Background: s/Aims: While large-for-size syndrome is uncommon in liver transplantation (LT), it can result in fatal outcome. To prevent such fatality, we manufactured 3D-printed intra-abdominal cavity replicas to provide intuitive understanding of the sizes of the graft and the patient’s abdomen in patients with small body size between July 2020 and February 2022. Methods: Clinical outcomes were compared between patients using our 3D model during LT, and patients who underwent LT without 3D model by using 1 : 5 ratio propensity score-matched analysis. Results: After matching, a total of 20 patients using 3D-printed abdominal cavity model and 100 patients of the control group were included in this study. There were no significant differences in 30-day postoperative complication (50.0% vs. 64.0%, p = 0.356) and the incidence of large-for-size syndrome (0% vs. 7%, p = 0.599). Overall survival of the 3D-printed group was similar to that of the control group (p = 0.665), but graft survival was significantly superior in the 3D-printed group, compared to the control group (p = 0.034). Conclusions Since it showed better graft survival, as well as low cost and short production time, our 3D-printing protocol can be a feasible option for patients with small abdominal cavity to prevent large-for-size syndrome after LT.

Purpose: Common bile duct (CBD) stone recurrence after laparoscopic CBD exploration (LCBDE) is relatively common. No studies have been conducted evaluating the safety and feasibility of re-do LCBDE in the treatment of recurrent CBD stones. Methods: This single-center retrospective study reviewed 340 consecutive patients who underwent LCBDE for CBD stones between January 2004 and December 2020. Patients with pancreatobiliary malignancies and those who underwent other surgical procedures were excluded. Results: Of the 340 included patients, 45 experienced a recurrence after a mean follow-up period of 24.2 months. Of them, 18 underwent re-do LCBDE, 20 underwent endoscopic intervention, 2 underwent radiologic intervention, and 5 underwent observation. Re-do LCBDE and initial LCBDE showed similar surgical outcomes in terms of operative time (113.1 minutes vs. 107.5 minutes, P = 0.515), estimated blood loss (42.5 mL vs. 49.1 mL, P = 0.661), open conversion rate (2.9% vs. 0%, P = 0.461), postoperative complication (15.3% vs. 22.2%, P = 0.430), and postoperative hospital stay (6.5 days vs. 6.4 days, P = 0.921). Comparing re-do LCBDE and nonsurgical treatment (endoscopic or radiologic), no statistically significant differences were noted in posttreatment complication (22.2% vs. 13.6%, P = 0.477), hospital stay (6.4 days vs.7.3 days, P = 0.607), and recurrence (50.0% vs. 36.4%, P = 0.385). The clearance rate was higher in the re-do LCBDE group than in the nonsurgical group (100% vs. 81.8%, P = 0.057). Conclusion Compared to initial LCBDE and endoscopic or radiological treatments, re-do LCBDE for recurrent CBD stones is a treatment option worth considering in selected patients.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups. Materials and Methods: A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease. Results: Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment. Conclusion HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

Objective: To assess the feasibility of ultrafast brain magnetic resonance imaging (MRI) in pediatric patients. Materials and Methods: We retrospectively reviewed 194 pediatric patients aged 0 to 19 years (median 10.2 years) who underwent both ultrafast and conventional brain MRI between May 2019 and August 2020. Ultrafast MRI sequences included T1 and T2-weighted images (T1WI and T2WI), fluid-attenuated inversion recovery (FLAIR), T2*-weighted image (T2*WI), and diffusion-weighted image (DWI). Qualitative image quality and lesion evaluations were conducted on 5-point Likert scales by two blinded radiologists, with quantitative assessment of lesion count and size on T1WI, T2WI, and FLAIR sequences for each protocol. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) analyses were used for comparison. Results: The total scan times for equivalent image contrasts were 1 minute 44 seconds for ultrafast MRI and 15 minutes 30 seconds for conventional MRI. Overall, image quality was lower in ultrafast MRI than in conventional MRI, with mean quality scores ranging from 2.0 to 4.8 for ultrafast MRI and 4.8 to 5.0 for conventional MRI across sequences (P < 0.001 for T1WI, T2WI, FLAIR, and T2*WI for both readers; P = 0.018 [reader 1] and 0.031 [reader 2] for DWI). Lesion detection rates on ultrafast MRI relative to conventional MRI were as follows: T1WI, 97.1%; T2WI, 99.6%; FLAIR, 92.9%; T2*WI, 74.1%; and DWI, 100%. The ICC (95% confidence interval) for lesion size measurements between ultrafast and conventional MRI was as follows: T1WI, 0.998 (0.996–0.999); T2WI, 0.998 (0.997–0.999); and FLAIR, 0.99 (0.985–0.994). Conclusion Ultrafast MRI significantly reduces scan time and provides acceptable results, albeit with slightly lower image quality than conventional MRI, for evaluating intracranial abnormalities in pediatric patients.

Objective: To assess the feasibility of ultrafast brain magnetic resonance imaging (MRI) in pediatric patients. Materials and Methods: We retrospectively reviewed 194 pediatric patients aged 0 to 19 years (median 10.2 years) who underwent both ultrafast and conventional brain MRI between May 2019 and August 2020. Ultrafast MRI sequences included T1 and T2-weighted images (T1WI and T2WI), fluid-attenuated inversion recovery (FLAIR), T2*-weighted image (T2*WI), and diffusion-weighted image (DWI). Qualitative image quality and lesion evaluations were conducted on 5-point Likert scales by two blinded radiologists, with quantitative assessment of lesion count and size on T1WI, T2WI, and FLAIR sequences for each protocol. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) analyses were used for comparison. Results: The total scan times for equivalent image contrasts were 1 minute 44 seconds for ultrafast MRI and 15 minutes 30 seconds for conventional MRI. Overall, image quality was lower in ultrafast MRI than in conventional MRI, with mean quality scores ranging from 2.0 to 4.8 for ultrafast MRI and 4.8 to 5.0 for conventional MRI across sequences (P < 0.001 for T1WI, T2WI, FLAIR, and T2*WI for both readers; P = 0.018 [reader 1] and 0.031 [reader 2] for DWI). Lesion detection rates on ultrafast MRI relative to conventional MRI were as follows: T1WI, 97.1%; T2WI, 99.6%; FLAIR, 92.9%; T2*WI, 74.1%; and DWI, 100%. The ICC (95% confidence interval) for lesion size measurements between ultrafast and conventional MRI was as follows: T1WI, 0.998 (0.996–0.999); T2WI, 0.998 (0.997–0.999); and FLAIR, 0.99 (0.985–0.994). Conclusion Ultrafast MRI significantly reduces scan time and provides acceptable results, albeit with slightly lower image quality than conventional MRI, for evaluating intracranial abnormalities in pediatric patients.