Background: Tacrolimus is a key immunosuppressant after liver transplantation.Although guideline-recommended trough levels are 4–10 ng/mL, concerns about nephrotoxicity, metabolic complications, and malignancies have led to interest in minimizing tacrolimus use. However, the effects of lower tacrolimus levels on graft rejection and hepatocellular carcinoma (HCC) recurrence remain unclear. Methods: We conducted a single-center, retrospective study of adult patients (≥19 years) who underwent living donor liver transplantation between January 2000 and December 2021. Patients were divided into low tacrolimus (FK) (<6 ng/mL) and high FK (≥6 ng/mL) groups based on tacrolimus levels measured 1–2 years post-transplantation. We analyzed overall survival, biopsy-proven rejection-free survival, and HCC recurrence-free survival in relevant subgroups. Cox proportional hazards regression identified predictors of mortality, rejection, and HCC recurrence. Results: Among 1,117 recipients, 941 were in the low FK group and 176 in the high FK group. Landmark analysis showed significantly better 10-year overall survival in the low FK group (82.8% vs. 68.8%, p=0.016), while rejection-free survival did not differ significantly beyond 2 years (p=0.098), despite early separation favoring the low FK group (p<0.001). Higher tacrolimus levels independently predicted increased mortality (hazard ratio [HR]=1.98, 95% confidence interval [CI] 1.35–2.89; p<0.001) and rejection (HR=2.20, 95% CI 1.48–3.27; p<0.001). Among 614 HCC patients, landmark analysis revealed no significant difference in recurrence-free survival (77.7% vs. 81.2%, p=0.288) or overall survival (77.3% vs. 65.8%, p=0.215), and FK levels were not independently associated with either outcome. Conclusion Maintaining tacrolimus levels below 6 ng/mL was associated with better survival and rejection outcomes without increasing HCC recurrence, suggesting dose minimization may be feasible in selected patients.

Purpose: Photobiomodulation (PBM), encompassing low-energy laser treatment and light-emitting diode (LED) phototherapy, has demonstrated positive impacts on skin rejuvenation and wound healing. Organic light-emitting diodes (OLEDs) present a promising advancement as wearable light sources for PBM. However, the biological and biochemical substantiation of their skin rejuvenation and wound healing effects remains limited. This study aimed to ascertain the safety and efficacy of OLEDs as a nextgeneration PBM modality through comprehensive in vitro and in vivo investigations. Materials and Methods: Cell viability assays and human ex vivo skin analyses were performed after exposure to OLED and LED irradiation to examine their safety. Subsequent evaluations examined expression levels and wound healing effects in human dermal fibroblasts (HDFs) using quantitative reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and wound healing assays post-irradiation. Additionally, an in vivo study was conducted using a ultra violet (UV)-irradiated animal skin model to explore the impact of OLED exposure on dermal collagen density and wrinkles, employing skin replica and tissue staining techniques. Results: OLED irradiation had no significant morphological effects on human skin tissue, but caused a considerably higher expression of collagen than the control and LED-treated groups. Moreover, OLED irradiation reduced the expression levels of matrix metalloproteinases (MMPs) more effectively than did LED on HDFs. OLED irradiation group in HDFs had significantly higher expression levels of growth factors compared to the control group, but similar to those in the LED irradiation group. In addition, OLED irradiation on photo-aged animal skin model resulted in increased collagen fiber density in the dermis while reducing ultra violet radiation-mediated skin wrinkles and roughness, as shown in the skin replica. Conclusion This study established comparable effectiveness between OLED and LED irradiation in upregulating collagen and growth factor expression levels while downregulating MMP levels in vitro. In the UV-irradiated animal skin model, OLED exposure post UV radiation correlated with reduced skin wrinkles and augmented dermal collagen density. Accelerated wound recovery and demonstrated safety further underscore OLEDs’ potential as a future PBM modality alongside LEDs, offering promise in the realms of skin rejuvenation and wound healing.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background/Aims: This study investigated whether the personality traits of endoscopists are associated with the effect of interventions for the improvement of colonoscopy quality. Methods: This prospective, multicenter, single-blind study was performed with 13 endoscopists in three health screening centers over a 12-month period. Quality indicators (QIs), including adenoma detection rate (ADR), polyp detection rate (PDR), and withdrawal time, were measured every 3 months. Consecutive interventions for the improvement of colonoscopy quality were conducted every 3 months, which included the personal notification of QIs, the in-group notification of QIs, and finally a targeted “quality education” session. The personality traits of each endoscopist were evaluated for perfectionism, fear of negative evaluation, and cognitive flexibility after the last QI assessment. Results: A total of 4,095 colonoscopies were evaluated to measure the QIs of the individual endoscopists for 12 months. The mean ADR, PDR, and withdrawal time of the 13 endoscopists were 32.3%, 47.7%, and 394 seconds at baseline and increased to 39.0%, 55.1%, and 430 seconds by the end of the study (p=0.003, p=0.006, and p=0.004, respectively). Among the three interventions, only quality education significantly improved QIs: ADR, 36.0% to 39.0% (odds ratio, 1.28; 95% confidence interval, 1.01 to 1.63). The improvement of ADR and PDR by education was significantly associated with perfectionism (r=0.617, p=0.033 and r=0.635, p=0.027, respectively) and fear of negative evaluation (r=0.704, p=0.011 and r=0.761, p=0.004, respectively). Conclusions Education can improve colonoscopy quality, and its effect size is associated with an endoscopist’s personal traits such as perfectionism and fear of negative evaluation (ClinicalTrials.gov Registry NCT03796169).

Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.