Purpose: One of the novel cell sources of cell-based liver regenerative medicine is human chemically-derived hepatic progenitors (hCdHs). We previously established this cell by direct hepatocyte reprogramming with a combination of small molecules (hepatocyte growth factor, A83-01, CHIR99021). However, there have been several issues concerning the cell’s stability and maintenance, namely the occurrences of epithelial-mesenchymal transition (EMT) that develop fibrotic phenotypes, resulting in the loss of hepatic progenitor characteristics. These hepatic progenitor attributes are thought to be regulated by SOX9, a transcription factor essential for hepatic progenitor cells and cholangiocytes. Methods: To suppress the fibrotic phenotype and improve our long-term hCdHs culture technology, we utilized the epigenetic modulating drugs DNA methyltransferase inhibitor (5-azacytidine) and histone deacetylase inhibitor (sodium butyrate) that have been reported to suppress and revert hepatic fibrosis. To confirm the essential role of SOX9 to our cell, we used clustered regularly interspaced short palindromic repeats-interference (CRISPRi) to repress the SOX9 expression. Results: The treatment of only 5-azacytidine significantly reduces the fibrosis/mesenchymal marker and EMT-related transcription factor expression level in the early passages. Interestingly, this treatment also increased the hepatic progenitor markers expression, even during the reprogramming phase. Then, we confirmed the essential role of SOX9 by repressing the SOX9 expression with CRISPRi which resulted in the downregulation of several essential hepatic progenitor cell markers. Conclusion These results highlight the capacity of 5-azacytidine to inhibit EMT-driven hepatic fibrosis and the significance of SOX9 on hepatic progenitor cell stemness properties.

Colonoscopy is a key procedure for the early detection of colorectal cancer. Despite its importance, the discomfort associated with colonoscopy often requires sedation, and the ideal sedation regimen remains to be determined. In this prospective randomized controlled trial, patients scheduled for colonoscopy were randomly assigned to two different sedation protocols. Group A received a combination of midazolam and propofol, while group B was given midazolam and pethidine. The study analyzed data from 51 patients, with 23 in group A and 28 in group B. The incidence of adverse events was similar across both groups. Additionally, no significant differences were observed in cecal intubation times or total procedure durations. Notably, group A had a lower frequency of required postural changes (1.0±0.7 vs. 1.5±0.7, p=0.02) and a reduced rate of manual compression (52.2% vs. 82.1%, p=0.02). There were no significant differences between the groups regarding subjective pain or overall satisfaction. Both sedation regimens were found to be safe and effective. The midazolam and propofol combination was associated with a smoother procedure, evidenced by fewer postural adjustments and less manual compression needed during colonoscopy.

Background: Skin and soft-tissue defects in the lower legs present significant challenges for surgeons, especially when tendons, bones, or implants are exposed. In such cases, simple dressings or skin grafts are insufficient, necessitating flap surgery.The bipedicled flap is a simpler and more reliable method with a high success rate compared to other flaps, showing minimal flap failures. This study aimed to examine the advantages and limitations of using a bipedicled flap for soft-tissue reconstruction in the lower legs. Methods: This retrospective study reviewed medical records from January 2013 to May 2020, involving 10 bipedicled flaps performed on the lower legs. The study included 5 male and 5 female patients, with an average age of 54.5 years. The defects were due to various causes, including trauma, tumor surgery, postoperative complications such as dehiscence and skin necrosis, and chronic osteomyelitis. The size of the defects ranged from 4 × 3 cm to 16 × 13 cm. The outcomes assessed included flap viability, postoperative complications, and patient satisfaction. Patient satisfaction was assessed on a 15-point scale, evaluating appearance, function, and sensation with up to 5 points each, and categorizing scores as poor (1–3), below average (4–6), average (7–9), good (10–12), and excellent (13–15). Results: All flaps were successfully performed, and there were no cases showing any special complications. Patient satisfaction following the operation was excellent in 3 patients, good in 6 patients, and average in 1 patient, with an overall average score of 11.5 (good) out of 15 among the 10 patients evaluated. Conclusions The bipedicled flap is a simple and secure method for treating soft-tissue defects in the lower legs. Therefore, this technique can be considered as one of the viable options for treating such defects.

