1.Clinical, Mutational, and Transcriptomic Characteristics in Elderly Korean Individuals With Clonal Hematopoiesis Driver Mutations
Inki MOON ; Min Gyu KONG ; Young Sok JI ; Se Hyung KIM ; Seong Kyu PARK ; Jon SUH ; Mi-Ae JANG
Annals of Laboratory Medicine 2023;43(2):145-152
Background:
Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of blood cells originating from somatically mutated hematopoietic stem cells, is common among the elderly and is associated with an increased risk of hematologic malignancies. We investigated the clinical, mutational, and transcriptomic characteristics in elderly Korean individuals with CHIP mutations.
Methods:
We investigated CHIP in 90 elderly individuals aged ≥60 years with normal complete blood counts at a tertiary-care hospital in Korea between June 2021 and February 2022. Clinical and laboratory data were prospectively obtained. Targeted next-generation sequencing of 49 myeloid malignancy driver genes and massively parallel RNA sequencing were performed to explore the molecular spectrum and transcriptomic characteristics of CHIP mutations.
Results:
We detected 51 mutations in 10 genes in 37 (41%) of the study individuals. CHIP prevalence increased with age. CHIP mutations were observed with high prevalence in DNMT3A (26 individuals) and TET2 (eight individuals) and were also found in various other genes, including KDM6A, SMC3, TP53, BRAF, PPM1D, SRSF2, STAG1, and ZRSR2. Baseline characteristics, including age, confounding diseases, and blood cell parameters, showed no significant differences. Using mRNA sequencing, we characterized the altered gene expression profile, implicating neutrophil degranulation and innate immune system dysregulation.
Conclusions
Somatic CHIP driver mutations are common among the elderly in Korea and are detected in various genes, including DNMT3A and TET2. Our study highlights that chronic dysregulation of innate immune signaling is associated with the pathogenesis of various diseases, including hematologic malignancies.
2.Is Treosulfan-Based Conditioning Attractive as a Reduced-Intensity Conditioning Regimen in Korea?
Se Hyung KIM ; Young Sok JI ; Jina YUN ; Seong Hyeok CHOI ; Sung Hee LIM ; Chan Kyu KIM ; Seong Kyu PARK
Journal of Korean Medical Science 2023;38(36):e281-
Background:
Allogeneic hematopoietic stem cell transplantation (HSCT) was not actively performed in elderly acute myeloid leukemia (AML) or myelodysplastic syndrome patients who are at a high-risk based on hematopoietic cell transplantation-specific comorbidity index (HCT-CI). The advent of reduced-intensity conditioning (RIC) regimens has made HSCT applicable in this population. However, the selection of appropriate conditioning is a major concern for the attending physician. The benefits of combination of treosulfan and fludarabine (Treo/Flu) have been confirmed through many clinical studies. Korean data on treosulfan-based conditioning regimen are scarce.
Methods:
A retrospective study was conducted to compare the clinical outcomes of allogeneic HSCT using RIC between 13 patients receiving Treo/Flu and 39 receiving busulfan/ fludarabine (Bu/Flu).
Results:
In terms of conditioning-related complications, the frequency of ≥ grade 2 nausea or vomiting was significantly lower and the duration of symptoms was shorter in the Treo/ Flu group than in the Bu/Flu group. The incidence of ≥ grade 2 mucositis tended to be lower in the Treo/Flu group. In the analysis of transplant outcomes, all events of acute graft versus host disease (GVHD) and ≥ grade 2 acute GVHD occurred more frequently in the Treo/ Flu group. The frequency of Epstein-Barr virus reactivation was significantly higher in the Treo/Flu group (53.8% vs. 23.1%, P = 0.037). Non-relapse mortality (NRM) at 12 months was higher in the Treo/Flu group (30.8% vs. 7.7%, P = 0.035). Significant prognostic factors included disease type, especially secondary AML, disease status and high-risk based on HCT-CI, ≥ grade 2 acute GVHD, and cases requiring ≥ 2 immunosuppressive drugs for treating acute GVHD. In the comparison of survival outcomes according to conditioning regimen, the Bu/Flu group seemed to show better results than the Treo/Flu group (60% vs.46.2%, P = 0.092 for overall survival; 56.4% vs. 38.5%, P = 0.193 for relapse-free survival). In additional analysis for only HCT-CI high-risk groups, there was no difference in transplant outcomes except that the Treo/Flu group tended to have a higher NRM within one year after transplantation. Survival outcomes of both groups were similar.
