Background: Non-thermal atmospheric pressure plasma (NTAP) generates reactive oxygen species, reactive nitrogen species, and ultraviolet radiation, which can inactivate microorganisms.Onychomycosis treatment is challenging, and its prognosis is poor owing to mixed infections and dermatophytosis. Although NTAP has shown in vitro antifungal effects against dermatophytes and yeast, its efficacy against non-dermatophyte molds (NDMs) and in clinical or nail model studies remains poorly understood. Objective: We evaluated the effects of NTAP on fungi, including NDMs, and infected nail plates. Methods: For the in vitro experiments, Trichophyton rubrum, Candida albicans, Aspergillus fumigatus, and Fusarium oxysporum strains were exposed to NTAP. After NTAP exposure (2,4 and 6 minutes), growth curve, cell viability, and biofilm biomass were assessed by absorbance wavelength of 600 nm, XTT assay, and crystal violet staining, respectively. For the ex vivo experiments, infected nail plates were analyzed using a scanning electron microscope. Results: T. rubrum and C. albicans showed greater growth inhibition with increasing NTAP exposure time, whereas A. fumigatus showed enhanced growth after 6 minutes exposure. Many fungal elements within the subungual hyperkeratosis of the ex vivo specimen were all damaged following NTAP exposure. Conclusion NTAP has antifungal effects on dermatophytes, yeast, and NDMs. We suggest that the intensity and time of NTAP application should be adjusted according to each strain and can be more effective when NTAP directly reaches the hyphae on the nail bed or subungual hyperkeratosis.

The gastrointestinal stromal tumor (GIST) is one of the most common mesenchymal tumors of the gastrointestinal tract. Between the 1990s and early 2000s, GIST was identified as a tumor characterized by KIT or PDGFRA mutations, resulting in imatinib being established as an effective targeted therapy. However, with advances in molecular diagnostics, approximately 10%–15% of GISTs have been reported to harbor alternative mutations, such as those in the succinate dehydrogenase subunit genes and BRAF, leading to the development of additional targeted therapies. GISTs exhibit a wide spectrum of clinical behaviors, ranging from indolent to highly aggressive, prompting the development of diverse risk classification systems. However, multiple systems remain in use, leading to inconsistent pathologic reports. Moreover, the mitotic counting method—a key factor in risk stratification—has become a major source of confusion among pathologists owing to the adoption of digital pathology and discrepancies between updated international guidelines and outdated reimbursement requirements. These inconsistencies have hindered pathologic reporting and communication between pathologists and clinicians. This review comprehensively overviews the historical background, molecular subtypes, and risk classification systems of GIST, focusing on evolving issues in mitotic rate evaluation and the application of risk classification systems in clinical practice.

Purpose: We report two individual rare cases of the simultaneous occurrence of retinal and choroidal macrovessels.Case summary: The first case involved a 39-year-old male who presented with a two-week history of metamorphopsia in his right eye.At the initial visit, visual acuity was 1.0 in both eyes. A choroidal macrovessel transversing the macula was observed in the right eye, and a vascular loop in the inferior retinal arcade and a retinal macrovessel crossing the macula were identified in the left eye. Optical coherence tomography (OCT) revealed bilateral pachyvessels and subretinal fluid in the right macula, which persisted after two months. The second case involved a 36-year-old male with a six-month history of decreased vision in his left eye. At the initial visit, visual acuity was 0.1 in the right eye and 1.0 in the left eye. Subretinal fluid and retinal macrovessel were observed in the left macula. Two months later, the subretinal fluid resolved spontaneously. At a seven-year follow-up, OCT demonstrated pachyvessels in both eyes. Conclusions Although retinal and choroidal macrovessels originated from distinct embryologic vascular systems and are unlikely to share a direct developmental pathway, both cases showed bilateral pachyvessels. Dysregulation of vascular signaling factors such as vascular endothelial growth factor and angiopoietin, which are involved in both retinal and choroidal vascular development, may contribute to the formation of these abnormal macrovessel structures.

