their prevalence and incidence across various demographics over 11 years. Results: There was an overall annual increase of 4.62% in diagnosed cases of hearing loss, with the most significant rise among the elderly. The rate of increase accelerated from 3.32% between 2010 and 2014 to 6.49% between 2014 and 2020, corresponding with the improved hearing aid access facilitated by policy changes. Women showed a slightly higher increase than men. The data also indicated a consistent rise in abnormal hearing test results during health examinations, especially in older adults. Conclusion The study highlights an increasing trend in hearing loss diagnoses, driven by an aging population and enhanced detection facilitated by policy changes. These findings emphasize the need for continuous monitoring and targeted health policies to manage hearing loss effectively, offering valuable insights for global health management and policy development.

Background and Objectives: This study aims to analyze trends in hearing disability and the use of hearing rehabilitation devices (hearing aids and cochlear implants) in South Korea over the past 11 years (2010-2020) using data from the National Health Insurance Service (NHIS).Subjects and Method Data were extracted from the NHIS database, covering approximately 97% of the South Korean population. Patients diagnosed with hearing loss were classified using ICD-10 codes. The data were analyzed to determine trends in hearing disability, hearing aid prescriptions, and cochlear implant usage by age, gender, and types and causes of hearing loss. Results: The number of hearing disability patients increased from 170900 in 2010 to 362738 in 2020, with an annual growth rate of 7.95%. The highest increase was observed in the ≥60 age group, with an annual growth rate of 11.04%. Hearing aid prescriptions rose from 4966 in 2010 to 11974 in 2020, showing a 10.45% annual increase. Females showed a higher growth rate in both hearing disability and hearing aid prescriptions compared to males. Cochlear implant prescriptions also increased, particularly among older adults. Conclusion The study highlights a significant rise in hearing disability and the use of hearing aids and cochlear implants in South Korea, especially among the elderly. The findings underscore the importance of early diagnosis and intervention for hearing loss and the need for policy improvements to enhance accessibility and affordability of hearing rehabilitation services. Additional strategies are needed to ensure appropriate hearing rehabilitation for those not yet receiving adequate care.

Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44–1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67–1.14; p=0.310). Conclusions Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44–1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67–1.14; p=0.310). Conclusions Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.