Purpose: Fertility preservation (FP) is an important issue for young survivors of breast cancer. Although international guidelines recommend pre-treatment fertility counseling for women with breast cancer, there is no standardized protocol or referral system for FP in South Korea. There are also barriers to discussing FP that make patient-centered decision making difficult. This study aimed to develop a shared decision making program for FP and compare the rates of FP procedures between the usual care and shared decision making groups. We hypothesized that multidisciplinary shared decision making for FP would increase the rate of FP procedures and patient satisfaction. Methods The multidisciplinary shared decision making for FP in young women with breast cancer (MYBC) is a multicenter, clustered, stepped-wedge, randomized trial. A total of 1100patients with breast cancer, aged 19–40 years, from nine hospitals in South Korea, will be enrolled. They will be randomized at the institutional level and assigned to usual care and shared decision making groups. Four institutions, each of which can recruit more than 200 patients, will each become a cluster, whereas five institutions, each of which can recruit more than 50 patients, will become one cluster, for a total of five clusters. The shared decision making groups will receive multidisciplinary programs for FP developed by the investigator. The primary outcome is the rate of FP procedures; secondary outcomes include fertility results, satisfaction, and quality of life. Outcomes will be measured at enrollment, treatment initiation, and the 1-, 3-, and 5-year follow-ups after starting breast cancer treatment.Discussion: A multidisciplinary shared decision making program for FP is expected to increase fertility rates and satisfaction among young patients with breast cancer. This study will provide the evidence to implement a multidisciplinary system for patients with breast cancer.

Background: Uveitis is less common in children than in adults; however, pediatric uveitis has a relatively severe disease course that affects the quality of life. Although it is important to understand the epidemiological characteristics of pediatric uveitis, few studies have been conducted in large populations without referral bias. This study investigated the nationwide incidence and prevalence of pediatric uveitis in South Korea according to period, age, anatomic type, and systemic associations. Methods: This nationwide population-based cohort study used data from the Korean National Health Insurance Service from 2002 to 2018. This study included patients younger than 19 years of age with noninfectious uveitis with at least three claims of diagnostic codes of uveitis on separate days with at least once claim of prescription codes of steroid and immunosuppressive agents. All the cases were classified as anterior or non-anterior uveitis, and the overall incidence and prevalence were estimated by age, sex, and period. Patients with noninfectious uveitis were categorized by the presence of associated systemic conditions. Results: A total of 10,862,616 patients over 128,688,078 person-years were evaluated from 2005 to 2016. Overall, 5,368 cases of anterior uveitis and 604 cases of non-anterior uveitis were identified. The incidence and prevalence of pediatric noninfectious uveitis were 4.64 per 100,000 person-years (95% confidence interval [CI], 4.52–4.76) and 8.25 per 100,000 persons (95% CI, 8.09–8.41). Both the incidence and prevalence of pediatric uveitis increased with age. Anterior uveitis accounted for 84.7% of pediatric noninfectious uveitis prevalent cases (6.99 per 100,000 persons). Cases of juvenile idiopathic arthritis (JIA)-associated uveitis accounted for 8.7% (926 cases) of pediatric noninfectious uveitis cases with a prevalence of 0.72 per 100,000 (95% CI, 0.67–0.77). The proportion of systemic associations was higher and JIA-related uveitis accounted for 11.2% (803 cases) of recurrent or chronic noninfectious uveitis cases with a prevalence of 0.62 per 100,000. Conclusion This is the first population-based study investigating the largest population of pediatric patients with uveitis in Korea. The nationwide incidence and prevalence of pediatric noninfectious uveitis in 2005–2016 were 4.64 per 100,000 person-years and 8.25 per 100,000, respectively. The proportion of JIA in pediatric noninfectious uveitis was 8.7%.These population-based study findings provide a better understanding of the public health burden and aid in the planning of health-care strategies for pediatric patients with uveitis.

Purpose: Real-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease (COVID-19) needs to be investigated. Materials and Methods: A retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasone in combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was 30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery. Results: A total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in the dexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinical recovery, compared to the Dexa group (p=0.024). In multivariable analyses, peak FiO2 within 3 days and tocilizumab combination were consistently significant for 30-day recovery (all p<0.05). The DexaToci group showed a significantly steeper decrease in FiO2 (-4.2±2.6) than the Dexa group (−2.7±2.6; p=0.021) by hospital day 15. The duration of oxygen requirement was significantly shorter in the DexaToci group than the Dexa group (median, 10.0 days vs. 17.0 days; p=0.006). Infectious complications and cellular and humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the convalescence stage were not different between the two groups. Conclusion A combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improved clinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2.

