Background/Aims: This study investigated the clinical efficacy of low-dose mepolizumab (100 mg) in controlling severe eosinophilic asthma, aiming to induce eosinophilic granulomatosis with polyangiitis (EGPA) remission and reduce systemic steroid usage. Additionally, we constructed a basic frame for our longitudinal EGPA cohort by collecting serial blood samples before, during, and after mepolizumab treatment in EGPA patients. Methods: We conducted a 2-year prospective observational cohort study in patients with uncontrolled severe eosinophilic asthma and refractory EGPA who used systemic steroids (≥ 7.5 mg/day of prednisolone) or other immunosuppressant drugs for at least 6 months. All patients were treated with 100 mg of mepolizumab every 4 weeks for 1 year to control severe eosinophilic asthma and then were followed for an additional 1 year to monitor their disease course. We analyzed total systemic steroid use and EGPA remission/relapse during the study period. Results: Three EGPA patients were included in this study and completed 16 study visits over a 2-year period. After 1 year of treatment with mepolizumab (100 mg monthly), all 3 patients were able to reduce their maintenance dose of systemic steroids, with 2 patients completely discontinuing use. These 2 patients achieved EGPA remission during mepolizumab treatment, and their remission status remained stable for 1 year after they stopped receiving the medication. Conclusions Low-dose mepolizumab treatment demonstrated clinical efficacy in reducing the maintenance dose of systemic steroids required for severe refractory EGPA. While not all patients achieved EGPA remission with low-dose mepolizumab, some did, and their remission persisted even after treatment discontinuation.

Background: Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in children, with a rising incidence of macrolide resistance. Early diagnosis is crucial for reducing the disease burden; however, current diagnostic tools have limitations.We evaluated the diagnostic accuracy of serological assays and their performance based on symptom onset in children with CAP. Methods: From September 2023 to September 2024, we prospectively enrolled children with CAP, classified as M. pneumoniae pneumonia (MPP) or non-MPP, from 16 hospitals in Korea. Serological testing included chemiluminescence immunoassay (CLIA) and ELISA for detecting IgM and IgG, along with particle agglutination (PA) for total antibody measurements. Serological responses were analyzed at different times after symptom onset (0–4, 5–9, and 10–21 days). Results: Among 472 children with CAP (362 MPP, 110 non-MPP), 138 (29.2%) underwent PA testing, and 334 (70.8%) underwent IgM testing. PA at a 1:640 cutoff showed 48.0% sensitivity and 100% specificity. CLIA and ELISA showed comparable sensitivities (69.1% vs. 69.2%) and specificities (76.9% vs. 66.7%) for IgM testing. Seropositivity increased significantly with time since symptom onset (P for trend < 0.001), reaching 97.9% for IgM, 62.5% for IgG, and 94.7% for PA at 10–21 days. Conclusions The time post-symptom onset significantly influenced the diagnostic utility of serological tests for pediatric MPP, which showed limited value during the early stage of illness. These findings emphasize the importance of symptom onset-based interpretation of serological test results and their utility in complementing PCR when optimizing MPP diagnosis in children.

