Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery. Methods: In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63). Results: The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy. Conclusions Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.

Background/Aims: Peptic ulcer bleeding (PUB) is a major cause of nonvariceal gastrointestinal bleeding. As the older population increases, the prevalence of sarcopenia is also growing. Although sarcopenia influences the prognosis of various diseases, its association with clinical outcomes of PUB remains unknown. Therefore, this study aimed to explore this correlation. Methods: We retrospectively analyzed 2,050 patients who underwent esophagogastroduodenoscopy for suspected gastrointestinal bleeding between January 2014 and December 2021. Patients who underwent computed tomography scans were included for sarcopenia evaluation based on the psoas muscle index, defined as the total psoas area normalized by the square of the height of the patient. Sarcopenia was defined using specific cutoffs: ≤7.3 cm2/m2 and ≤5.1 cm2/m2 for men and women, respectively. The primary outcome measured was the 30-day mortality rate. Results: Out of 358 patients, 149 were diagnosed with sarcopenia. The 30-day mortality rate was significantly higher in patients with sarcopenia than in those without. Multivariate regression analysis revealed significant associations between sarcopenia, a high age, blood tests, and comorbidity score, and administration of inotropic agents with 30-day mortality. Conclusions Our study showed that the presence of sarcopenia, elevated comorbidity scores, and use of inotropes were associated with higher 30-day mortality rates. Considering that sarcopenia may influence the clinical outcomes in patients with PUB, it is crucial to manage patients with sarcopenia with particular care.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

Objective: We aimed to investigate the effectiveness of buspirone as an adjunctive therapy for alleviating anxiety symptoms in patients with depressive disorders who are already taking antidepressants. Methods: This was an open-label prospective multicenter non-interventional observational study conducted over 12 weeks. We enrolled 180 patients diagnosed with depressive disorders according to DSM-5 criteria and Hamilton Anxiety Rating Scale (HAMA) scores ≥ 18. Participants were already taking selective serotonin reuptake inhibitors or serotoninnorepinephrine reuptake inhibitors and were prescribed adjunctive buspirone. Efficacy was assessed using HAMA, Hamilton Depression Rating Scale (HAMD), Clinical Global Impression Scale-Improvement, Clinical Global Impression Scale-Severity, Sheehan Disability Scale (SDS), and WHO-5 Well-Being Index. Results: The efficacy analysis included 161 patients. HAMA scores decreased significantly from 25.2 ± 6.7 at baseline to 15.4 ± 8.6 at 12 weeks (p ＜ 0.001), whereas HAMD scores decreased from 19.4 ± 4.6 to 12.7 ± 5.7 (p ＜ 0.001).WHO-5 and SDS scores showed significant improvements. The HAMA response rate was 39.1% and the remission rate was 13.7% at 12 weeks. Adverse drug reactions were reported in 3.7% of participants. Subgroup analyses showed no significant differences in treatment response based on buspirone dosage, baseline anxiety/depression severity, or benzodiazepine use. Conclusion Adjunctive buspirone therapy effectively improved anxiety symptoms in depressed patients taking antidepressants, regardless of baseline symptom severity or buspirone dosage. The treatment was well-tolerated with few adverse events. Future studies using a control group are needed.

Objective: Recently, various mental health promotion programs using virtual reality (VR) technology have been tried in the psychiatric field. Considering the importance of mental health in pregnant women, VR-assisted mental health promotion programs for pregnant women are needed to be developed. This study aimed to prospectively investigate the efficacy of a VR-assisted mental health promotion program for pregnant women. Methods: Fifty-five pregnant women were participated in this study. Mental health states such as depression, anxiety, perceived stress, and quality of life were assessed by Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Perceived Stress Scale, and World Health Organization Quality of Life Scale Abbreviated Version (WHOQOL-BREF) before and after using VR program treatment. Based on the mental health types of pregnant women classified by cluster analysis, the effects of the VR program were analyzed by paired t test and Wilcoxon signed rank test. Results: The VR program significantly reduced PHQ-9 (p = 0.033) and GAD-7 (p = 0.046) scores, and significantly increased WHOQOL-BREF (p = 0.026) score of the participants. Additionally, when classifying the mental health types of pregnant women, the VR program was significantly effective to improve depression, anxiety, and quality of life in the most severe group based on the cluster analysis. Conclusion The results of this study suggest that VR program may be effective to improve the mental health of pregnant women. Particularly, VR programs for the high-risk group of depression might be the most effective. Therefore, VR-assisted mental health promotion programs could be useful for managing the mental health in pregnant women.