In this article, it has been stated that this study was supported by SMtech Development Program (#2018-0006-01) and Research Fund of Chungnam National University (#2017-1794-01). This information has now been corrected as follows: This research was supported by Research Fund of Chungnam National University (#2017-1794-01).

OBJECTIVE: We developed a fully automated smartphone-based stress management application and explored its usability, potential feasibility, and preliminary efficacy for stress management in Korean employees. METHODS: Healthy employees working in large public enterprises were enrolled. Participants used our automated stress management application for four weeks. With the application, they monitored their stress level and life style factors. Personalized stress management techniques, including psychoeducation and cognitive behavioral technique, were also provided based on their stress level and lifestyle pattern. In 2014, additional relaxation techniques were incorporated. Participants’ mental health status and lifestyle pattern were self-assessed at baseline and at 4 weeks after using the application. RESULTS: A total of 68 subjects were recruited. The application generally received high satisfaction rating. After the intervention, perceived stress level was significantly decreased, both in 2013 and 2014 (BEPSI-K score pre. vs. post. 14.27 vs. 11.00, F=12.49, p=0.001 in 2013; 12.05 vs. 10.00, F=17.18, p < 0.001). In 2014, depression symptom severity was also significantly decreased (CES-D score pre- vs. Post-, 17.66 vs. 11.95, F=9.76, p=0.004). The effects were more significant in females and in those < 35 years. CONCLUSION: Our fully automated stress management application is acceptable and usable, showing preliminary efficacy for reducing employees’ stress levels.
Depression ; Female ; Humans ; Life Style ; Mental Health ; Public Sector ; Relaxation Therapy

Minor ginsenosides Rh1 and Rg2 were isolated from Korean red ginseng and reported to have various biological effects on anti-inflammatory and anti-stress activities. However, the effects of Rh1 and Rg2 on antioxidant activity and their regulatory effects on the antioxidant enzymes have not been studied. Since oxidative stress is one of the major toxic inflammatory responses stimulated by lipopolysaccharides (LPS), the present study investigated the role of minor ginsenosides Rh1 and Rg2 on antioxidant effects in LPS-treated RAW 264.7 cells. In this study, we found that treatment with ginsenosides Rh1 and Rg2 strongly inhibited LPS-stimulated intracellular ROS production in cells. Luciferase assay showed that treatment with LPS reduced antioxidant response element (ARE) encoding the pARE-luc promoter activity, while ginsenosides inhibited the pARE-luc promoter activity. Moreover, ginsenosides Rh1 and Rg2 exhibited anti-oxidative activity in LPS-induced cells by upregulating antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Our results suggest that minor ginsenosides Rh1 and Rg2 may be potential bio-active compounds for antioxidative effects by inhibiting the generation of ROS in RAW 264.7 cells.
Antioxidant Response Elements ; Antioxidants ; Catalase ; Ginsenosides* ; Glutathione Peroxidase ; Lipopolysaccharides ; Luciferases ; Oxidative Stress* ; Panax ; RAW 264.7 Cells* ; Reactive Oxygen Species ; Superoxide Dismutase

In the present study, the frequency of research misconduct in Korean medical papers was analyzed using the similarity check software iThenticate®. All Korean papers written in English that were published in 2009 and 2014 in KoreaMed Synapse were identified. In total, 23,848 papers were extracted. 4,050 original articles of them were randomly selected for similarity analysis. The average Similarity Index of the 4,050 papers decreased over time, particularly in 2013: in 2009 and 2014, it was 10.15% and 5.62%, respectively. And 357 (8.8%) had a Similarity Index of ≥ 20%. Authors considered a Similarity Index of ≥ 20% as suspected research misconduct. It was found that iThenticate® cannot functionally process citations without double quotation marks. Papers with a Similarity Index of ≥ 20% were thus individually checked for detecting such text-matching errors to accurately identify papers with suspected research misconduct. After correcting text-matching errors, 142 (3.5% of the 4,050 papers) were suspected of research misconduct. The annual frequency of these papers decreased over time, particularly in 2013: in 2009 and 2014, it was 5.2% and 1.7%, respectively. The decrease was associated with the introduction of CrossCheck by KoreaMed and the frequent use of similarity check software. The majority (81%) had Similarity Indices between 20% and 40%. The fact suggested that low Similarity index does not necessarily mean low possibility of research misconduct. It should be noted that, although iThenticate® provides a fundamental basis for detecting research misconduct, the final judgment should be made by experts.
Duplicate Publication as Topic ; Editorial Policies ; Ethics* ; Judgment ; Periodicals as Topic ; Plagiarism ; Publications* ; Scientific Misconduct ; Synapses

