Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

OBJECTIVES: As few mpox cases have been reported in Korea, we aimed to identify the characteristics of mpox infection by describing our epidemiologic investigation of a woman patient (index patient, the third case in Korea) and a physician who was infected by a needlestick injury (the fourth case). METHODS: We conducted contact tracing and exposure risk evaluation through interviews with these 2 patients and their physicians and contacts, as well as field investigations at each facility visited by the patients during their symptomatic periods. We then classified contacts into 3 levels according to their exposure risk and managed them to minimize further transmission by recommending quarantine and vaccination for post-exposure prophylaxis and monitoring their symptoms. RESULTS: The index patient had sexual contact with a man foreigner during a trip to Dubai, which was considered the probable route of transmission. In total, 27 healthcare-associated contacts across 7 healthcare facilities and 9 community contacts were identified. These contacts were classified into high (7 contacts), medium (9 contacts), and low (20 contacts) exposure risk groups. One high-risk contact was identified as a secondary patient: a physician who was injured while collecting specimens from the index patient. CONCLUSIONS The index patient visited several medical facilities due to progressive symptoms prior to isolation. Although the 2022 mpox epidemic mainly affected young men, especially men who have sex with men, physicians should also consider mpox transmission in the general population for the timely detection of mpox-infected patients.

Background: Anxiety and communication difficulties in the emergency department (ED) may increase for various reasons, including isolation due to coronavirus disease 2019 (COVID-19). However, little research on anxiety and communication in EDs exists. This study explored the isolation-related anxiety and communication experiences of ED patients during the COVID-19 pandemic. Methods: A prospective mixed-methods study was conducted from May to August 2021 at the Samsung Medical Center ED, Seoul. There were two patient groups: isolation and control.Patients measured their anxiety using the State-Trait Anxiety Inventory (STAI X1) at two time points, and we surveyed patients at two time points about factors contributing to their anxiety and communication experiences. These were measured through a mobile web-based survey. Researchers interviewed patients after their discharge. Results: ED patients were not anxious regardless of isolation, and there was no statistical significance between each group at the two time points. STAI X1 was 48.4 (standard deviation [SD], 8.0) and 47.3 (SD, 10.9) for early follow-up and 46.3 (SD, 13.0) and 46.2 (SD, 13.6) for late follow-up for the isolation and control groups, respectively. The clinical process was the greatest factor contributing to anxiety as opposed to the physical environment or communication. Communication was satisfactory in 71.4% of the isolation group and 66.7% of the control group. The most important aspects of communication were information about the clinical process and patient status. Conclusion ED patients were not anxious and were generally satisfied with medical providers’ communication regardless of their isolation status. However, patients need clinical process information for anxiety reduction and better communication.

Background and Objectives: Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation. Methods: and Results: Non-apoptotic concentrations of DEP (10 μg/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including cFos. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 μg/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS. Conclusions Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.

Background: This study reports trends in pediatric out-of-hospital cardiac arrest (OHCA) and factors affecting clinical outcomes by age group. Methods: We identified 4,561 OHCA patients younger than 18 years between January 2009 and December 2018 in the Korean OHCA Registry. The patients were divided into four groups: group 1 (1 year or younger), group 2 (1 to 5 years), group 3 (6 to 12 years), and group 4 (13 to 17 years). The primary outcome was survival to hospital discharge, and the secondary outcomes were return of spontaneous circulation (ROSC) at the emergency department (ED) and good neurological status at discharge. Multivariate logistic analyses were performed. Results: The incidence rate of pediatric OHCA in group 1 increased from 45.57 to 60.89 per 100,000 person-years, while that of the overall population decreased over the 10 years. The rates of ROSC at the ED, survival to hospital discharge, and good neurologic outcome were highest in group 4 (37.9%, 9.7%, 4.9%, respectively) and lowest in group 1 (28.3%, 7.1%, 3.2%). The positive factors for survival to discharge were event location of a public/commercial building or place of recreation, type of first responder, prehospital delivery of automated external defibrillator shock, initial shockable rhythm at the ED. The factors affecting survival outcomes differed by age group. Conclusion This study reports comprehensive trends in pediatric OHCA in the Republic of Korea. Our findings imply that preventive methods for the targeted population should be customized by age group.