The detrimental effects of hyperlipidemia on the healing of rotator cuff tears are well documented. The proposed underlying mechanisms for these effects include alterations in the extracellular matrix, inflammation, and oxidative stress, which hamper the reparative processes in the affected tendon tissues. Recent therapeutic strategies target these pathways, reflecting a growing body of research dedicated to mitigating these effects and promoting healing. This literature review aims to provide a comprehensive understanding of the pathophysiology underlying rotator cuff tears, examine the interplay between hyperlipidemia and rotator cuff tear healing, synthesize current knowledge on contributing biological mechanisms, and outline potential therapeutic interventions to optimize clinical management and treatment outcomes for patients.

Background: Not reducing the posterior malleolar fragment could have an impact on the alignment and stability of syndesmosis since the posterior inferior tibiofibular ligament (PITFL) originates at the posterior malleolar fragment. Given that these alignment and stability changes may contribute to discomfort and pain, further research may be required. We think that our new classification method will be able to help improve understanding of treatment methods for posterior malleolar fractures. Methods: We retrospectively analyzed 206 patients who underwent surgeries for ankle fractures in our orthopedic clinic between April 2014 and December 2022 and were verified to have posterior malleolar fractures in plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI). We performed a probing test to determine whether syndesmosis was stable. Results: We were able to classify the 206 cases into the following 5 types: type 1 (31 cases, 15.0%), extraincisural fragment with an intact fibular notch; type 2 (98 cases, 47.5%), posterolateral fragment extending into the fibular notch; type 3 (37 cases, 17.9%), posteromedial 2-part fragment involving the medial malleolus; type 4 (19 cases, 9.2%), large posterolateral triangular fragment;and type 5 (21 cases, 10.1%), shell-like PITFL avulsion (< 2 mm) in a CT axial view or PITFL periosteal sleeve avulsion (PITPSA) in arthroscopic or MRI findings. Conclusions This new system that adds the PITPSA type for the classification of posterior malleolar fractures may be a useful approach to managing these injuries and may aid in treatment decision-making. It could be important to consider ligament surgery when treating PITPSA.

Background: This study aimed to compare the effectiveness and complications between classic palmaris longus tendon landmark-based corticosteroid injection (CI) and transverse carpal ligament (TCL)-penetrating CI for carpal tunnel syndrome (CTS). Methods: We performed a landmark-based CI on one hand and a TCL-penetrating CI on the other side after randomization in 30 consecutive patients with bilateral CTS. The pain visual analog scale (VAS) and the Boston Carpal Tunnel Questionnaire (BCTQ) were assessed at baseline, 4 weeks, and 3 and 6 months after injection. Skin hypopigmentation of the injection site was evaluated using the modified Vancouver scar scale (mVSS). Pain during needle insertion was evaluated using a VAS for each hand. Results: The mean patient age was 56 ± 11 years (range, 32–77 years), and 27 patients (90.0%) were women. The pain VAS, BCTQ scores, and the incidence of skin hypopigmentation were not significantly different between the 2 groups after injection, but the mean mVSS scores were significantly higher in the landmark-based CI group at all time points. The pain VAS score during needle insertion was significantly higher in the TCL-penetrating CI group. Conclusions When comparing the pain VAS and BCTQ scores, the difference between the 2 groups was not statistically significant. TCL-penetrating CI causes considerable pain during needle insertion but causes less severe skin hypopigmentation than landmark-based CI in CTS treatment.