Background/Aims: Spinal cord injury (SCI) frequently impairs defecation, severely affecting the quality of life. This study examines compensatory neural remodeling after SCI, focusing on basal colonic contractility, neural responses to electrical field stimulation, and alterations in excitatory cholinergic and inhibitory nitrergic pathways. Methods: Female Sprague–Dawley rats underwent either sham surgery or T10 spinal cord transection and were categorized into 3 groups: sham, 1-week post-SCI (acute), and 4-week post-SCI (chronic). Colonic contractility was assessed in an organ bath using electrical field stimulation in the presence of a nitric oxide synthase inhibitor. Neural protein expression was analyzed by immunofluorescence and Western blotting. Results: SCI produced region- and time-dependent impairments in colonic contractility, with distinct alterations in the proximal circular and longitudinal muscles across acute and chronic phases. Neural excitability shifted dynamically, showing enhanced excitatory activity in the proximal longitudinal muscle at 1-week and the distal circular muscle at 4-week post-SCI. Protein analysis revealed increased neuronal nitric oxide synthase in the proximal colon, decreasedsoluble guanylyl cyclase in the distal colon, upregulated muscarinic M3 receptor in the proximal colon, and reduced vaso-active intestinal peptide receptor 1 in both proximal and distal regions. Conclusion SCI induces spatiotemporal remodeling of excitatory and inhibitory neural pathways, contributing to colonic dysmotility and revealing potential targets for therapeutic intervention.

Purpose: Skeletal muscle, accounting for approximately 40% of the total body mass, plays a critical role in movement, postural support, and metabolic homeostasis. Muscle mass is determined by the balance between protein synthesis and degradation, which is closely regulated by the mitochondrial function. Mitochondrial dysfunctions contribute to muscle loss by promoting oxidative stress and cellular damage. This study examined the effects of masutakeside I, a lignan glycoside derived from Styrax japonicus, on the mitochondrial function and muscle differentiation in C2C12 myoblasts. Methods: C2C12 myoblasts differentiated into myotubes in the presence of masutakeside I (0–10 ng/mL). Myogenic differentiation was assessed by myosin heavy chain (MHC) immunofluorescence, and multinucleated myotubes and relative diameters were quantified.The mitochondrial function was evaluated by measuring the mitochondrial reactive oxygen species (ROS), mitochondrial mass, and mitochondrial membrane potential using MitoSOX, MitoTracker Green, and JC-1 staining, respectively. Gene expression related to muscle differentiation, protein degradation, and the mitochondrial life cycle was analyzed using quantitative reverse transcription polymerase chain reaction. Results: Masutakeside I significantly increased the number of multinucleated (≥ 5 nuclei) MHC-positive myotubes and relative myotube diameter compared to the control. In addition, masutakeside I upregulated the myogenic markers, including phosphoinositide 3-kinase and MHC isoforms (Myh2, Myh4, and Myh7), while significantly downregulating protein degradation–related genes, including mothers against decapentaplegic homolog 2/3, forkhead box protein O1, atrogin-1, and muscle RING finger-1. Masutakeside I modulated the mRNA expression of the mitochondrial function and mitophagy-related markers, suggesting its potential involvement in mitochondrial quality control. Consistent with these effects, the mitochondrial ROS levels decreased, whereas mitochondrial mass and membrane potential increased. Conclusion These findings suggest that masutakeside I modulates the markers related to myogenic differentiation, muscle protein degradation, and mitochondrial function.

