Purpose: This 6-year post-marketing surveillance (PMS) study was conducted in South Korea to evaluate the real-world safety and effectiveness of eribulin in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Materials and Methods: During the study period (17 August 2012 to 16 August 2018), case-report files (CRFs) of patients receiving eribulin were collected. The main study endpoint was to assess the safety of eribulin. Evaluation of the effectiveness of eribulin was an exploratory endpoint. Patients were followed for 1 year after eribulin initiation. Results: CRFs were collected from 64 investigators at 64 sites for 1,079 patients. The safety analysis set (SAS) included 1,001 eribulin recipients; effectiveness was assessed in 244 patients. In the SAS, patients were predominantly female (99.6%), with a median age of 53.0 years, and diagnosed with metastatic breast cancer (92.0%). Eribulin was administered as a median 4th line chemotherapy. A total of 2,124 treatment-emergent adverse events (TEAEs) were reported in 661 patients (66.0%). Neutropenia was the most common TEAE (32.5% of patients), occurring at a median of 9-11 days from initial eribulin administration. Overall response and disease control rates were 31.7% and 95.6%, respectively, and the median duration of eribulin use (time to treatment failure) was 3.0 months. Conclusion This large real-world PMS analysis in patients with advanced or metastatic breast cancer demonstrated the effectiveness of eribulin and found no new safety concerns relative to safety information from prior clinical and real-world studies, and approvals in South Korea and other countries.

Background: Despite various therapeutic modalities for keloids have been introduced; however, their therapeutic effects are limited. Therefore, the development of a new approach for inhibiting collagen production by scar fibroblasts is needed. Objective: To investigate the effect of electrical stimulation using a low-frequency and low-intensity alternating current on collagen and MMP-1 levels in human dermal fibroblasts. Methods: Low-frequency (20 kHz) and low-intensity (1 V/cm) electrical stimulations were applied to primary dermal fibroblasts. The production of type I procollagen and expression of matrix metalloproteinase-1 were evaluated. Transcriptomic analyses were conducted to explore the possible modes of action of electrical stimulation. Results: Electrical stimulation effectively suppressed type I procollagen production and increased MMP-1 expression. In addition, transcriptomic analyses revealed that electrical stimulation altered the gene expression associated with membrane permeability and the structure of cellular membranes. Validation using real-time polymerase chain reaction revealed that electrical stimulation significantly altered the expression of mechanosensitive ion channels (PIEZO2) and membrane-bound protein organizing caveolae (CAVIN2). Conclusion Electrical stimulation using low-frequency and low-intensity alternating currents effectively modulates extracellular matrix homeostasis by altering the cellular membrane structure and function. Our findings suggest a promising therapeutic approach for the management of keloids and hypertrophic scars.

PURPOSE: . This in vitro study aimed to compare the accuracy of the conventional facebow system and the newly developed POP (PNUD (Pusan National University Dental School) Occlusal Plane) bow system for occlusal plane transfer in asymmetric ear position. MATERIALS AND METHODS: . Two dentists participated in this study, one was categorized as Experimenter 1 and the other as Experimenter 2 based on their clinical experience with the facebow (1F, 2F) and POP bow (1P, 2P) systems. The vertical height difference between the two ears of the phantom model was set to 3 mm. Experimenter 1 and Experimenter 2performed the facebow and POP bow systems on the phantom model 10 times each, and the transfer accuracy was analyzed. The accuracy was evaluated by measuring the angle between the reference virtual plane (RVP) of the phantom model and the experimental virtual plane (EVP) of the upper mounting plate through digital superimposition. All data were statistically analyzed using a paired t-test (P < .05). RESULTS: . Regardless of clinical experience, the POP bow system (0.53° ± 0.30 (1P) and 0.19° ± 0.18 (2P) for Experimenter 1 and 2, respectively) was significantly more accurate than the facebow system (1.88° ± 0.50 (1F) and 1.34° ± 0.25 (2F), respectively) in the frontal view (P < .05). In the sagittal view, no significant differences were found between the POP bow system (0.92° ± 0.50 (1P) and 0.73° ± 0.42 (2P) for Experimenter 1 and 2, respectively) and the facebow system (0.82° ± 0.49 (1F) and 0.60° ± 0.39 (2F), respectively), regardless of clinical experience (P > .05). CONCLUSION . In cases of asymmetric ear position, the POP bow system may transfer occlusal plane information more accurately than the facebow system in the frontal view, regardless of clinical experience.

Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/ NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.

Background: Self-harm is an important public health problem with increasing incidences among adolescents for over a decade. This study aimed to identify factors associated with self-harm in adolescent psychiatric inpatients in Korea. We also investigated clinical characteristics associated with nonsuicidal self-injury disorder (NSSI-D) and suicidal behavior disorder (SBD) according to the Diagnostic and Statistical Manual of Mental Disorders 5 criteria. Methods: This retrospective study included 215 adolescents aged between 12 to 18 years, who were admitted to the psychiatric ward of Samsung Medical Center, Seoul, Korea, from January 2014 to February 2021. Participants were divided into three groups according to NSSI-D and SBD diagnostic criteria. Collected data were analyzed using chi-square test and analysis of variance test. Results: Overall, 57.7% of the participants (n=124) reported self-harm at least once in their lives. Patients with self-harm were more likely to have experienced parental conflict, parent-child relational problems, and verbal, physical, or sexual abuse. Among the three groups divided according to NSSI-D and SBD diagnostic criteria, patients with both NSSI-D and SBD were more likely to have experienced parent-child relational problems than those with either NSSI-D only or SBD only. Conclusion This study shows that parent-child relational problem is associated with high incidences of selfharm. Especially, the parent-child relational problem seemed to be a risk factor for SBD among patients with NSSI-D. These are important findings that provide an understanding of the self-harm characteristics and therefore improve prevention and treatment strategies in psychiatric adolescent patients.

Purpose: Mesenchymal-epithelial transition tyrosine kinase receptor (MET) amplification is one of the common acquired resistance mechanisms to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). To evaluate the usefulness of screening methods for MET status, we studied the impact of MET amplification or protein overexpression in EGFR-mutant non-small cell lung cancer patients who were treated with EGFR TKI. Methods: A total of 214 patients treated with EGFR TKI as first-line therapy with available tissue biopsy was analyzed. Paired biopsies were obtained from 111 patients at baseline and at onset of resistance. MET status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results: Among 111 patients with paired samples, incidence of MET alteration was increased according to both MET overexpression by IHC (14.4% to 22.5%) and MET amplification by FISH (1.8% to 8.1%) with moderated to strong IHC intensity samples after EGFR TKI treatment. In patients treated with 1st-generation EGFR TKI, MET amplification by FISH was significantly related to shorter progression-free survival (P=0.04) and overall survival (P=0.01). In contrast, there was no difference in clinical outcomes according to MET intensity of IHC. Patients harboring MET amplification by FISH were associated with poor clinical outcomes compared to those with T790M mutation at progression. Conclusion These results suggest that FISH is more informative than IHC for identification of patients with MET amplification as an EGFR TKI resistance mechanism. Given the poor outcome in patients who developed MET amplification, combinational trials with more active MET inhibitor are needed to overcome resistance.

Objective: This study aimed to determine the tic aggravation event rate and cumulative incidence rate in the use of methylphenidate (MPH) treatment in attention-deficit/hyperactivity disorder (ADHD) and the factors that influence tic aggravation. Methods: We conducted a retrospective chart review of children and adolescents aged between 6 to 15 years, who were diagnosed with ADHD from January 2017 to December 2019. A total of 121 subjects were included. The MPH dosage, psychiatric family history, comorbidity and past history of tics were assessed through chart review and the psychological examinations data were included. Collected data were analyzed using Cox regression and Kaplan-Meier survival analysis. Results: Tic aggravation event rates without a past history of tics were 2.9% with MPH treatment in ADHD. Past history of tics, total MPH dosage and age were the factors associated with tic aggravation ([HR 21.46, p<0.001], [HR 0.94, p=0.023], [HR 0.79, p=0.021] for each). Cumulative incidence of tic aggravation was different between groups with or without past tic history. When treated with MPH, all tic aggravation appeared within approximately eight months but for subjects with a past history of tic, aggravation showed within approximately six months (p<0.001). Conclusion Tic aggravation event rate was significantly low especially in the group without a past history of tics with the use of MPH in ADHD. However, a thorough assessment of past history of tics, and close monitoring during the first six-eight months of treatment with MPH is needed to avert a potential worsening of tics.