Conclusion
This study suggests that Treo/Flu conditioning may be an alternative to Bu/Flu regimen in elderly patients with high-risk who are not suitable for standard conditioning.
3.The Efficacy and Safety of a Human Perirenal Adipose TissueDerived Stromal Vascular Fraction in an Interstitial Cystitis Rat Model
Ji Yong HA ; Eun Hye LEE ; So Young CHUN ; Jun Nyung LEE ; Yun-Sok HA ; Jae-Wook CHUNG ; Bo Hyun YOON ; Minji JEON ; Hyun Tae KIM ; Tae Gyun KWON ; Eun Sang YOO ; Bum Soo KIM
Tissue Engineering and Regenerative Medicine 2023;20(2):225-237
BACKGROUND:
Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients’ quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model.
METHODS:
From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 lg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation.
RESULTS:
The mean pain scores in the SVF 20 ll group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group.In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group.
CONCLUSION
This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.
4.Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers
Sung Hee LIM ; Han Jo KIM ; Se Hyung KIM ; Seong Hyeok CHOI ; Bora KIM ; Ji Youn KIM ; Young Sok JI ; Tark KIM ; Eun Ju CHOO ; Jung Chan JUNG ; Ji Eun MOON ; Chan Kyu KIM ; Seong Kyu PARK ; Jina YUN
Journal of Korean Medical Science 2023;38(13):e103-
Background:
Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine.
Methods:
Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines.
Results:
A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study.Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicroninfected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed.
Conclusion
Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination.Further studies are needed to understand the characteristics of immunogenicity in these populations.
5.Clinical Experience of Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients Aged 60 Years and Older in South Korea
Young Sok JI ; Jae-Sook AHN ; Jina YUN ; Geum Ha JANG ; Sung Hee LIM ; Se Hyung KIM ; Chan Kyu KIM ; Jong Ho WON ; Seong Kyu PARK
Yonsei Medical Journal 2023;64(2):123-132
Purpose:
The purpose of this study is to share our outcomes and experiences on allogeneic hematopoietic stem cell transplantation (HSCT) in elderly patients aged 60 years and older with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in South Korea, and to compare them with other studies.
Materials and Methods:
We analyzed the clinical outcomes of 116 patients with AML or MDS aged 60 years and older who underwent allogeneic HSCT. We also analyzed which pretreatment factors affect the overall survival (OS) after allogeneic HSCT.
Results:
Neutrophil and platelet engraftment were achieved at median day +11 [interquartile range (IQR) 10–15] and +14 (IQR 11–19), respectively. A complete donor chimerism was confirmed in 65 (56.0%) patients at 3 weeks and in 63 (54.3%) patients at 3 months after HSCT. The estimated incidence of grade II–IV acute graft-versus-host disease (GVHD) at day 100 was 13.7%. The estimated incidence of chronic GVHD at 2 years was 38.8%. Within a median follow-up of 14 months after HSCT, OS was 64% at 1 year and 55% at 2 years, and non-relapse mortality (NRM) was 20% at 1 year and 28% at 2 years. Multivariate analysis revealed that male sex and Hematopoietic Cell Transplantation-Specific Comorbidity Index ≥3 were associated with poor OS.
Conclusion
This study showed that allogeneic HSCT in elderly adults aged 60 and older can be performed with successful engraftment and acceptable NRM and OS are expected given the generally known survival of patients with higher risk MDS and poor risk AML.
7.Accuracy of Intraocular Pressure Measurements of Eyes with Therapeutic Contact Lenses after Vitrectomy
Ja Young MOON ; Yung Hui KIM ; Yong-Sok JI
Journal of the Korean Ophthalmological Society 2022;63(5):426-433
Purpose:
To evaluate the accuracy of intraocular pressure (IOP) measurements obtained by a rebound and non-contact tonometer in eyes with a therapeutic contact lens (CL) after vitrectomy.
