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: Direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus. This study investigated whether metabolic dysfunction influences the likelihood of fibrosis regression after DAA treatment in patients with chronic hepatitis C (CHC). Methods: This multicenter, retrospective study included 8,819 patients diagnosed with CHC who were treated with DAAs and achieved a sustained virological response (SVR) between January 2014 and December 2022. Fibrosis regression was defined as a 20% reduction in noninvasive surrogates for liver fibrosis, such as liver stiffness (LS) measured by vibration-controlled transient elastography (VCTE) and the fibrosis-4 (FIB-4) score. Hypercholesterolemia (h-TC) was defined as >200 mg/dL. Results: The median age of the study population was 59.6 years, with a predominance of male patients (n=4,713, 57.3%). Genotypes 1, 2, and others were confirmed in 3,872 (46.2%), 3,487 (41.6%), and 1,024 (12.2%) patients, respectively. Diabetes mellitus (DM) was present in 1,442 (17.2%) patients and the median LS was 7.50 kPa (interquartile range, 5.30–12.50). Multivariate analysis revealed that the presence of DM and pre-DAA h-TC were independently associated with a decreased probability of fibrosis regression by VCTE. Additionally, pre-DAA h-TC was independently associated with a decreased probability of fibrosis regression by the FIB-4. Conclusions Metabolic dysfunction has an unfavorable influence on fibrosis regression in patients with CHC who achieve SVR after DAA treatment.

Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. Multiphasic computed tomography or MRI is the standard for HCC diagnosis, but histological confirmation should be considered, especially when inconclusive findings are seen on cross-sectional imaging. Staging and treatment decisions are complex and should be made in multidisciplinary settings, incorporating multiple factors including tumor burden, degree of liver dysfunction, patient performance status, available expertise, and patient preferences. Early-stage HCC is best treated with curative options such as resection, ablation, or transplantation. For intermediate-stage disease, locoregional therapies are primarily recommended although systemic therapies may be preferred for patients with large intrahepatic tumor burden. In advanced-stage disease, immune checkpoint inhibitor-based therapy is the preferred treatment regimen. In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.

Background/Aims: This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV). Methods: Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified. Results: Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05). Conclusions This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.

Background: This study aimed to assess the severity of postoperative delirium (PD) in elderly patients who underwent reverse total shoulder arthroplasty (rTSA) for irreparable massive rotator cuff tears (mRCTs) under general anesthesia (GA) compared to those under interscalene block (IB). Methods: Forty elderly patients aged 65 years or older diagnosed with an irreparable mRCT who underwent rTSA were included in the prospective case-controlled study. Of these, 20 patients were operated under GA and the other 20 under IB. The average age was 77.1 years (range, 65–95 years). The severity of delirious symptoms was evaluated by the Delirium Rating Scale–revised–98 (DRS) score from the patients or guardians before the surgery and at 0, 3, and 7 days and 1, 3, and 6 months after the surgery and compared between the 2 groups. Results: Immediately after surgery, the visual analog scale score difference between the groups was statistically significant, with the GA group at 6.25 (standard deviation, ± 0.85) and the IB group at 3.80 (± 0.62) (p < 0.001). On the day of operation, the mean DRS score in the GA and IB groups were 9.10 (± 5.63) and 6.60 (± 5.33), respectively (p = 0.157). On day 3 of surgery, the mean DRS score in the GA group peaked to 9.95 (± 8.73), while in the IB group, it declined to 6.40 (±5.81) (p = 0.138). After 3 days, DRS scores showed a decreasing trend in both groups. When comparing the mean change (∆) from the preoperative baseline scores to the postoperative values, the ∆DRS score was significantly higher with 4.15 (± 4.53) points in the GA group as compared to 1.30 (± 1.92) in the IB group (p = 0.014). Conclusions IB can be an attractive and efficient anesthetic choice in preventing PD for elderly patients undergoing rTSA for irreparable mRCTs. The IB group showed lower DRS scores and a peak on day 0 compared to the higher DRS scores and peak on day 3 in the GA group. Additionally, IB showed less pain than GA.

Background: Studies comparing the minimally invasive proximal chevron and Akin osteotomies (MIPCA) technique with conventional techniques, such as the open proximal chevron metatarsal osteotomy with the Akin procedure (open PCMO-Akin procedure), are limited. This study aimed to compare and evaluate operative MIPCA and open PCMO-Akin procedure outcomes in the surgical correction of moderate-to-severe hallux valgus deformities. Methods: We conducted a retrospective comparison of clinical and radiographic outcomes between the MIPCA and open PCMOAkin procedure in patients with a hallux valgus deformity, defined as a preoperative hallux valgus angle (HVA) of ≥ 30° and/or a first to second intermetatarsal angle of ≥ 13°. The postoperative complication rate was monitored in both groups for a minimum of 12 months. An unsatisfactory correction was defined as an HVA > 15° at final follow-up. Results: We assigned 58 and 99 patients to the MIPCA or open PCMO-Akin procedure group, respectively. At final follow-up, no significant differences were observed between the groups in terms of clinical and radiographic parameters (p > 0.05), with the exception of the distal metatarsal articular angle (DMAA) (p = 0.012). No statistically significant postoperative changes in the DMAA were observed in the MIPCA group (p = 0.875). Five patients (5.1%) experienced postoperative hallux varus in the open PCMO-Akin procedure group, whereas no such cases were observed in the MIPCA group. No statistically significant difference in the rate of unsatisfactory correction was observed between the groups at the final follow-up (MIPCA group, 15.5%; open PCMO-Akin procedure group, 10.1%; p = 0.315). Conclusions The MIPCA technique is a viable alternative to the open PCMO-Akin procedure for correcting moderate-to-severe hallux valgus deformities. Given the potential lack of postoperative changes in the DMAA following the MIPCA technique, careful consideration is advised when applying this technique to patients with a large DMAA.

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.

Four soluble factors—putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102—were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45–55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.

Background/Aims: Inflammatory bowel disease (IBD) affects health-related quality of life (HRQoL). The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score is strongly correlated with HRQoL in IBD patients. This study aimed to assess the factors influencing HRQoL in IBD patients. Methods: In this prospective study, all patients with ulcerative colitis (UC) and Crohn’s disease (CD) completed the SIBDQ at enrollment; some patients also completed a second SIBDQ at follow-up. Multiple linear regression analysis was used to determine associations between SIBDQ scores and clinical factors. Results: A total of 1,020 patients participated (UC, 67%; CD, 33%). The median SIBDQ score was 52 (interquartile range, 44 to 59). In UC patients, the stool frequency (β=–2.333, p<0.001), Physician Global Assessment score (β=–3.950, p<0.001), fecal calprotectin level (β=–4.014, p<0.001), and corticosteroid use (β=–4.809, p=0.006) were negatively correlated with the SIBDQ score. In CD patients, the number of diarrhea episodes per day (β=–1.467, p=0.024) and Crohn's Disease Activity Index score (β=–0.045, p<0.001) were negatively correlated with the SIBDQ score. A total of 202 patients completed the second SIBDQ within a mean of 3.4 years. The distributions of SIBDQ score changes were as follows: decrease >10%, 28%; –10%10%, 43%. In both the initial SIBDQ and follow-up SIBDQ, scores for items pertaining to systemic symptoms (tension and fatigue) were relatively low. Conclusions Bowel movement-related problems significantly affect the HRQoL of both UC and CD patients. IBD patients scored lower on SIBDQ items related to general well-being. After 3 years of follow-up at the IBD clinic, 43% of patients showed a significant improvement in HRQoL.