Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

BACKGROUND: Osteoporosis, characterized by decreased bone mineral density due to an imbalance between osteoblast and osteoclast activity, poses significant challenges in bone healing, particularly in postmenopausal women. Current treatments, such as bisphosphonates, are effective but associated with adverse effects like medication-related osteonecrosis of the jaw, necessitating safer alternatives. METHODS: This study investigated the use of L-serine-incorporated gelatin sponges for bone regeneration in calvarial defects in an ovariectomized rat model of osteoporosis. Thirty rats were divided into three groups: a control group, a group treated with a gelatin sponge containing an amino acid mixture, and a group treated with a gelatin sponge containing L-serine. Bone regeneration was assessed using micro-computed tomography (micro-CT) and histological analyses. RESULTS: The L-serine group showed a significant increase in bone volume (BV) and bone area compared to the control and amino acid groups. The bone volume to total volume (BV/TV) ratio was also significantly higher in the L-serine group.Immunohistochemical analysis demonstrated that L-serine treatment suppressed the expression of cathepsin K, a marker of osteoclast activity, while increasing serine racemase activity. CONCLUSION These findings suggest that L-serine-incorporated gelatin sponges not only enhance bone formation but also inhibit osteoclast-mediated bone resorption, providing a promising and safer alternative to current therapies for osteoporosis-related bone defects. Further research is needed to explore its clinical applications in human patients.

Purpose: The study investigated whether incorporating magnetic resonance imaging (MRI) alongside ultrasonography (US) in the preoperative evaluation is associated with differing survival outcomes between male and female breast cancer patients in a matched analysis. Additionally, clinicopathological prognostic factors were analyzed. Methods: Between January 2005 and December 2020, 93 male and 28,191 female patients who underwent breast surgery were screened. Exact matching analysis was conducted for age, pathologic T and N stages, and molecular subtypes. The clinicopathological characteristics and preoperative imaging methods of the matched cohorts were reviewed. Disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan-Meier analysis, and Cox proportional hazards regression analysis was used to identify prognostic factors. Results: A total of 328 breast cancer patients (61 men and 267 women) were included in the matched analysis. Male patients had worse DFS (10-year DFS, 70.6% vs. 89.2%; P=0.001) and OS (10-year OS, 64.4% vs. 96.3%; P<0.001) than female patients. The pathologic index cancer size (hazard ratio [HR], 2.013; 95% confidence interval [CI], 1.063 to 3.810; P=0.032) was associated with worse DFS, whereas there were no significant factors associated with OS. Adding MRI to US for preoperative evaluation was not associated with DFS (HR, 1.117; 95% CI, 0.223 to 5.583; P=0.893) or OS (HR, 1.529; 95% CI, 0.300 to 7.781; P=0.609) in male patients. Conclusion Adding breast MRI to US in the preoperative evaluation was not associated with survival outcomes in male breast cancer patients, and the pathologic index cancer size was associated with worse DFS.

Purpose: This study aimed to validate pivotal pre-test probability (PTP)-coronary artery disease (CAD) models (CAD consortium model and IJC-CAD model). Materials and Methods: Traditional PTP models-CAD consortium models: two traditional PTP models were used under the CAD consortium framework, namely CAD1 and CAD2. Machine learning (ML)-based PTP models: two ML-based PTP models were derived from CAD1 and CAD2, and used to enhance predictive capabilities [ML-CAD2 and ML-IJC (IJC-CAD)]. The primary endpoint was obstructive CAD. The performance evaluation of these PTP models was conducted using receiver-operating characteristic analysis. Results: The study included 238 participants, among whom 157 individuals (65.9% of the total sample) had CAD. The IJC-CAD model demonstrated the highest performance with an area under the curve (AUC) of 0.860 [95% confidence interval (CI): 0.812– 0.909]. Following this, the ML-CAD2 model exhibited an AUC of 0.814 (95% CI: 0.758–0.870), CAD1 showed an AUC of 0.767 (95% CI: 0.705–0.830), and CAD2 had an AUC of 0.785 (95% CI: 0.726–0.845). Each of the PTP models was adjusted to have a CAD score cutoff that classified cases with a sensitivity of over 95%. The respective cutoff values were as follows: CAD1 and CAD2 >12, MLCAD2 >0.380, and IJC-CAD >0.367. All PTP models achieved a CAD sensitivity of over 95%. Similar to the AUC performance, the accuracy of the PTP models was highest for IJC-CAD, reaching 80.3%. The accuracy of ML-CAD2 was 77.7%, while that for CAD1 and CAD2 was 74.8% and 75.2%, respectively. Conclusion ML-CAD2 and IJC-CAD showed superior performance compared to traditional existing models (CAD1 and CAD2)