Objective: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy (ET) constitute the standard systemic treatment for estrogen receptor-positive, human epidermal growth factor 2-negative (ER+/HER2-) metastatic breast cancer (MBC). However, treatment responses remain heterogeneous, highlighting the need for reliable prognostic markers. This study aimed to evaluate the prognostic significance of 18F-fluorodeoxyglucose (FDG) PET/CT findings in this setting. Materials and Methods: This retrospective single-center cohort study included patients with ER+/HER2- MBC who underwent18F-FDG PET/CT before initiating CDK4/6 inhibitors plus ET between 2018 and 2023. Maximum standardized uptake value(SUVmax), whole-body metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. Progression-free survival (PFS) and overall survival (OS) were evaluated as the primary and secondary outcomes, respectively, using multivariable Cox models. PET parameters (SUVmax, MTV, and TLG) were analyzed as both continuous and dichotomized variables based on median values, adjusting for relevant clinical covariates. Results: Among the 374 patients, 82 (21.9%) presented with de novo metastatic disease, and 357 (95.5%) received CDK4/6 inhibitors as first-line therapy. In multivariable Cox analysis, all continuous PET parameters were independently associated with PFS (adjusted hazard ratio for SUVmax 1.05 [95% confidence interval 1.02–1.08]; log-transformed MTV 1.16 [1.08–1.25]; and log-transformed TLG 1.14 [1.07–1.23]) and OS (SUVmax 1.08 [1.04–1.11]; log-transformed MTV 1.24 [1.12–1.38]; and log-transformed TLG 1.22 [1.11–1.34]) with all P < 0.001. Results based on dichotomized PET parameters were similar to those obtained with continuous values: PFS (adjusted hazard ratio for SUVmax ≥ 7.6, 1.41 [1.08–1.85]; MTV ≥ 21.2 cm 3 , 1.41 [1.08–1.86]; and TLG ≥ 78.9, 1.51 [1.14–1.99]) with P ≤ 0.013 and OS (1.43 [1.01–2.04]; 1.84 [1.28– 2.66]; and 1.73 [1.20–2.50], respectively) with P ≤ 0.046. Conclusion Pretreatment 18F-FDG PET/CT parameters are independent prognostic markers in patients with ER+/HER2- MBC receiving CDK4/6 inhibitors with ET, supporting their potential utility in risk stratification.

Objective: This study aimed to assess the association between exposure to gadolinium-based contrast agents (GBCAs) and the risk of parkinsonism according to the GBCA type. Materials and Methods: Individuals aged ≥40 years who underwent first-ever magnetic resonance imaging (MRI) examinations between 2011 and 2014 were identified from the Korean nationwide population-based health insurance claims database and followed up until 2022. Individuals were divided into those who underwent at least one GBCA-enhanced MRI, and those who underwent only non-enhanced MRI. GBCA-exposed individuals were further categorized into those exposed only to linear or macrocyclic GBCAs, after excluding those exposed to both types. The primary event of interest was allcause parkinsonism. Secondary events included all-cause parkinsonism requiring medication, Parkinson’s disease (PD), atypical parkinsonism, and secondary parkinsonism. Hazard ratios (HRs) were estimated using multivariable Cox proportional hazard regression models for exposure to linear and macrocyclic GBCAs, with the non-enhanced MRI group serving as a reference. The models were adjusted for age, sex, smoking status, alcohol consumption, regular exercise, body mass index, estimated glomerular filtration rate, and comorbidities. Subgroup analyses were performed according to age, sex, renal function, and history of cancer. Results: A total of 222,977 individuals were included in this study. Among them, 92,230, 48,335, and 82,412 individuals underwent non-enhanced, linear GBCA-enhanced, and macrocyclic GBCA-enhanced MRI, respectively. Exposure to linear GBCAs slightly increased the risk of all-cause parkinsonism (adjusted HR, 1.13 [97.5% confidence interval, 1.08–1.19]), while exposure to macrocyclic GBCAs did not increase the risk (adjusted HR, 1.00 [97.5% confidence interval, 0.95–1.05]).The results were similar for all-cause parkinsonism requiring medication, PD, and secondary parkinsonism, whereas no significant association was observed for atypical parkinsonism. Conclusion Exposure to linear GBCAs may slightly increase the risk of parkinsonism in adults, whereas exposure to macrocyclic GBCAs may not. Caution should be exercised when using linear GBCAs until further evidence emerges.

Background: We developed a simplified variant of the ADV score, the AFP-PIVKAII (AP) score for post-transplant hepatocellular carcinoma (HCC) prognosis, which considers only AFP and PIVKA-II levels excluding morphometric tumor size information from the ADV score. This study investigated the prognostic performance of the AP score in predicting HCC recurrence and overall survival (OS) after living donor liver transplantation (LDLT). Methods: We analyzed 843 patients with HCC who underwent LDLT between 2006 and 2015, assessing HCC recurrence and OS in relation to AP score. Results: The median pretransplant AFP and PIVKA-II levels were 12.8 ng/mL and 27 mAU/mL, respectively. The median and mean AP scores were 2.6 log (range: 0.6–9.2 log) and 2.9±1.1 log, respectively. The 5-year time-dependent area under the receiver operating characteristic curve for the AP score in predicting post-transplant HCC recurrence was 0.672 (p<0.001). HCC recurrence and OS curves along AP score intervals of 1.0 log showed statistical differences in accordance with the AP scores (both p<0.001). Using a Youden index J-derived AP score cutoff of 4.0 log, two-tiered groups (ADV <4.0 log vs. ADV ≥4.0 log) showed statistically significant differences in HCC recurrence and OS (both p<0.001). Harrell’s c-indices for AP score with cutoff of 4.0 log and ADV scores with cutoff of 5.0 log regarding HCC recurrence and OS were similar. Conclusion The AP score functions as an integrated surrogate marker for predicting post-transplant outcomes in patients with HCC undergoing LDLT. It may serve as a simplified alternative to the ADV score, particularly in patients with small HCCs.