PURPOSE: The aging of society has rapidly progressed, especially in Korea. Therefore, the necessity of research on end-of-life (EOL) care in elderly patients has increased. However, there are few studies on EOL care intensity for non-cancer patients. This study was designed to compare the EOL care intensity between cancer and non-cancer patients. METHODS: We retrospectively analyzed the EOL care intensity based on medical records of decedents of Kyung Hee University Medical Center, a tertiary referral hospital from December 2014 through March 2015. And we compared EOL care intensity between cancer patients and non-cancer patients using statistical analysis of the frequency of invasive procedures and logistic regression analysis for factors that affect the EOL care intensity. RESULTS: Statistical analysis showed invasive procedures, such as intensive care unit admission, endotracheal intubation followed by mechanical ventilation and emergency dialysis, were performed more frequently in non-cancer patients than cancer patients (29.3% vs. 72.4%, P<0.001). And age (P=0.038) and morbidity of cancer (P<0.001) influenced the invasive procedural decision when analyzed by logistic regression analysis. CONCLUSION: The EOL care was more intensive in non-cancer patients, and age and morbidity of cancer were major factors for the treatment intensity.
Academic Medical Centers ; Adult ; Aged ; Aging ; Decision Making ; Dialysis ; Emergencies ; Humans ; Critical Care ; Intensive Care Units ; Intubation, Intratracheal ; Korea ; Logistic Models ; Medical Records ; Respiration, Artificial ; Retrospective Studies ; Terminal Care ; Tertiary Care Centers

The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either CD34+ hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-beta secretion were higher in SDC but CCR7 expression, IFN-gamma and IL-10 secretion were higher in MoDC. The proportion of CD11c+CD8a+ cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-gamma secreting CD8+ T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer.
Animals ; Carcinoma, Lewis Lung ; Dendritic Cells ; Granulocyte-Macrophage Colony-Stimulating Factor ; Hematopoietic Stem Cells ; Interleukin-10 ; Interleukin-12 ; Interleukin-4 ; Lung ; Lung Neoplasms ; Mice ; Monocytes ; Peritoneum ; T-Lymphocytes ; Transforming Growth Factor beta ; Tumor Burden

BACKGROUND: Dendritic cells (DCs) are increasingly being utilized for anti-cancer immunotherapy. Acute myeloid leukemia (AML) blasts are able to generate leukemia-derived DC. Advances in culture techniques and AML-DC characterization justify possible clinical applications. We investigated the ability of AML, acute lymphoblastic leukemia (ALL) and biphenotypic acute leukemia (BAL) blasts to differentiate into DCs in vitro and the qualified function of the leukemia-derived DCs. METHODS: Leukemia cells from 11 patients with AML, 3 patients with ALL and 2 patients with BAL were cultured with GM-CSF, IL-4 and with or without SCF. Cultured leukemia cells were evaluated by phenotype, mixed lymphocyte reaction (MLR), cytokine production and cytotoxic T cell (CTL) inducing activity. RESULTS: DCs were generated with GM-CSF and IL-4 from the leukemic blasts in 72% of the AML patient cells. MHC class I/II, CD11c and ICAM-1 were highly expressed in the AML-derived DCs. MLR and enzyme linked immunospot (ELISPOT) assays demonstrated that AML-DCs were able to induce T cell proliferation and activation into IFN-gamma secreting effector cells. The ALL blasts from two out of three patients differentiated into DCs with MHC class I/II+, CD11c+ only in the presence of GM-CSF, SCF and IL-4 for 14 days. CONCLUSION: These results suggest that functionallyactive DCs can be differentiated from AML blasts using GM-GSF and IL-4 and ALL, BAL blasts were differentiated into DCs only under stem cell-DC culture conditions.
Cell Proliferation ; Culture Techniques ; Dendritic Cells ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunotherapy ; Intercellular Adhesion Molecule-1 ; Interleukin-4 ; Leukemia* ; Leukemia, Biphenotypic, Acute ; Leukemia, Myeloid, Acute ; Lymphocyte Culture Test, Mixed ; Phenotype ; Precursor Cell Lymphoblastic Leukemia-Lymphoma