Background: Chromosomal alterations serve as diagnostic and prognostic markers in acute leukemia. Given the evolving landscape of chromosomal abnormalities in acute leukemia, we previously studied these over two periods. In this study, we investigated the frequency of these abnormalities and clinical trends in acute leukemia in Korea across three time periods. Methods: We retrospectively analyzed data from 1,787 patients with acute leukemia (319 children and 1,468 adults) diagnosed between 2006 and 2020. Conventional cytogenetics, FISH, and multiplex quantitative PCR were used for analysis. The patient groups were divided according to the following three study periods: 2006–2009 (I), 2010–2015 (II), and 2016–2020 (III). Results: Chromosomal aberrations were detected in 92% of patients. The PML::RARA translocation was the most frequent. Over the 15-yr period, chromosomal aberrations showed minimal changes, with specific fusion transcripts being common among patients.ALL was more prevalent in children than in adults and correlated significantly with the ETV6::RUNX1 and RUNX1::RUNX1T1 aberrations. The incidence of ALL increased during the three periods, with PML::RARA remaining common. Conclusions The frequency of chromosomal abnormalities in acute leukemia has changed subtly over time. Notably, the age of onset of adult AML has continuously increased. Our results may help in establishing diagnoses and clinical treatment strategies and developing various molecular diagnostic platforms.

Background/Aims: Peroral cholangioscopy (POC) has been used to assess intrahepatic duct (IHD) lesions but with a limited role. A new multibending (MB) ultraslim endoscope has been designed to improve POC performance. We evaluated the usefulness of POC using the MB ultraslim endoscope for the management of IHD lesions. Methods: Between March 2017 and March 2020, 22 patients underwent direct POC using the MB ultraslim endoscope for IHD lesions documented by previous imaging or cholangiopancreatography. The primary outcome was technical success of POC, and secondary outcomes were technical success of POC-guided interventions, median procedure time, and POC-related adverse events. Results: The technical success rate for POC using the MB ultraslim endoscope for IHD lesions was 95.5% (21/22). Free-hand insertion was successful in 95.2% (20/21). The overall technical success rate for POC-guided intervention was 100% (21/21), including nine diagnostic and 12 therapeutic procedures (eight direct stone removal and four intraductal lithotripsies). The median procedure time was 29 minutes (range, 9 to 79 minutes). There were no procedure-related adverse events. Conclusions Direct POC using the MB ultraslim endoscope allows direct visualization of IHD lesions and may be useful for diagnosis and therapeutic management in selected patients.

Background: The risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance. Methods: The SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patientoriented composite outcome (POCO) at 2 years. Results: Patient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group.Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel.Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487–3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663–3.012,P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups. Conclusion With meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES.

Background/Aims: Treatment options for difficult bile duct stones are limited. Direct peroral cholangioscopy (POC)-guided lithotripsy may be an option. A newly developed multibending (MB) ultraslim endoscope has several structural features optimized for direct POC. We evaluated the utility of direct POC using an MB ultraslim endoscope for lithotripsy in patients with difficult bile duct stones. Methods: Twenty patients with difficult bile duct stones, in whom stone removal using conventional endoscopic methods, including mechanical lithotripsy, had failed were enrolled from March 2018 to August 2019. Direct POC-guided lithotripsy was performed by electrohydraulic lithotripsy or laser lithotripsy. The primary outcome was complete ductal clearance, defined as the retrieval of all bile duct stones after lithotripsy confirmed by balloon-occluded cholangiography and/or direct POC. Results: The technical success rate of direct POC was 100% (20/20), and the free-hand insertion rate was 95% (19/20). Direct POC-guided lithotripsy, attempted by electrohydraulic lithotripsy in nine patients (45%) and laser lithotripsy in 11 patients (55%), was successful in 95% (19/20) of the patients. Complete ductal clearance after direct POC-guided lithotripsy was achieved in 95% (19/20) of patients. Patients required a median of 2 (range, 1–3) endoscopic retrograde cholangiopancreatography sessions for complete stone removal. Adverse event was observed in one patient (5%) with hemobilia and was treated conservatively. Conclusions Direct POC using an MB ultraslim endoscope was safe and effective for lithotripsy in patients with difficult bile duct stones.