Methods:
In 60 eyes of 60 patients who underwent vitrectomy for vitreoretinal disease, IOP was measured using a rebound tonometer (iCare ic200®; IOPRT) and non-contact computerized air puff tonometer (CT-80, IOPNCT), before and after wearing a CL (Purevision2®, +0.0 diopter). The mean IOP of three consecutive measurements were analyzed, and a comparative analysis with IOP measured by a Goldman applanation tonometer (IOPGAT) was performed.
Results:
The mean IOPRT without and with the CL was 12.55 ± 5.43 and 13.12 ± 5.13 mmHg, respectively, showing a statistically significant difference (p = 0.02) and strong positive correlation (r = 0.90, p < 0.001). The mean IOPNCT with and without the CL was 12.18 ± 3.24 and 12.17 ± 3.14 mmHg, showing no statistically significant difference (p = 0.17). The consistency with IOPGAT (12.57 ± 5.22 mmHg) was highest in IOPRT without the CL, followed by IOPRT with the CL, IOPNCT without the CL, and IOPNCT with the CL (intraclass correlation coefficients = 0.955, 0.945, 0.856, and 0.850, respectively). In addition, the rebound tonometer successfully measured IOP, regardless of whether the CL was worn; however, the non-contact tonometer failed to measure IOP in seven eyes without the CL and nine with the CL. No difference was observed according to intraocular tamponade type.
Conclusions
A rebound tonometer can be used as an alternative IOL measuring method in eyes for which it is difficult to use a Goldman applanation tonometer due to the postoperative presence of a therapeutic CL.
8.The workload of emergency physician using Korean Emergency Physician Survey
Yoo Sang YOON ; DongWoo SON ; Ji Hun KANG ; Kwang Hyun CHO ; In Byung KIM ; Mi Jin LEE ; Hyung Min LEE ; Kyung Hye PARK ; Song Yi PARK ; Hong Jae KIM ; Dong Hoon KEY ; Beom Sok SEO ; Young Min JOO ; Chang Gun JEE ; Suk Jae CHOI ; In Hwan YEO ; Woo Jin JUNG ; Dae Sung LIM ; Eu Sun LEE
Journal of the Korean Society of Emergency Medicine 2022;33(4):49-56
Objective:
It has been reported that emergency physicians experience high levels of depression and psychological burnout due to night shifts and tend to consider early retirement. This study intended to check working hours and intensity, individual health, satisfaction, and overall welfare, given the increase in the numbers of emergency physicians.
Methods:
The study used the results of the ‘2020 Korean Emergency Physician Survey (KEPS)’ conducted from January 15 to February 26, 2021, which targeted 2,138 emergency physicians registered with the Korean Society of Emergency Medicine. The survey was conducted online through the web and mobile application.
Results:
One thousand three hundred seven out of the 2,167 emergency physicians (60.3%) registered at the society responded. The average age of the respondents was 42.6 years, and there were 1,148 male emergency physicians and 158 female emergency physicians. The average professional experience was 8.2 years, with 325 professors, 122 commissioned doctors, 648 public servants of which 90 had military service, and 45 medical practitioners.
Conclusion
In conclusion, the number of working hours of emergency physicians showed a decreasing trend compared to 2010 and 2015. However, emergency physicians often expected early retirement. This suggests that, while the absolute working hours are decreasing, the actual working intensity has not decreased. For the proper development of the emergency medical system, it is necessary to establish a stable working environment for emergency physicians. A systematic study is needed on the working hours and work intensity of emergency physicians.