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 investigate whether breast tissue composition on preoperative automated breast ultrasound (ABUS) is associated with the accuracy of cancer multiplicity evaluation and postoperative recurrence-free survival (RFS) in patients with early-stage breast cancer. Materials and Methods: This retrospective analysis included women with early-stage breast cancer (clinical Tis, T1–2/N0) who underwent ABUS and digital mammography (DM) between October 2019 and April 2021. Tissue composition on ABUS was assessed using the Breast Imaging Reporting and Data System background echotexture (BE) (homogeneous-fat, homogeneous-fibroglandular, or heterogeneous). In a subgroup of patients with mammographically dense breasts, the glandular tissue component (GTC) on ABUS were further stratified into high (moderate or marked) or low (minimal or mild).Multivariable logistic and Cox regression analyses were used to identify factors associated with accurate cancer multiplicity categorization (unifocal, multifocal/multicentric, or bilateral) using ABUS + DM, and with RFS, respectively. Results: Among 409 women (mean age ± standard deviation, 50.2 ± 8.7 years), ABUS combined with DM yielded accurate cancer multiplicity categorization in 368 patients (90.0%). Neither BE nor GTC on ABUS affected the accuracy of categorization when ABUS was combined with DM. Over a median postoperative follow-up of 3.5 years, 11 recurrences occurred. Heterogeneous BE on ABUS (hazard ratio [HR] 11.24 [95% confidence interval [CI]: 2.82–44.92]; P = 0.001), BRCA mutation (HR 15.94 [2.47–102.97]; P = 0.004), and pathologic index cancer size (HR per 1-cm increase 1.91 [1.13–3.23];P = 0.02) was independently associated with RFS. In patients with dense breasts, heterogeneous BE (HR 14.17 [95% CI:2.69–74.60]; P = 0.002) and high GTC (HR 10.32 [2.35–45.28]; P = 0.002) on ABUS, BRCA mutation (HR 24.34 [2.75– 215.06]; P = 0.004), and pathologic cancer size (HR per 1-cm increase 2.62 [1.50–4.59]; P = 0.001) was independently associated with RFS. Conclusion In patients with early-stage breast cancer, heterogeneous BE and high GTC on preoperative ABUS, along with larger cancer size and BRCA mutation, was associated with worse RFS. However, BE and GTC did not affect cancer multiplicity evaluation when ABUS was used in combination with DM.

Objective: To evaluate the performance of supplemental automated breast ultrasound (ABUS) added to mammography-based breast cancer screening for women with nondense breasts. Materials and Methods: A retrospective search of radiology databases at two tertiary institutions identified asymptomatic women with nondense breasts who underwent breast cancer screening using both digital mammography (DM) and supplemental ABUS between January 2020 and December 2023. We excluded women without sufficient follow-up data or those without an established final diagnosis, including histopathologic results. The performance measures of DM alone and ABUS combined with DM (ABUS plus DM) were compared. The primary outcome was the cancer detection rate (CDR), and the secondary outcomes were sensitivity and specificity. Subgroup analyses were performed for women with scattered fibroglandular density and almost entirely fatty breasts. Results: A total of 2,904 pairs of screening examinations were performed in 1,683 women (59 ± 10 years), detecting 26 cancers. In comparison with DM alone, ABUS plus DM showed higher CDR (9.0 vs. 7.9 per 1,000 examinations, P < 0.001), higher sensitivity (100% [26/26] vs. 88.5% [23/26], P < 0.001), and lower specificity (95.0% [2,735/2,878] vs. 97.9% [2,817/2,878], P < 0.001). In women with scattered fibroglandular density, ABUS increased the CDR from 7.4 to 8.5 per 1,000 examinations and improved the sensitivity from 87.0% [20/23] to 100% [23/23] (P < 0.001). In women with almost entirely fatty breasts, ABUS plus DM showed the same CDR (16.4 per 1,000 examinations) and sensitivity (100% [3/3]) as DM alone. Three cancers (11.5% [3/26]), all of which were stage T1N0, were detected only by supplemental ABUS. Conclusion Supplemental ABUS improved cancer detection and sensitivity in women with nondense breasts, with the benefits primarily observed in those with scattered fibroglandular density.

Autophagy is a conserved catabolic process that degrades proteins and damaged organelles to maintain cellular homeostasis, and its role in cancer depends on stage and context. Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is an essential enzyme in the sterol branch of the mevalonate pathway, but its functions in hepatocellular carcinoma (HCC) and in the regulation of autophagy remain poorly understood. In this study, we show that FDFT1 acts as a negative regulator of autophagy in HCC cells. Loss of FDFT1 led to increased autophagosome formation and fusion with lysosomes, whereas its overexpression suppressed both basal and induced autophagy. These changes were associated with AMPK–ULK1 signaling, suggesting that FDFT1 influences a central pathway controlling autophagy. Our findings connect cholesterol metabolism with autophagy regulation and tumor growth, highlighting FDFT1 as a potential prognostic marker and therapeutic target in liver cancer.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC). Materials and Methods: This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models. Results: Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course. Conclusion Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.

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.