The reliability of presepsin as a biomarker of sepsis may be reduced in patients with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT). This study analyzed the utility of plasma presepsin values in predicting mortality in patients with AKI requiring CKRT, particularly those with sepsis-associated AKI. Methods: This single-center retrospective study included 57 patients who underwent CKRT, with plasma presepsin measurements, from April 2022 to March 2023; 35 had sepsis-associated AKI. The predictive values of plasma presepsin, as well as Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, for 28-day mortality were analyzed using receiver operating characteristic curves. Multivariate Cox regression analysis was performed to identify risk factors for 28-day mortality in the sepsis-associated AKI subgroup. Results: Overall, plasma presepsin showed a lower area under the curve value (0.636; 95% confidence interval [CI], 0.491–0.781) than the APACHE II (0.663; 95% CI, 0.521–0.804) and SOFA (0.731; 95% CI, 0.599–0.863) scores did. However, in sepsis-associated AKI, the area under the curve increased to 0.799 (95% CI, 0.653–0.946), which was higher than that of the APACHE II (0.638; 95% CI, 0.450–0.826) and SOFA (0.697; 95% CI, 0.519–0.875) scores. In the multivariate Cox regression analysis, a high presepsin level was an independent risk factor for 28-day mortality in sepsis-associated AKI (hazard ratio, 3.437; p = 0.03). Conclusion: Presepsin is a potential prognostic marker in patients with sepsis-associated AKI requiring CKRT.

Purpose: The aim of this study was to evaluate the accuracy of prostate volume estimates calculated from the ellipsoid formula using the anteroposterior (AP) diameter measured on axial and sagittal images obtained through ultrasonography (US) and magnetic resonance imaging (MRI). Methods: This retrospective study included 456 patients with transrectal US and MRI from two university hospitals. Two radiologists independently measured the prostate gland diameters on US and MRI: AP diameters on axial and sagittal images, transverse, and longitudinal diameters on midsagittal images. The volume estimates, volumeax and volumesag, were calculated from the ellipsoid formula by using the AP diameter on axial and sagittal images, respectively. The prostate volume extracted from MRI-based whole-gland segmentation was considered the gold standard. The intraclass correlation coefficient (ICC) was used to evaluate the inter-method agreement between volumeax and volumesag, and agreement with the gold standard. The Wilcoxon signedrank test was used to analyze the differences between the volume estimates and the gold standard. Results: The prostate gland volume estimates showed excellent inter-method agreement, and excellent agreement with the gold standard (ICCs >0.9). Compared with the gold standard, the volume estimates were significantly larger on MRI and significantly smaller on US (P<0.001). The volume difference (segmented volume–volume estimate) was greater in patients with larger prostate glands, especially on US. Conclusion Volumeax and volumesag showed excellent inter-method agreement and excellent agreement with the gold standard on both US and MRI. However, prostate volume was overestimated on MRI and underestimated on US.

Background: Although pregnant or lactating women have been recognized to be predisposed to de Quervain’s tenosynovitis (DQT), there is a lack of epidemiologic evidence. The purpose of this study was to estimate the nationwide incidence of pregnancy-related DQT (PRDQT) and to analyze risk factors using the Korean National Health Insurance (NHI) database. Methods: A retrospective epidemiologic study of pregnant women in South Korea from 2013 to 2017 was conducted using the NHI claims database. Using corresponding diagnostic codes, we identified women diagnosed with DQT during pregnancy or the postpartum period. We calculated the cumulative incidence and analyzed risk factors such as demographics, pregnancy type, delivery method, gestational complications, and comorbidities using multivariate logistic regression analysis. Results: Between 2013 and 2017, 34,342 patients with PRDQT were identified among 1,601,501 pregnant women, representing a cumulative incidence of approximately 2.1%. Age ≥ 30 years, multiple gestation, cesarean delivery, hypertensive disorders in pregnancy, and underlying rheumatoid arthritis were all identified as significant risk factors for the occurrence of PRDQT, whereas diabetic disorders in pregnancy and underlying diabetes mellitus were not. Conclusions In South Korea, PRDQT was found to affect approximately 2.1 out of 100 pregnant women between 2013 and 2017. The incidence and risk factors identified in this study can be used for clinical consultations and prediction, as well as for development of national health policies.