Background and Objectives: Brain organoids have the potential to improve our understanding of brain development and neurological disease. Despite the importance of brain organoids, the effect of vascularization on brain organoids is largely unknown. The objective of this study is to develop vascularized organoids by assembling vascular spheroids with cerebral organoids. Methods: and Results: In this study, vascularized spheroids were generated from non-adherent microwell culture system of human umbilical vein endothelial cells, human dermal fibroblasts and human umbilical cord blood derived mesenchymal stem cells. These vascular spheroids were used for fusion with iPSCs induced cerebral organoids. Immunostaining studies of vascularized organoids demonstrated well organized vascular structures and reduced apoptosis. We showed that the vascularization in cerebral organoids up-regulated the Wnt/β-catenin signaling. Conclusions We developed vascularized cerebral organoids through assembly of brain organoids with vascular spheroids. This method could not only provide a model to study human cortical development but also represent an opportunity to explore neurological disease.

Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative is a rare myeloid neoplasm, especially in pediatric patients. The mutations identified in aCML have overlapped with those of other myeloid neoplasms. In recent studies, ruxolitinib, a Janus kinase (JAK) inhibitor, was found efficient in some patients of aCML with CSF3R mutation. Here, we report a pediatric case of aCML with CSF3Rmutation who did not respond to ruxoritinib, but was successfully rescued with hematopoietic stem cell transplantation (SCT). A stuporous 13-year-old boy was transferred with leukocytosis.Computed tomography showed an acute lobar intracranial hemorrhage in the left frontal lobe. The bone marrow aspirate demonstrated significant granulocytic proliferations with predominant dysplasia. Hydroxyurea and imatinib were initially administered to reduce leukocytosis. After BCR-ABL1 was found to be negative, imatinib was discontinued. After the identification of CSF3R mutation by customized targeted DNA sequencing (NGeneBio, Seoul, South Korea), ruxolitinib was added. He seemed to have hematologic and clinical responses on 2 months of ruxolitinib treatment, but the blast counts in the bone marrow increased. He underwent a full-matched unrelated peripheral blood SCT successfully 3 months after his diagnosis and has currently been disease-free 8 months since the transplantation. In conclusion, ruxolitinib for aCML with CSF3R mutation might not always induce a significant response but could be used as bridge to hematopoietic SCT.

Background: The healthcare workers (HCWs) were exposed to never-experienced psychological distress during the early stage of the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to investigate how the COVID-19 pandemic affected the mental health of HCWs during the hospital lockdown period due to mass healthcare-associated infection during the early spread of COVID-19. Methods: A real-time online survey was conducted between April 14–18, 2020 among HCWs who worked at the university hospital where COVID-19 was confirmed in a patient, and the hospital was shut down for 3 weeks. Along with demographic variables and work-related information, psychological distress was measured using the Generalized Anxiety Disorder-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), the Maslach Burnout Inventory-General Survey scale, and the Stress and Anxiety to Viral Epidemics-9. Results: The HCWs working in the cohort ward and those who have experienced social discrimination had significantly higher level of depression (PHQ-9 score; 5.24 ± 4.48 vs. 4.15 ± 4.38; P < 0.01 and 5.89 ± 4.78 vs. 3.25 ± 3.77; P < 0.001, respectively) and anxiety (GAD-7 score; 3.69 ± 3.68 vs. 2.87 ± 3.73;P < 0.05 and 4.20 ± 4.22 vs. 2.17 ± 3.06; P < 0.001, respectively) compared to other HCWs. Worries regarding the peer relationship and the skepticism about job were associated with depression (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.07–1.79; P < 0.05 and OR, 1.69; 95% CI, 1.31–2.17; P < 0.001, respectively) and anxiety (OR, 1.73; 95% CI, 1.21–2.49; P < 0.01 and OR, 1.54; 95% CI, 1.09–2.17; P < 0.05, respectively), while fear of infection or worsening of health was not. Path analysis showed that work-related stress associated with the viral epidemic rather than anxiety about the viral epidemic mainly contributed to depression. Conclusion The present observational study indicates that mental health problems of HCWs exposed to COVID-19 are associated with distress in work and social relationship. Early intervention programs focusing on these factors are necessary.

