Charcot neuroarthropathy (CN), also known as Charcot arthropathy, is a complex, progressive disorder primarily affecting the foot and ankle. This case report describes a multifaceted management strategy for a 54-year-old male with diabetes mellitus, end-stage renal disease, and presumed underlying Charcot arthropathy who experienced a traumatic ankle fracture. The initial surgical plans were delayed because of systemic infection indicators, including elevated C-reactive protein levels and high fever. The patient underwent multiple surgical interventions and faced challenges, including metal failure, implant-associated infection, and tibiotalar joint dislocation. A multidisciplinary approach involving orthopedic surgeons, nephrologists, and endocrinologists was crucial for managing the case effectively.In particular, the patient declined a below-knee amputation and opted for comprehensive surgical intervention, resulting in improved functionality at the latest follow-up. This case highlights the complexities of managing CN in patients with multiple comorbidities and emphasizes the need for a nuanced, patient-centered approach.

Background: To identify the optimal surgical technique for single-level anterior cervical discectomy and fusion (ACDF), this study compared surgical outcomes and incidence of adjacent segment degeneration (ASD) in patients undergoing single-level ACDF using cage alone single-level fusion and plate fixation techniques. Methods: This single-center retrospective study (2003–2018) included patients who underwent single-level ACDF with either plate fixation (PLATE) or cage (CAGE) alone. The radiologic and clinical outcomes between the 2 surgical groups were compared over a 4-year follow-up period. Outcomes of interest included parameters related to range of motion, sagittal alignment, as well as fusion, subsidence, and ASD rates. Clinical outcomes were evaluated using the Neck Disability Index (NDI) and visual analog scale (VAS) for pain. Dysphagia and hoarseness rates were estimated based on medical records. Results: Forty-seven patients were included (n=17 in CAGE group). In the CAGE group, 94.1% of the patients had Bridwell grade 1 or 2, compared to 83.3% in the PLATE group (p = 0.396). Subsidence occurred in 12.5% and 3.6% of the CAGE and PLATE cases, respectively (p = 0.543). Segmental kyphosis progressed in the CAGE group compared to the PLATE group at 12, 24, and 48 months (p < 0.001). Radiographic ASD was observed in 41.2% and 30.0% of patients in the CAGE and PLATE groups, respectively, with a higher incidence in the upper segments for both groups. Preoperative NDI scores were similar between the groups; however, postoperatively, the CAGE group had significantly lower NDI scores (3.50 ± 2.74 vs. 8.00 ± 5.81) at 4 years (p = 0.020). Neck pain VAS scores also showed significant improvement in the CAGE group (2.33 ± 2.94) compared with that in the PLATE group (3.07 ± 2.31) at 4 years (p = 0.045). Both groups showed comparable arm pain VAS scores at 2 and 4 years postoperatively. Postoperative dysphagia occurred in 1 patient in the PLATE group, resolving almost completely by 1 year. Conclusions Single-level ACDF using a cage alone technique demonstrated favorable radiologic and clinical outcomes overall compared to plate-augmented ACDF. However, plate augmentation is recommended for patients with severe cervical kyphosis or those at high risk of subsidence.

Background: and Purpose: Amyloid-beta (Aβ) plaques are key in Alzheimer’s disease (AD), with Aβ positron emission tomography imaging enabling non-invasive quantification.To address regional Aβ deposition, we developed regional Centiloid scales (rdcCL) and commercialized them through the computed tomography (CT)-based BeauBrain Amylo platform, eliminating the need for three-dimensional T1 magnetic resonance imaging (MRI). Objective: We aimed to establish robust regional Aβ cutoffs using the commercialized BeauBrain Amylo platform and to explore the prevalence of subgroups defined by global, regional, and striatal Aβ cutoffs across cognitive stages. Methods: We included 2,428 individuals recruited from the Korea-Registries to Overcome Dementia and Accelerate Dementia Research project. We calculated regional Aβ cutoffs using Gaussian Mixture Modeling. Participants were classified into subgroups based on global, regional, and striatal Aβ positivity across cognitive stages (cognitively unimpaired [CU], mild cognitive impairment, and dementia of the Alzheimer’s type). Results: MRI-based and CT-based global Aβ cutoffs were highly comparable and consistent with previously reported Centiloid values. Regional cutoffs revealed both similarities and differences between MRI- and CT-based methods, reflecting modality-specific segmentation processes. Subgroups such as global(−)regional(+) were more frequent in non-dementia stages, while global(+)striatal(−) was primarily observed in CU individuals. Conclusions Our study established robust regional Aβ cutoffs using a CT-based rdcCL method and demonstrated its clinical utility in classifying amyloid subgroups across cognitive stages. These findings highlight the importance of regional Aβ quantification in understanding amyloid pathology and its implications for biomarker-guided diagnosis and treatment in AD.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Background/Aims: The incidence of steatotic liver disease (SLD) is increasing across all age groups as the incidence of obesity increases worldwide. The existing noninvasive prediction models for SLD require laboratory tests or imaging and perform poorly in the early diagnosis of infrequently screened populations such as young adults and individuals with healthcare disparities. We developed a machine learning-based point-of-care prediction model for SLD that is readily available to the broader population with the aim of facilitating early detection and timely intervention and ultimately reducing the burden of SLD. Methods: We retrospectively analyzed the clinical data of 28,506 adults who had routine health check-ups in South Korea from January to December 2022. A total of 229,162 individuals were included in the external validation study. Data were analyzed and predictions were made using a logistic regression model with machine learning algorithms. Results: A total of 20,094 individuals were categorized into SLD and non-SLD groups on the basis of the presence of fatty liver disease. We developed three prediction models: SLD model 1, which included age and body mass index (BMI); SLD model 2, which included BMI and body fat per muscle mass; and SLD model 3, which included BMI and visceral fat per muscle mass. In the derivation cohort, the area under the receiver operating characteristic curve (AUROC) was 0.817 for model 1, 0.821 for model 2, and 0.820 for model 3. In the internal validation cohort, 86.9% of individuals were correctly classified by the SLD models. The external validation study revealed an AUROC above 0.84 for all the models. Conclusions As our three novel SLD prediction models are cost-effective, noninvasive, and accessible, they could serve as validated clinical tools for mass screening of SLD.

γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators. Reactive oxygen species (ROS) levels, antioxidant enzyme expression, NRF2 expression, and nuclear translocation were higher in SNUC5/RR cells irradiated with or without 8 Gy than in SNUC5 cells. The DNA demethylase ten-eleven translocation 1 (TET1) expression and TET1 binding to the NRF2 promoter in SNUC5/RR cells were stronger than those in SNUC5 cells, indicating lower methylation of CpG islands in the NRF2 promoter.TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.