Necrotizing fasciitis (NF) is a rapidly progressive, life-threatening soft tissue infection that rarely involves the periorbital region. We report an unusual case of periorbital NF caused by methicillin-sensitive Staphylococcus aureus (MSSA) in a previously healthy 48-year-old woman, originating from a neglected, recurrent hordeolum—an otherwise benign eyelid condition. The infection resulted in an extensive fullthickness defect of the upper eyelid and adjacent temporal area, presenting major reconstructive challenges. Reconstruction was performed using a radial forearm free flap combined with a buccal mucosal graft to restore both anterior and posterior lamellae, achieving functional eyelid protection and improved visual acuity. This case highlights the potential for seemingly minor, recurrent eyelid infections to progress rapidly to devastating NF even in the absence of systemic symptoms or risk factors. Early recognition and multidisciplinary management were critical to preventing further morbidity. To our knowledge, MSSA has not previously been reported as a causative agent of periorbital NF, underscoring the need for clinical vigilance and timely intervention in common eyelid conditions to avoid catastrophic complications.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder defined by amyloid-β (Aβ) plaques, tau hyperphosphorylation, and neuroinflammation. Although earlier work emphasized brain-resident glia (microglia and astrocytes), recent studies highlight adaptive immune cells, particularly T and B lymphocytes, as modulators of AD pathology. This review synthesizes animal and human findings from 2022–2025 to provide updated insights into the multifaceted roles and therapeutic potential of adaptive immunity in AD. Infiltration of peripheral T and B cells into the brain parenchyma links peripheral immunity to central nervous system (CNS) pathology. Both infiltrating lymphocytes and resident glia show context-dependent dual effects, either exacerbating neurodegeneration or promoting neuroprotection. Therapeutic strategies under active investigation include modulation of CD4+ T cell differentiation, adoptive transfer of regulatory T cells, and next-generation active vaccines for AD. Overall, selective modulation of discrete immune subsets may enable adaptive-immunity-based treatments, a complex yet promising avenue for AD therapy.

Purpose: Guidelines from the aromatase inhibitor era for early breast cancer (EBC) treatment recommend maintaining a body mass index (BMI) below 25. In the current era of cyclin-dependent kinase (CDK) 4/6 inhibitors, now standard in metastatic breast cancer (MBC), limited data exist on treatment outcomes in obese patients. This study investigates how adiposity affects the treatment outcome of CDK 4/6 inhibitors in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative MBC. Materials and Methods: We searched PubMed, MEDLINE, and Embase databases, assessing efficacy outcomes such as progression-free survival (PFS) based on obesity markers, including BMI and visceral adipose tissue (VAT) index. Results: Twelve studies were reviewed, with seven studies and 1,812 patients included in a pooled meta-analysis. Among patients with BMI ≥ 25, modest improvement in PFS was observed, with a pooled hazard ratio (HR) of 0.944 (95% confidence interval [CI], 0.909 to 0.980; p=0.003). Besides, add-on analysis using VAT to define obesity revealed a notable PFS improvement, with a pooled HR of 0.452 (95% CI, 0.256 to 0.798; p=0.006). Conclusion While BMI-defined obesity showed slight PFS improvement with CDK 4/6 inhibitors and endocrine therapy, using VAT to define obesity revealed significant PFS gains. This highlights the need for further research on biomarker to clarify the role of adiposity in MBC, which may differ from its impact in EBC.

Purpose: Although human epidermal growth factor receptor 2 (HER2) positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy. Materials and Methods: The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed. Results: The analysis included 799 female patients. The median age was 51 years (range, 23 to 79 years), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n=238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% confidence interval [CI], 114.0 to 127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1 to 93.3), 97.5% (95% CI, 96.4 to 98.7), and 98.8% (95% CI, 98.0 to 99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease. Conclusion A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.