Legal risks and liability issues in medical practice serve as a primary catalyst for the current collapse of essential healthcare services in Korea. Currently, medical disputes in Korea are disproportionately focused on criminal prosecutions and high-damages civil litigation. This punitive approach fosters a culture of concealment, encourages defensive medicine, and accelerates the exodus of medical professionals from essential fields. Ultimately, this cycle deprives the system of opportunities for improvement and poses a significant threat to patient safety. In contrast, many advanced nations have adopted principles of “Just Culture” and “Safe Space,” prioritizing non-punitive reporting and systemic root-cause analysis over individual retribution. To address these issues, this paper proposes four key strategies: First, the establishment of an independent “Patient Safety Investigation Agency” to objectively investigate incidents and identify systemic flaws. Second, a transition from criminal punishment to licensing board-led management, focusing on re-education and counseling to maintain quality of care. Third, the enactment of “Apology Laws” to ensure that expressions of regret or apologies cannot be used as legal evidence of liability, thereby fostering trust and psychological recovery. Finally, the creation of a “Patient Safety Fund” to provide prompt and sufficient public compensation to victims regardless of proven negligence. In conclusion, it is imperative to shift the paradigm by defining medical accidents as “system failures” rather than individual faults. Strengthening the social safety net will encourage medical professionals to return to essential care and build a sustainable healthcare environment centered on patient safety.

South Korea’s current healthcare system stands at a critical crossroads that will determine whether it can progress in a better direction over the next decade. Behind the relatively stable level of population health that has been maintained until now, it has become clear that the deterioration of patient experiences, the risk of collapse in critical emergency medical services, the burnout of healthcare providers, and the crisis in the sustainability of healthcare finances have all accumulated simultaneously. This crisis can no longer be overcome by partial fixes or short-term measures alone. The answer to what needs to change first must begin with a reaffirmation of what the healthcare system should aim for. Ultimately, what needs to be changed now is not an individual policy, but the criteria and priorities through which we view healthcare. The focus must shift from what to provide more of, to questioning what holds greater social value. If such a shift does not begin now, in ten years we won’t face a better healthcare system, but care enmeshed in a deeper crisis. Now is precisely the time to fundamentally define the direction of the healthcare system.

Background: A systematic evaluation of potential living liver donors is essential to ensure donor safety and optimize recipient outcomes in living donor liver transplantation (LDLT). This study aimed to assess donor acceptance rates and reasons for disqualification among individuals evaluated for LDLT at a high-volume transplant center over a one-year period. Methods: We retrospectively reviewed 1,087 potential living liver donors who presented for LDLT evaluation in 2023. Of these, 991 candidates advanced beyond the initial screening (Stage 1) and underwent comprehensive clinical, imaging, and pathological assessments (Stages 2 and 3). Candidates who discontinued after Stage 1 were excluded due to the absence of documented reasons for non-progression. Results: Among the 991 candidates who proceeded beyond initial screening, 473 (47.7%) completed the full donor evaluation, of whom 466 were judged to be suitable donors. Among suitable donors, 384 (82.4%) proceeded to donor hepatectomy, whereas 82 did not, primarily due to recipient-related factors such as clinical deterioration or withdrawal of consent. Donor ineligibility was determined in 422 candidates (42.6%), most commonly due to inadequate remnant liver volume (52.8%), hepatic steatosis (20.6%), and insufficient graft size (10.2%). Among candidates undergoing Stage 2 evaluation, 162 (16.3%) failed to meet steatosis criteria; 126 were excluded solely for steatosis and advised weight reduction, and 39 subsequently became eligible and successfully donated. Conclusion In this high-volume LDLT center, donor disqualification was primarily driven by remnant liver volume and hepatic steatosis. Targeted interventions such as weight reduction enabled successful donation in a subset of initially ineligible candidates, underscoring the importance of individualized donor evaluation and pre-donation optimization.

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.

Background: Inferior orbital blowout fractures (BOF) cause ocular symptoms like diplopia and extraocular muscle limitation, influenced by inferior rectus muscle (IRM) status. This study evaluated the relationship between preoperative IRM status on computed tomography (CT) and ocular symptom recovery time. Methods: This retrospective study analyzed 127 patients with inferior BOF and ocular symptoms (2012–2024). Inclusion criteria included age 18–80 years and preoperative CT availability. IRM status was assessed for bone interruption, herniation extent, and swelling (short/ long axis ratio < 0.54 or ≥ 0.54). Recovery times were analyzed using t-tests and Kaplan-Meier survival analysis (p< 0.05). Results: Of 127 patients (mean age, 35 years; 67.7% male), 66 (52.0%) recovered from ocular symptoms within 7 days, 53 (41.7%) within 30–90 days, and eight (6.3%) had diplopia that remained as a permanent sequela at the last follow-up. Diplopia recovery time was longer in IRM–bone contact (16.9± 5.5 days, n= 35) and bone-pierced IRM (29.4± 10.3 days, n= 15) groups versus no-contact (5.1± 4.2 days, n= 77; p= 0.02, t-test). Herniation and swelling showed no significant correlation (p> 0.05). Conclusion Preoperative CT-based assessment of the IRM–bone interface predicts diplopia recovery time, with bone-pierced IRM linked to prolonged recovery. Patients with bone-pierced IRM may require closer follow-up and careful consideration of timely surgical management.