Background: Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a condition characterized by the overlapping clinical features of asthma and COPD. To evaluate the appropriateness of different sets of ACO definition, we compared the clinical characteristics of the previously defined diagnostic criteria and the specialist opinion in this study. Methods: Patients enrolled in the KOrea COpd Subgroup Study (KOCOSS) were evaluated. Based on the questionnaire data, the patients were categorized into the ACO and non-ACO COPD groups according to the four sets of the diagnostic criteria. Results: In total 1,475 patients evaluated: 202 of 1,475 (13.6%), 32 of 1,475 (2.2%), 178 of 1,113 (16.0%), and 305 of 1,250 (24.4%) were categorized as ACO according to the modified Spanish Society of Pneumonology and Thoracic Surgery (SEPAR), American Thoracic Society (ATS) Roundtable, Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and the specialists diagnosis, respectively. The ACO group defined according to the GINA/GOLD criteria showed significantly higher St. George's Respiratory Questionnaire and COPD Assessment Test scores than the non-ACO COPD group. When the modified SEPAR definition was applied, the ACO group showed a significantly larger decrease in the forced expiratory volume in 1 second (FEV1, %). The ACO group defined by the ATS Roundtable showed significantly larger decrease in the forced vital capacity values compared to the non-ACO COPD group (–18.9% vs. –2.2%, p=0.007 and –412 mL vs. –17 mL, p=0.036). The ACO group diagnosed by the specialists showed a significantly larger decrease in the FEV1 (%) compared to the non-ACO group (–5.4% vs. –0.2%, p=0.003). Conclusion In this study, the prevalence and clinical characteristics of ACO varied depending on the diagnostic criteria applied. With the criteria which are relatively easy to use, defining ACO by the specialists diagnosis may be more practical in clinical applications.

Background: Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a condition characterized by the overlapping clinical features of asthma and COPD. To evaluate the appropriateness of different sets of ACO definition, we compared the clinical characteristics of the previously defined diagnostic criteria and the specialist opinion in this study. Methods: Patients enrolled in the KOrea COpd Subgroup Study (KOCOSS) were evaluated. Based on the questionnaire data, the patients were categorized into the ACO and non-ACO COPD groups according to the four sets of the diagnostic criteria. Results: In total 1,475 patients evaluated: 202 of 1,475 (13.6%), 32 of 1,475 (2.2%), 178 of 1,113 (16.0%), and 305 of 1,250 (24.4%) were categorized as ACO according to the modified Spanish Society of Pneumonology and Thoracic Surgery (SEPAR), American Thoracic Society (ATS) Roundtable, Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and the specialists diagnosis, respectively. The ACO group defined according to the GINA/GOLD criteria showed significantly higher St. George's Respiratory Questionnaire and COPD Assessment Test scores than the non-ACO COPD group. When the modified SEPAR definition was applied, the ACO group showed a significantly larger decrease in the forced expiratory volume in 1 second (FEV1, %). The ACO group defined by the ATS Roundtable showed significantly larger decrease in the forced vital capacity values compared to the non-ACO COPD group (–18.9% vs. –2.2%, p=0.007 and –412 mL vs. –17 mL, p=0.036). The ACO group diagnosed by the specialists showed a significantly larger decrease in the FEV1 (%) compared to the non-ACO group (–5.4% vs. –0.2%, p=0.003). Conclusion In this study, the prevalence and clinical characteristics of ACO varied depending on the diagnostic criteria applied. With the criteria which are relatively easy to use, defining ACO by the specialists diagnosis may be more practical in clinical applications.