Purpose: We investigated the clinical features, current negative-pressure wound therapy (NPWT) management strategies, and outcomes of pelvic-perineal soft tissue infection after open pelvic fractures. Materials and Methods: We analyzed the data of patients admitted to our trauma center with pelvic-perineal soft tissue after open pelvic fractures over a 7-year period. We investigated the injury severity score (ISS), medical costs, number of NPWTs, time required to reach definite wound coverage, complications, fracture classifications, transfusion requirements, interventions, length of stay (LOS) in hospital and intensive care unit (ICU), and prognosis. Results: Twenty patients with open pelvic fractures were treated with NPWT, and one patient who underwent NPWT died of pelvic sepsis during ICU treatment. The median LOS in hospital and medical costs were 98 [56–164] days and 106400 [65600–171100] USD, respectively. Patients treated with instillation NPWT (iNPWT, n=10) had a shorter NPWT duration (24 [13–39] vs. 46 [42–91] days, p=0.023), time to definite wound coverage (30 [21–43] vs. 49 [42–93] days, p=0.026), and hospital LOS (56 [43–72] vs. 158 [101–192] days, p=0.001), as well as lower medical costs (67800 [42500–102500] vs. 144200 [110400–236000] USD, p=0.009) compared to those treated with conventional NPWT. Conclusion NPWT is a feasible method for treating pelvic soft tissue infections in patients with open pelvic fractures. iNPWT can reduce the duration of NPWT, hospital LOS, and medical costs.

Purpose: Cognitive behavioral therapy (CBT) has long been recognized as an effective treatment for depression and suicidality.Virtual reality (VR) technology is widely used for cognitive training for conditions such as anxiety disorder and post-traumatic stress disorder, but little research has considered VR-based CBT for depressive symptoms and suicidality. We tested the effectiveness and safety of a VR-based CBT program for depressive disorders. Materials and Methods: We recruited 57 participants from May 2022 through February 2023 using online advertisements. This multi-center, assessor-blinded, randomized, controlled exploratory trial used two groups: VR treatment group and treat as usual (TAU) group. VR treatment group received a VR mental health training/education program. TAU group received standard pharmacotherapy. Assessments were conducted at baseline, immediately after the 6-week treatment period, and 4 weeks after the end of the treatment period in each group. Results: Depression scores decreased significantly over time in both VR treatment and TAU groups, with no differences between the two groups. The suicidality score decreased significantly only in VR group. No group differences were found in the remission or response rate for depression, perceived stress, or clinical severity. No adverse events or motion sickness occurred during the VR treatment program. Conclusion VR CBT treatment for major depressive disorder has the potential to be equivalent to the gold-standard pharmacotherapy in reducing depressive symptoms, suicidality, and related clinical symptoms, with no difference in improvement found in this study. Thus, VR-based CBT might be an effective alternative to pharmacotherapy for depressive disorders.

Purpose: This study assessed the validity of the hospital standardized mortality ratio (HSMR) risk-adjusted model by comparing models that include clinical information and the current model based on administrative information in South Korea. Materials and Methods: The data of 53976 inpatients were analyzed. The current HSMR risk-adjusted model (Model 1) adjusts for sex, age, health coverage, emergency hospitalization status, main diagnosis, surgery status, and Charlson Comorbidity Index (CCI) using administrative data. As candidate variables, among clinical information, the American Society of Anesthesiologists score, Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) 3, present on admission CCI, and cancer stage were collected. Surgery status, intensive care in the intensive care unit, and CCI were selected as proxy variables among administrative data. In-hospital death was defined as the dependent variable, and a logistic regression analysis was performed. The statistical performance of each model was compared using C-index values. Results: There was a strong correlation between variables in the administrative data and those in the medical records. The C-index of the existing model (Model 1) was 0.785; Model 2, which included all clinical data, had a higher C-index of 0.857. In Model 4, in which APACHE II and SAPS 3 were replaced with variables recorded in the administrative data from Model 2, the C-index further increased to 0.863. Conclusion The HSMR assessment model improved when clinical data were adjusted. Simultaneously, the validity of the evaluation method could be secured even if some of the clinical information was replaced with the information in the administrative data.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Purpose: The purpose of this study was to develop an approach to alleviate the discomfort caused by sandbag compression after a bone marrow examination. This research examined the effects of applying a pressure hemostasis band on bleeding, pain, and discomfort at the bone marrow examination site. Methods: This study was conducted with a nonequivalent control group non-synchronized design. For 74 patients under evaluation who underwent bone marrow examination, sandbag compression was applied to the examination site in the control group (n=37), and a pressure hemostasis band was applied to the intervention group (n=37). In both groups, absolute bed rest was performed for two hours, and bleeding, pain, and discomfort at the examination site were measured. Results: After two hours of the bone marrow examination, there was no difference in bleeding on the gauze between the two groups (F=0.59, p=.444). Bleeding occurred in three patients in the intervention group and six in the control group (χ 2 =1.14, p=.479), with no cases of hematoma detected in either group. One hour post-examination, the control group experienced significantly higher pain (F=5.45, p=.022) and discomfort (F=5.68, p=.020) than the intervention group. However, pain and discomfort levels were similar between groups after two hours. Conclusion Compared to the sandbag compression group, the band application group showed no difference in bleeding and experienced less pain and discomfort at the examination site. This confirms that the pressure hemostasis band is a suitable alternative to sandbag compression in post-examination care.