Objective: Coronavirus disease 2019 (COVID-19) has notably altered the emergency department isolation protocol, imposing stricter requirements on probable infectious disease patients that enter the department. This has caused adverse effects, such as an increased rate of leave without being seen (LWBS). This study describes the effect of fever/respiratory symptoms as the main cause of isolation regarding LWBS after the COVID-19 pandemic. Methods: We retrospectively analyzed emergency department visits before (March to July 2019) and after (March to July 2020) the COVID-19 pandemic. Patients were grouped based on existing fever or respiratory symptoms, with the LWBS rate as the primary outcome. Logistic regression analysis was used to identify the risk factors of LWBS. Logistic regression was performed using interaction terminology (fever/respiratory symptom patient [FRP] × post–COVID-19) to determine the interaction between patients with FRPs and the COVID-19 pandemic period. Results: A total of 60,290 patients were included (34,492 in the pre–COVID-19, and 25,298 in the post–COVID-19 group). The proportion of FRPs decreased significantly after the pandemic (P < 0.001), while the LWBS rate in FRPs significantly increased from 2.8% to 19.2% (P < 0.001). Both FRPs (odds ratio, 1.76; 95% confidence interval, 1.59–1.84 (P < 0.001) and the COVID-19 period (odds ratio, 2.29; 95% confidence interval, 2.15–2.44; P < 0.001) were significantly associated with increased LWBS. Additionally, there was a significant interaction between the incidence of LWBS in FRPs and the COVID-19 pandemic period (P < 0.001). Conclusion The LWBS rate has increased in FRPs after the COVID-19 pandemic; additionally, the effect observed was disproportionate compared with that of nonfever/respiratory symptom patients.

BACKGROUND: The impact of institutional case volume to graft failure rate after adult kidney transplantation is relatively unclear compared to other solid organ transplantations. METHODS: A retrospective cohort study of 13,872 adult kidney transplantations in Korea was performed. Institutions were divided into low- (< 24 cases/year), medium- (24–60 cases/year), and high- (> 60 cases/year) volume centers depending on the annual case volume. One-year graft failure rate was defined as the proportion of patients who required dialysis or re-transplantation at one year after transplantation. Postoperative in-hospital mortality and long-term graft survival were also measured. RESULTS: After adjustment, one year graft failure was higher in low-volume centers significantly (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.26–1.78; P < 0.001) and medium-volume centers (aOR, 1.87; 95% CI, 1.57–2.23; P < 0.001) compared to high-volume centers. Low-volume centers had significantly higher mortality (aOR, 1.75; 95% CI, 1.15–2.66; P = 0.01) than that of high-volume centers after adjustment. Long-term graft survival of up to 9 years was superior in high-volume centers compared to low- and medium-volume centers (P < 0.001). CONCLUSION: Higher-case volume centers were associated with lower one-year graft failure rate, lower in-hospital mortality, and higher long-term graft survival after kidney transplantation.
Adult ; Cohort Studies ; Dialysis ; Graft Survival ; Hospital Mortality ; Humans ; Kidney Transplantation ; Kidney ; Korea ; Mortality ; Odds Ratio ; Organ Transplantation ; Retrospective Studies ; Transplants

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.
Animals* ; Antidepressive Agents ; Behavior Rating Scale ; Blotting, Western ; Brain-Derived Neurotrophic Factor* ; Cyclic AMP Response Element-Binding Protein ; Depression ; Down-Regulation ; Fibromyalgia* ; Hippocampus ; Immunohistochemistry ; Memory ; Mice ; Models, Animal* ; Pain Measurement ; Pain Threshold ; Prefrontal Cortex ; Risk Factors ; Sensation ; Stress, Psychological