Objective: This study aimed to determine the tic aggravation event rate and cumulative incidence rate in the use of methylphenidate (MPH) treatment in attention-deficit/hyperactivity disorder (ADHD) and the factors that influence tic aggravation. Methods: We conducted a retrospective chart review of children and adolescents aged between 6 to 15 years, who were diagnosed with ADHD from January 2017 to December 2019. A total of 121 subjects were included. The MPH dosage, psychiatric family history, comorbidity and past history of tics were assessed through chart review and the psychological examinations data were included. Collected data were analyzed using Cox regression and Kaplan-Meier survival analysis. Results: Tic aggravation event rates without a past history of tics were 2.9% with MPH treatment in ADHD. Past history of tics, total MPH dosage and age were the factors associated with tic aggravation ([HR 21.46, p<0.001], [HR 0.94, p=0.023], [HR 0.79, p=0.021] for each). Cumulative incidence of tic aggravation was different between groups with or without past tic history. When treated with MPH, all tic aggravation appeared within approximately eight months but for subjects with a past history of tic, aggravation showed within approximately six months (p<0.001). Conclusion Tic aggravation event rate was significantly low especially in the group without a past history of tics with the use of MPH in ADHD. However, a thorough assessment of past history of tics, and close monitoring during the first six-eight months of treatment with MPH is needed to avert a potential worsening of tics.

Purpose: The purpose of this study was to measure the cancer detection rate of computer-aided detection (CAD) software in preoperative automated breast ultrasonography (ABUS) of breast cancer patients and to determine the characteristics associated with false-negative outcomes. Methods: A total of 129 index lesions (median size, 1.7 cm; interquartile range, 1.2 to 2.4 cm) from 129 consecutive patients (mean age±standard deviation, 53.4±11.8 years) who underwent preoperative ABUS from December 2017 to February 2018 were assessed. An index lesion was defined as a breast cancer confirmed by ultrasonography (US)-guided core needle biopsy. The detection rate of the index lesions, positive predictive value (PPV), and false-positive rate (FPR) of the CAD software were measured. Subgroup analysis was performed to identify clinical and US findings associated with false-negative outcomes. Results: The detection rate of the CAD software was 0.84 (109 of 129; 95% confidence interval, 0.77 to 0.90). The PPV and FPR were 0.41 (221 of 544; 95% CI, 0.36 to 0.45) and 0.45 (174 of 387; 95% CI, 0.40 to 0.50), respectively. False-negative outcomes were more frequent in asymptomatic patients (P<0.001) and were associated with the following US findings: smaller size (P=0.001), depth in the posterior third (P=0.002), angular or indistinct margin (P<0.001), and absence of architectural distortion (P<0.001). Conclusion The CAD software showed a promising detection rate of breast cancer. However, radiologists should judge whether CAD software-marked lesions are true- or false-positive lesions, considering its low PPV and high FPR. Moreover, it would be helpful for radiologists to consider the characteristics associated with false-negative outcomes when reading ABUS with CAD.

Purpose: This study aimed to predict a heavy nodal burden (≥3 metastatic axillary lymph nodes [LNs]) using axillary ultrasonography (US) and US-guided fine-needle aspiration biopsy (FNAB) in patients with early-stage breast cancer. Methods: We retrospectively reviewed the medical records of 403 women (404 cancers) who underwent US-guided FNAB for axillary LN staging from January 2006 to December 2015. US findings and US-guided FNAB results were reviewed and compared using pathology results as the reference. Diagnostic performance was analyzed, and clinicopathological and radiological findings were compared between patients with <3 metastatic LNs and ≥3 metastatic LNs. Results: The final pathology results revealed that 20.5% of cancers had heavy nodal metastases. US-guided FNAB showed significantly higher sensitivity (79.0% vs. 63.0%, P=0.009) and specificity (84.8% vs. 79.3%, P=0.036) in predicting heavy nodal metastases than did US. The presence of a larger number of suspicious LNs (two or more) on axillary US and positive FNAB results were significantly correlated with a heavy nodal burden in the multivariate analysis. The odds ratios were 4.20 (95% confidence interval [CI], 1.90 to 9.39) for two suspicious LNs, 9.40 (95% CI, 2.99 to 29.54) for three or more suspicious LNs, and 14.22 (95% CI, 6.78 to 29.82) for positive FNAB results. Conclusion The number of suspicious LNs detected on axillary US and FNAB results can help predict a heavy axillary nodal burden in patients with early-stage breast cancer.