Microglial activation during aging is associated with neuroinflammation and cognitive impairment. Galectin-3 plays a crucial role in microglial activation and phagocytosis. However, the role of galectin-3 in the aged brain is not completely understood. In the present study, we investigated aging-related mechanisms and microglial galectin-3 expression in the mouse hippocampus using female 6-, 12-, and 24-month-old C57BL/6 mice. Western blot analysis revealed neurodegeneration, blood-brain barrier leakage, and increased levels of neuroinflammation-related proteins in 24-month-old mice compared to 6- and 12-month-old mice. Immunohistochemistry revealed an increase in activated microglia in the hippocampus of 24-month-old mice compared to 6- and 12-month-old mice. Furthermore, we found more galectin-3 and triggering receptor expressed on myeloid cells-2-positive microglia in 24-month-old mice compared to 6- and 12-month-old mice. Using primary mouse microglial cells, galectin -3 was also increased by lipopolysaccharide treatment. These findings suggest that galectin-3 may play an important role in microglial activation and neuroinflammation during brain aging.

Peyronie’s disease is an acquired condition characterized by penile deformities caused by fibrosis of the penile tunica albuginea, leading to symptoms such as penile pain, erectile dysfunction, and other associated issues. Despite extensive research, the pathophysiology of this condition remains poorly understood, and standardized diagnostic and treatment protocols are lacking. While clinical guidelines from several professional societies exist, they do not consistently account for factors such as patient ethnicity, geography, and socioeconomic status. Thus, the Korean Society for Sexual Medicine and Andrology (KSSMA) aimed to develop recommendations tailored to clinical practice in Korea. These recommendations summarize the latest evidence, including clinical practice guidelines from various international professional societies, and represent the consensus opinion of an expert group within the KSSMA. They encompass all aspects of Peyronie’s disease, including the definition, diagnosis, non-surgical interventions, and surgical treatment options.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Purpose: Cystic duct cancers (CDCs) have been classified as extrahepatic bile duct cancers or gallbladder cancers (GBCs); however, it is unclear whether their clinical behavior is similar to that of distal extrahepatic bile duct cancers (DBDCs) or GBCs. Materials and Methods: T category of the CDCs was classified using current T category scheme of the GBCs and DBDCs, and clinicopathological factors were compared among 38 CDCs, 345 GBCs, and 349 DBDCs. We modified Nakata’s classifications (type 1, confined within cystic duct [CD]; combined types 2-4, extension beyond CD) and compared them. Results: No significant overall survival (OS) difference was observed between the patients with CDC, GBC, and DBDC. The T category of GBC staging was more accurate at distinguishing OS in patients with CDC than the DBDC staging. Patients with T3 CDC and GBC showed a significant OS difference when using the T category for GBC staging, while those with T1-T2 CDC and GBC showed no significant difference. In contrast, the T category of DBDC staging did not show any significant OS difference between patients with T1-T2 CDC and DBDC or T3 CDC and DBDC. Patients with type 1 CDC had significantly better OS than those with combined types. Conclusion Unlike GBCs and DBDCs, CDCs exhibit distinct clinicopathological characteristics. The OS is better when the CDC confines within the CD, compared to when it extends beyond it. Therefore, we propose a new T category scheme (T1, confined to CD; T2, invaded beyond CD) for better classifying CDCs.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

Background: Long-term use of bisphosphonate is a risk factor for atypical femoral fractures (AFFs). Femoral bowing is known to be associated with AFFs. However, whether femoral bowing quickens the occurrence of AFF is unknown. The purpose of this study was to determine whether AFF occurs earlier in patients with severe femoral bowing than in those without severe bowing. Methods: One hundred and sixty-four patients (186 AFFs) from January 2006 to December 2022 were included in this study.According to severity of femoral bowing, patients were divided into 2 groups: severe bowing group (26 femurs) and minimal to moderate bowing group (160 femurs). Age, sex, and completeness and location of AFF were compared between the 2 groups. We compared the time of AFF occurrence after bisphosphonate therapy using cumulative percentage between the 2 groups. Results: Age and sex were similar between the 2 groups, while body mass index (BMI) was lower (22.5 ± 3.0 kg/m 2 vs. 24.5 ± 3.5 kg/m 2 , p = 0.003) in the severe bowing group. The duration of bisphosphonate use was shorter in the severe bowing group than in the minimal to moderate bowing group (3.3 ± 3.8 years vs. 5.0 ± 4.0 years, p = 0.048). In the severe bowing group, 85% of AFFs were diaphyseal in contrast to the 46% in the minimal to moderate bowing group (p < 0.001). Cumulative percentage plot of AFFs in the severe bowing group was left-shifted compared to the minimal to moderate bowing group. Conclusions At the time of AFF diagnosis, the severe bowing group exhibited shorter duration of bisphosphonate use, lower BMI, and a higher incidence of diaphyseal location. Shortening the duration of bisphosphonate therapy may be advisable in patients with severe femoral bowing.

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: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.