Background: Acute deterioration of patients in general wards often leads to major adverse events (MAEs), including unplanned intensive care unit transfers, cardiac arrest, or death. Traditional early warning scores (EWSs) have shown limited predictive accuracy, with frequent false positives. We conducted a prospective observational external validation study of an artificial intelligence (AI)-based EWS, the VitalCare - Major Adverse Event Score (VC-MAES), at a tertiary medical center in the Republic of Korea. Methods: Adult patients from general wards, including internal medicine (IM) and obstetrics and gynecology (OBGYN)—the latter were rarely investigated in prior AI-based EWS studies—were included. The VC-MAES predictions were compared with National Early Warning Score (NEWS) and Modified Early Warning Score (MEWS) predictions using the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and logistic regression for baseline EWS values. False-positives per true positive (FPpTP) were assessed based on the power threshold. Results: Of 6,039 encounters, 217 (3.6%) had MAEs (IM: 9.5%, OBGYN: 0.26%). Six hours prior to MAEs, the VC-MAES achieved an AUROC of 0.918 and an AUPRC of 0.352, including the OBGYN subgroup (AUROC, 0.964; AUPRC, 0.388), outperforming the NEWS (0.797 and 0.124) and MEWS (0.722 and 0.079). The FPpTP was reduced by up to 71%. Baseline VC-MAES was strongly associated with MAEs (P<0.001). Conclusions The VC-MAES significantly outperformed traditional EWSs in predicting adverse events in general ward patients. The robust performance and lower FPpTP suggest that broader adoption of the VC-MAES may improve clinical efficiency and resource allocation in general wards.

Background: Despite advances in systemic targeted therapies, topical agents remain the primary treatment for localized psoriasis. However, their therapeutic effects are often delayed and unsatisfactory. The dissolving microneedle (DMN) patch, a novel transdermal drug delivery system, enhances the absorption of topical agents through micro-channels. Objective: To evaluate the efficacy of DMN patches in enhancing drug delivery and improving clinical outcomes in psoriatic plaques. Methods: A prospective, randomized, split-body study was conducted to verify the efficacy of additional use of DMN patches after topical agent application in psoriasis treatment. Patients with mild psoriasis were enrolled and 6 paired lesions per patient were randomized into 3 groups: ointment-only, ointment-with-no needle patch, and ointment-with-DMN patch. Lesions were treated with a topical agent (betamethasone and calcipotriol) once daily for 2 weeks. Modified psoriasis area and severity index (mPASI) scores were measured weekly. In vitro and ex vivo experiments were performed to confirm micro-channel formation, microneedle dissolution, and drug penetration enhancement. Results: A total of 132 paired lesions from 22 patients were analyzed. The ointment-with-DMN patch group showed significantly improved mPASI scores (80.4%±20.5%; 5.42→1.06) compared to the ointment-with-no needle patch (64.6%±33.0%; 4.94→1.68) (p<0.05) and ointment-only groups (55.5%±31.4%; 5.00→2.15) (p<0.001). In vitro studies demonstrated 2.1-fold enhanced drug delivery with DMN patches, while ex vivo histological analysis confirmed micro-channel formation. No adverse events, including infection or psoriasis exacerbation, were observed. Conclusion The DMN patch is an effective adjunctive tool that enhances transdermal drug delivery and improves therapeutic outcomes in psoriatic plaques, particularly those refractory to topical agents.

Vancomycin, a vital antibiotic for treating gram-positive bacterial infections, requires therapeutic drug monitoring (TDM) because of its substantial pharmacokinetic variability. While traditional TDM relies on steady-state trough concentrations, recent guidelines advocate the area under the concentration–time curve (AUC) as the target index. However, detailed protocols for AUC estimation are lacking, leading to potential discrepancies among institutions. We surveyed medical institutions in Korea regarding vancomycin TDM, including AUC estimation. Nineteen participants responded to the TDM case challenge under three patient scenarios. For an ordinary patient in Case 1, the overall CV for AUC values was 0.4% when both trough and peak concentrations were included in the AUC calculation and 1.9% when utilizing only the trough concentration. For Case 2, an older patient with obesity, the corresponding CV was 6.6%. For Case 3 with multiple trough concentrations, the CV was 15.6%, reflecting variations in the selective use of data. Although the agreements in Case 1 were good, significant variability in AUC estimation was noted in cases involving atypical patient characteristics or old TDM data. Our study provides insight into the current status of vancomycin TDM in Korea and underscores the need for standardized operational protocols for AUC estimation.