Background: Although poor oral health is a common comorbidity in individuals with airflow limitation (AFL), few studies have comprehensively evaluated this association. Furthermore, the association between oral health and the severity of AFL has not been well elucidated. Methods: Using a population-based nationwide survey, we classified individuals according to the presence or absence of AFL defined as pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity < 0.7. Using multivariable logistic regression analyses, we evaluated the association between AFL severity and the number of remaining teeth; the presence of periodontitis; the Decayed, Missing, and Filled Teeth (DMFT) index; and denture wearing. Results: Among the 31,839 participants, 14% had AFL. Compared with the control group, the AFL group had a higher proportion of periodontitis (88.8% vs. 79.4%), complete denture (6.2% vs. 1.6%), and high DMFT index (37.3% vs. 27.8%) (P < 0.001 for all). In multivariable analyses, denture status: removable partial denture (adjusted odds ratio [aOR], 1.12; 95% confidence interval [95% CI], 1.04–1.20) and complete denture (aOR, 1.52; 95% CI, 1.01– 2.05), high DMFT index (aOR, 1.13; 95% CI, 1.02–1.24), and fewer permanent teeth (0–19;aOR, 1.32; 95% CI, 1.12–1.52) were significantly associated with AFL. Furthermore, those with severe to very severe AFL had a significantly higher proportion of complete denture (aOR, 2.41; 95% CI, 1.11–3.71) and fewer remaining teeth (0–19; aOR, 2.29; 95% CI, 1.57–3.01). Conclusion Denture wearing, high DMFT index, and fewer permanent teeth are significantly associated with AFL. Furthermore, a reduced number of permanent teeth (0–19) was significantly related to the severity of AFL. Therefore, physicians should pay attention to oral health in managing patients with AFL, such as chronic obstructive pulmonary disease.

Background: Exercise capacity is known to be an independent predictor of cardiovascular events and mortality. However, most previous studies were based on Western populations.Further study is warranted for Asian patients according to ethnic or national standards. We aimed to compare prognostic values of Korean and Western nomograms for exercise capacity in Korean patients with cardiovascular disease (CVD). Methods: In this retrospective cohort study, we enrolled 1,178 patients (62 ± 11 years;78% male) between June 2015 and May 2020, who were referred for cardiopulmonary exercise testing in our cardiac rehabilitation program. The median follow-up period was 1.6 years. Exercise capacity was measured in metabolic equivalents by direct gas exchange method during the treadmill test. The nomogram for exercise capacity from healthy Korean individuals and a previous landmark Western study was used to determine the percentage of predicted exercise capacity. The primary endpoint was the composite of major adverse cardiovascular events (MACE; all-cause death, myocardial infarction, repeat revascularization, stroke and hospitalization for heart failure). Results: A multivariate analysis showed that the risk of primary endpoint was more than double (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.10–4.40) in the patients with lower exercise capacity (< 85% of predicted) by Korean nomogram. The lower exercise capacity was one of the strong independent predictors along with left ventricular ejection fraction, age, and level of hemoglobin. However, the lower exercise capacity by Western nomogram could not predict the primary endpoint (HR, 1.33; 95% CI, 0.85–2.10). Conclusion Korean patients with CVD with lower exercise capacity have higher risk of MACE.Considering inter-ethnic differences in cardiorespiratory fitness, the Korean nomogram provides more suitable reference values than the Western nomogram to determine lower exercise capacity and predict cardiovascular events in Korean patients with CVD.

Purpose: High-dose radiotherapy (RT) for localized prostate cancer requires careful consideration of target position changes and adjacent organs-at-risk (OARs), such as the rectum and bladder. Therefore, daily monitoring of target position and OAR changes is crucial in minimizing interfractional dosimetric uncertainties. For efficient monitoring of the internal condition of patients, we assessed the feasibility of an auto-segmentation of OARs on the daily acquired images, such as megavoltage computed tomography (MVCT), via a commercial artificial intelligence (AI)-based solution in this study. Materials and Methods: We collected MVCT images weekly during the entire course of RT for 100 prostate cancer patients treated with the helical TomoTherapy system. Based on the manually contoured body outline, the bladder including prostate area, and rectal balloon regions for the 100 MVCT images, we trained the commercially available fully convolutional (FC)-DenseNet model and tested its auto-contouring performance. Results: Based on the optimally determined hyperparameters, the FC-DenseNet model successfully auto-contoured all regions of interest showing high dice similarity coefficient (DSC) over 0.8 and a small mean surface distance (MSD) within 1.43 mm in reference to the manually contoured data. With this well-trained AI model, we have efficiently monitored the patient's internal condition through six MVCT scans, analyzing DSC, MSD, centroid, and volume differences. Conclusion We have verified the feasibility of utilizing a commercial AI-based model for auto-segmentation with low-quality daily MVCT images. In the future, we will establish a fast and accurate auto-segmentation and internal organ monitoring system for efficiently determining the time for adaptive replanning.