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.

Background: and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition. Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD. Methods: This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores. Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES. Mutant-allele risk scores (MARSs) were created based on WESidentified mutations. Gene-based association analyses and pooled analyses in East-Asian populations were further performed. Results: Fourteen mutations reached the genome-wide significance criterion (p<5×10-8 ), among which the p.R4810K mutation in the ring finger protein 213 gene (RNF213) showed the strongest significance (odds ratio=117.4, p=8.54×10-24 ). Notably, two mutations—p.G576S (alpha-glucosidase [GAA]) and p.D54N (charged multivesicular body protein 6 [CHMP6])— exhibited high CADD scores of 32 and 25, respectively, whereas the RNF213 p.R4810K mutation demonstrated a moderate deleteriousness score of 10.63. Fourteen mutations exhibited significant differences in allele frequencies between patients and UKB controlled data (p<1×10-8 ).The MARS9 model (incorporating nine missense mutations) showed better predictability for MMD (90.89%). The analysis of gene-based associations revealed four candidate genes: GAA, RNF213, CHMP6, and CARD14 (p=5×10-19 to 4×10-7 ). The subsequent pooled analyses validated four mutations in East Asian populations: p.V1195M, p.D1331G, p.S2334N, and p.R4810K (p<3×10-8 ). Conclusions This pioneering study has corroborated the significance of p.R4810K and identified several causative mutations predisposing patients to MMD, which helps to improve the understanding of its polygenetic nature.

Background: and Purpose Intraoperative visual evoked potential (VEP) monitoring has been studied mainly in pituitary adenoma, while its role in nonpituitary suprasellar tumors has remained unclear. This study evaluated the predictive usefulness of intraoperative VEP monitoring during endoscopic endonasal surgery (EES) and aimed to identify optimal alarm criteria for visual outcomes. Methods: We retrospectively analyzed a cohort of 87 patients who underwent EES with intraoperative VEP monitoring between April 2021 and September 2023. Visual outcomes were evaluated preoperatively and at short-term (≤3 months) and long-term (12 months) followups, with visual deterioration at these time points defined as worsening of either visual acuity or the visual field. Reductions in the VEP amplitude were quantified using both the maximum intraoperative decrease and the final amplitude after recovery. Receiver operating characteristic (ROC) curve analyses were performed to identify the optimal alarm thresholds, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated for short-term and long-term visual deteriorations. Results: Short-term and long-term visual deteriorations were detected in 12 (9.2%) and 5 (3.8%) of the 130 analyzed eyes, respectively. ROC curve analyses identified ≥40% and ≥30% reductions in the N75–P100 amplitude as optimal alarm criteria for short-term and long-term visual deteriorations, respectively. A 30% reduction without intraoperative recovery demonstrated markedly higher sensitivity than the conventional 50% alarm threshold for short-term (58.3% vs. 33.3%) and long-term (80.0% vs. 20.0%) outcomes, while maintaining acceptable specificity (82.2% and 80.8%, respectively). Conclusions A 30% reduction in amplitude represents a more-sensitive and clinically relevant alarm threshold than a 50% reduction for intraoperative VEP monitoring during EES for nonpituitary suprasellar tumors. Incorporating both the magnitude and recovery pattern of VEP amplitude changes may improve the accuracy of predictions of long-term visual deterioration. However, the potential for false positives warrants cautious interpretation, and further studies are needed to validate the impact of intraoperative VEP monitoring on visual outcomes.