9.Analysis of work, life, and occupation perception of emergency physician by generations
Jun Se PARK ; Beom Sok SEO ; Kwang Hyun CHO ; In Byung KIM ; Mi Jin LEE ; Yoo Sang YOON ; Kyung Hye PARK ; Song Yi PARK ; Hong Jae KIM ; Dong Hoon KEY ; Hyung Min LEE ; Young Min JOO ; Chang Gun JEE ; Suk Jae CHOI ; In Hwan YEO ; Ji Hun KANG ; Woo Jin JUNG ; Dae Sung LIM ; Eu Sun LEE
Journal of the Korean Society of Emergency Medicine 2022;33(4):38-48
Objective:
As the history of emergency medicine grows longer, emergency medicine specialists are observed to comprise various age groups. There have been no prior studies on the generation shift analysis of emergency medicine specialists. Our study is designed to identify the characteristics of each generation and predict the generation shift in emergency medicine physicians.
Methods:
The analysis was based on the results of the 2020 survey of emergency medicine specialists. The study was conducted on 1,307 respondents and finally, the responses of 967 people were analyzed after excluding 199 who were not in charge of emergency room treatments and 141 who gave incomplete responses. The respondents were divided into four groups based on the following generations: first generation (1996-1999), second generation (2000-2008), third generation (2009-2014), and fourth generation (2015-2020), classified by the year in which they acquired their emergency medicine board license. The intergenerational difference analysis was done using the Kruskall-Wallis test.
Results:
The first generation was characterized by a high proportion of university hospital professors, large non-clinical activity hours, a few night shifts, higher social contributions, low satisfaction with the training and education environment, and a high retirement age compared to the later generations. In the second generation, the characteristics of the first, third, and fourth generations were generally mixed. The third and fourth generations showed similar characteristics overall, though there were differences in some categories.
Conclusion
There were significant differences by generation in the working environments, motivation for application, and retirement age. This is the first study that quantifies generational differences. Considering these trends, a discussion about the work environment needs to be initiated.
10.The prevalence and related factors of depression in emergency physicians of Korea: results from the 2020 Korean Emergency Physician Survey
Dae Sung LIM ; Song Yi PARK ; Hyung Min LEE ; Kwang Hyun CHO ; In Byung KIM ; Mi Jin LEE ; Yoo Sang YOON ; Kyung Hye PARK ; Hong Jae KIM ; Dong Hoon KEY ; Beom Sok SEO ; Young Min JOO ; Chang Gun JEE ; Suk Jae CHOI ; In Hwan YEO ; Ji Hun KANG ; Woo Jin JUNG ; Eu Sun LEE
Journal of the Korean Society of Emergency Medicine 2022;33(4):29-37
Objective:
Emergency physicians are constantly exposed to night shifts and stress due to the nature of their work, resulting in health problems such as substance abuse, depression, and suicidal ideation. To date, depression in Korean emergency physicians has never been investigated. The present study endeavors to identify the prevalence and factors related to depression in emergency physicians in Korea.
Methods:
The present study retrospectively analyzed data from the 2020 Korean Emergency Physician Survey. The prevalence of depression was evaluated using the PHQ-9 (Patient Healthcare Questionnaire-9). Multivariable logistic regression analysis was used to identify the factors related to depression and other variables.
Results:
The overall response rate of the survey was 61.3% (1,307/2,138). A total of 1,102 respondents completed the PHQ- 9 and were analyzed. The prevalence of depression was 27.0% (95% confidence interval [CI], 27.8-33.6). Following factors were found to be associated with depression: military service as the type of position (odds ratio [OR], 0.316; 95% CI, 0.126- 0.794), schedule satisfaction (OR, 0.523; 95% CI, 0.356-0.769), health perspective (OR, 0.408; 95% CI, 0.252-0.662), weekly exercise (OR, 0.879; 95% CI, 0.774-0.998), sleep quality (OR, 4.728; 95% CI, 3.329-6.715), regular diet (OR, 0.380; 95% CI, 0.239-0.605), nighttime snacking (OR, 1.607; 95% CI, 1.124-2.298), and job satisfaction (OR, 0.456; 95% CI, 0.305-0.682).
Conclusion
More than a quarter of respondents had depression. Job satisfaction, schedule satisfaction, and a healthy lifestyle were negatively related to depression. However, poor sleep quality showed a significantly positive association, which suggests the necessity for a long-term follow-up.

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