BACKGROUND: Exogenous Cushing’s syndrome, which results from prolonged glucocorticoid treatment, is associated with metabolic abnormalities. Previously, we reported the inhibitory effect of tonsil-derived mesenchymal stem cell conditioned medium (T-MSC CM) on glucocorticoid signal transduction. In this study, we investigated the therapeutic efficacy of T-MSCs in a mouse model of exogenous Cushing’s syndrome. METHODS: Exogenous Cushing’s syndrome model mice was generated by corticosterone administration in the drinking water for 5 weeks, and T-MSCs were injected intraperitoneally twice during the third week. Serum lipid profiles were measured using a chemistry analyzer. HepG2 cells were treated with dexamethasone and co-cultured with T-MSCs.Expression levels of genes involved in cholesterol metabolism were examined using real-time PCR. Low-density lipoprotein receptor (LDLR) protein levels were determined using western blotting and immunohistochemistry. Liver RNA extracted from the CORT and CORT ? MSC mouse groups was used for transcriptome sequencing analysis and protein– protein interaction analysis. RESULTS: Weight reduction and improvements in dyslipidemia by T-MSC administration were observed only in female mice. T-MSCs reduce circulating LDL cholesterol levels by downregulating liver X receptor a (LXRa) and inducible degrader of LDLR (IDOL) expression, thereby stabilizing LDLRs in the liver. Transcriptome analysis of liver tissue revealed pathways that are regulated by T-MSCs administration. CONCLUSION Administration of MSCs to female mice receiving chronic corticosterone treatment reduced the circulating LDL cholesterol level by downregulating the LXRa–IDOL axis in hepatocytes. These results suggest that T-MSCs may offer a novel therapeutic strategy for managing exogenous Cushing’s syndrome by regulating cholesterol metabolism.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS. Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases. Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression. Conclusion Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

Background: Long-term use of bisphosphonate is a risk factor for atypical femoral fractures (AFFs). Femoral bowing is known to be associated with AFFs. However, whether femoral bowing quickens the occurrence of AFF is unknown. The purpose of this study was to determine whether AFF occurs earlier in patients with severe femoral bowing than in those without severe bowing. Methods: One hundred and sixty-four patients (186 AFFs) from January 2006 to December 2022 were included in this study.According to severity of femoral bowing, patients were divided into 2 groups: severe bowing group (26 femurs) and minimal to moderate bowing group (160 femurs). Age, sex, and completeness and location of AFF were compared between the 2 groups. We compared the time of AFF occurrence after bisphosphonate therapy using cumulative percentage between the 2 groups. Results: Age and sex were similar between the 2 groups, while body mass index (BMI) was lower (22.5 ± 3.0 kg/m 2 vs. 24.5 ± 3.5 kg/m 2 , p = 0.003) in the severe bowing group. The duration of bisphosphonate use was shorter in the severe bowing group than in the minimal to moderate bowing group (3.3 ± 3.8 years vs. 5.0 ± 4.0 years, p = 0.048). In the severe bowing group, 85% of AFFs were diaphyseal in contrast to the 46% in the minimal to moderate bowing group (p < 0.001). Cumulative percentage plot of AFFs in the severe bowing group was left-shifted compared to the minimal to moderate bowing group. Conclusions At the time of AFF diagnosis, the severe bowing group exhibited shorter duration of bisphosphonate use, lower BMI, and a higher incidence of diaphyseal location. Shortening the duration of bisphosphonate therapy may be advisable in patients with severe femoral bowing.

OBJECTIVES: This study aimed to compare maternal outcomes and the home environment between non‑vulnerable families with children under 2 receiving universal home visiting services and vulnerable families receiving sustained home visiting services. METHODS: This study was conducted in Seoul, Korea, where the country’s first nurse‑led early childhood home visiting program was introduced. A total of 551 mother‑child dyads participated in cross‑sectional surveys conducted at various child ages (6±2 weeks, 6±1 months, 12±1 months, and 24±1 months). Universal home visiting services were provided within six weeks postpartum to non‑vulnerable families, while vulnerable families received sustained services consisting of 25 visits over 24 months. Maternal knowledge of sudden infant death syndrome (SIDS) and childcare, maternal distress, and the Korean Infant‑Toddler Home Observation for Measurement of Environment (K‑IT‑HOME) were assessed. RESULTS: Overall, the universal home visitation group demonstrated higher levels of maternal knowledge regarding SIDS and childcare compared to the sustained home visitation group (all p-values <0.05), while the sustained home visitation group reported higher levels of maternal distress (p<0.001). The total K‑IT‑HOME score was 1.47 points higher in the universal home visitation group than in the sustained home visitation group (p<0.001). No significant differences were observed in the acceptance, organization, or involvement subscales of the K‑IT‑HOME (all p-values >0.05). CONCLUSIONS This study demonstrated that disparities in maternal outcomes and home environments persisted in early childhood between the sustained and universal home visitation groups.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.