Background: TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications. Methods: This study included patients aged ≥ 18 yrs who were diagnosed as having MDS(N = 1,244) or AML (N = 2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed. Results: TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/ R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF > 50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Conclusions Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

Purpose: Patients undergoing breast surgery may experience chronic postoperative pain in the breasts, upper extremities, and axillary regions, and no established methods for preventing this pain are available at present. This study aimed to investigate whether coaptation of the transected intercostal nerve can prevent the development of neuropathic and chronic breast pain after mastectomy in implant-based breast reconstruction. Methods: A prospective, double-blind, randomized controlled trial was conducted by dividing patients who underwent implant-based breast reconstruction after mastectomy into a control group without nerve coaptation and an experimental group with nerve coaptation.Patient clinical information was collected, and a survey using the pain and quality of life scale was conducted at 6 and 12 months after surgery. Results: Fifteen patients completed the study, including seven in the control group and eight in the experimental group. The two groups showed no significant differences in terms of clinical factors. The experimental group exhibited lower Short-Form McGill Pain Questionnaire scores than the control group at 6 and 12 months postoperatively, with a statistically significant difference at 6 months. Numerical Rating Scale and Present Pain Intensity scores for both groups were in the “no to mild” range throughout the study period, with no statistically significant differences between the groups. Although the difference in the BREAST-Q™ results did not reach statistical significance, the experimental group showed an improvement in the quality of life. Conclusion Intercostal nerve coaptation after mastectomy in implant-based breast reconstruction may facilitate initial nerve recovery. Although trial results are needed to fully determine the clinical impact, our findings support the ongoing scientific and clinical efforts to use this technique.

Background: and Purpose The risk factors for developing epilepsy following febrile convulsion (FC) have been studied extensively, but the underlying genetic components remain largely unexplored. Our objective here was to identify the risk loci related to FC through a genomewide association study of Korean epilepsy patients. Methods: We examined associations between a history of FC and single-nucleotide polymorphisms (SNPs) in data obtained from 125 patients with focal epilepsy: 28 with an FC history and 97 without an FC history. Results: Among 288,394 SNPs, 5 candidate SNPs showed p<1×10-4 . Regional association plots of these SNPs identified a novel locus adjacent to PROX1 that is implicated in hippocampal neurogenesis and epileptogenesis. The allele frequencies of the SNPs upstream of PROX1 including two candidate SNPs (rs1159179 and rs7554295 on chromosome 1) differed significantly between the groups with and without an FC history. In contrast, the allele frequencies of the SNPs inside PROX1 showed no differences, indicating dysregulated expression of PROX1 rather than a functional alteration in the PROX1 protein. Conclusions This novel discovery of SNPs upstream of PROX1 suggests that the dysregulated expression of PROX1 contributes to the development of focal epilepsy following FC. We propose that these SNPs are potential genetic markers for focal epilepsy following FC, and that PROX1 represents a potential therapeutic target of antiseizure medications.

Background: and Purpose The National Brain Biobank of Korea (NBBK) is a brain bank consortium supported by the Korea Disease Control and Prevention Agency and the Korea National Institute of Health, and was launched in 2015 to support research into neurodegenerative disease dementia (NDD). This study aimed to introduce the NBBK and describes clinicopathological correlations based on analyses of data collected from the NBBK. Methods: Four hospital-based brain banks have been established in South Korea: Samsung Medical Center Brain Bank (SMCBB), Seoul National University Hospital Brain Bank (SNUHBB), Pusan National University Hospital Brain Bank (PNUHBB), and Myongji Hospital Brain Bank (MJHBB). Clinical and pathological data were collected from these brain banks using standardized protocols. The prevalence rates of clinical and pathological diagnoses were analyzed in order to characterize the clinicopathological correlations. Results: Between August 2016 and December 2023, 185 brain specimens were collected and pathologically evaluated (SNUHBB: 117; PNUHBB: 27; SMCBB: 34; MJHBB: 7). The age at consent was 70.8±12.6 years, and the age at autopsy was 71.7±12.4 years. The four-most-common clinical diagnoses were Alzheimer’s disease (AD) dementia (20.0%), idiopathic Parkinson’s disease (15.1%), unspecified dementia (11.9%), and cognitively unimpaired (CU) (11.4%).Most cases of unspecified dementia had a pathological diagnosis of central nervous system (CNS) vasculopathy (31.8%) or AD (31.8%). Remarkably, only 14.2% of CU cases had normal pathological findings. The three-most-common pathological diagnoses were AD (26.5%), CNS vasculopathy (14.1%), and Lewy body disease (13.5%). Conclusions These clinical and neuropathological findings provide a deeper understanding of the mechanisms underlying NDD in South Korea.