1.Thyroid Dyshormonogenesis Due to Dual Oxidase Maturation Factor 2 Mutation as Non-Transient Status of Hypothyroidism
Jisu LEE ; Sang-gyeom KIM ; Arum OH ; Heon-Seok HAN
International Journal of Thyroidology 2022;15(1):54-59
Dual oxidase maturation factor 2 (DUOXA2) is necessary for the enzymatic activity of dual oxidase 2 (DUOX2) to generate hydrogen peroxide production during thyroid hormone synthesis. We describe two Korean children, who were initially suspected to have transient congenital hypothyroidism (CH), but later confirmed to have permanent CH caused by DUOXA2 mutation. Treatment with levothyroxine was discontinued after confirming thyroid-stimulating hormone (TSH) level to be below 10 μU/mL and normal thyroid scan at the first or second trial-off therapy. However, after therapy cessation, TSH elevated to more than 10 μU/mL, and goiter developed in case 2. As a result, levothyroxine was resumed. Next-generation sequencing showed compound heterozygous mutations of DUOXA2 at Y138X and Y246X in case 1 and homozygous mutations of DUOXA2 at Y246X in case 2. In this report, a longer follow-up is recommended even after treatment termination in transient CH, and genetic studies might help assess the permanence of hypothyroidism in cases of mildly elevated TSH after trial-off therapy.
2.The Prevalence and Risk Factors of Clostridioides difficile Infection in Inflammatory Bowel Disease: 10-Year South Korean Experience Based on the National Database
Eun Mi SONG ; Arum CHOI ; Sukil KIM ; Sung Hoon JUNG
Journal of Korean Medical Science 2023;38(47):e359-
Background:
Few studies evaluate the epidemiology and risk factors of Clostridioides difficile infection (CDI) in Asian patients with inflammatory bowel disease (IBD). We investigated the year-end prevalence, cumulative incidence and risk factors of CDI in Asian patients with IBD using a large-scale population-based cohort in Korea.
Methods:
Using the National Health Insurance Service database, we identified patients with IBD and sex- and age-matched controls without IBD between 2008 and 2018. The year-end prevalence and cumulative incidence of CDI were compared among patients with Crohn’s disease (CD) and ulcerative colitis (UC) with controls. The risk factors for CDI were evaluated.
Results:
Among the 54,836 patients with IBD and 109,178 controls, CDI occurred in 293 patients with IBD and 87 controls. The annual year-end prevalence of CDI in patients with IBD increased from 8.6/10,000 persons in 2008 to 22.3/10,000 persons in 2018. The risk of CDI was higher in both patients with CD and UC than that in the matched controls (hazard ratio [HR], 7.285; 95% confidence interval [CI], 5.388–9.851; P < 0.001 and HR, 7.487; 95% CI, 5.796–9.670; P < 0.001, respectively). Among patients with IBD, the risk factors for CDI included older age, female sex, high Charlson comorbidity index score, and IBD-related medications including oral 5-aminosalicylic acid, immunomodulatory agents, biologics, and steroids used for > 90 days.
Conclusion
The risk of CDI in Korean patients with IBD was approximately seven times higher than that in controls without IBD, and the annual year-end prevalence of CDI continuously increased from 2008 to 2018.
3.Keratinization of Lung Squamous Cell Carcinoma Is Associated with Poor Clinical Outcome.
Hye Jung PARK ; Yoon Jin CHA ; Seong Han KIM ; Arum KIM ; Eun Young KIM ; Yoon Soo CHANG
Tuberculosis and Respiratory Diseases 2017;80(2):179-186
BACKGROUND: Although the World Health Organization (WHO) classification of lung squamous cell carcinoma (SCC) was revised in 2015, its clinical implications for lung SCC subsets remain unclear. We investigated whether the morphologic characteristics of lung SCC, including keratinization, were associated with clinical parameters and clinical outcome of patients. METHODS: A total of 81 patients who underwent curative surgical resection of diagnosed lung SCC, were enrolled in this study. Attributes such as keratinization, tumor budding, single cell invasion, and nuclear size within the tumor, as well as immunohistochemistry of Bcl-xL and pS6 expressions, were evaluated. RESULTS: The keratinizing and nonkeratinizing subtypes did not differ with respect to age, sex, TNM stage, and morphologic parameters such as nuclear diameter, tumor budding, and single cell invasion at the tumor edge. Most patients with the keratinizing subtype (98.0%) had a history of smoking, whereas the nonkeratinizing group had a relatively higher proportion of never-smokers relative to the keratinizing group (24.0% vs. 2.0%; p=0.008, chi-square test). Expression of pS6 (a surrogate marker of mammalian target of rapamycin complex 1 [mTORC1] signaling that regulates keratinocyte differentiation), and Bcl-xL (a key anti-apoptotic molecule that may inhibit keratinization), did not correlate significantly with the presence of keratinization. Patients with the keratinizing subtype had a significantly shorter overall survival (85.2 months vs. 135.7 months, p=0.010, log-rank test), and a multivariate analysis showed that keratinization was an independent, poor prognostic factor (hazard ratio, 2.389; 95% confidence interval, 1.090–5.233; p=0.030). CONCLUSION: In lung SCC, keratinization is associated with a poor prognosis, and might be associated with smoking.
bcl-X Protein
;
Biomarkers
;
Carcinoma, Squamous Cell*
;
Classification
;
Epithelial Cells*
;
Humans
;
Immunohistochemistry
;
Keratinocytes
;
Lung*
;
Multivariate Analysis
;
Prognosis
;
Sirolimus
;
Smoke
;
Smoking
;
World Health Organization
4.ABT-737, a BH3 Mimetic, Enhances the Therapeutic Effects of Ionizing Radiation in K-ras Mutant Non-Small Cell Lung Cancer Preclinical Model
Jung Mo LEE ; Hey Soo KIM ; Arum KIM ; Yoon Soo CHANG ; Jin Gu LEE ; Jaeho CHO ; Eun Young KIM
Yonsei Medical Journal 2022;63(1):16-25
Purpose:
Tumor radioresistance and dose-limiting toxicity restrict the curative potential of radiotherapy, requiring novel approaches to overcome the limitations and augment the efficacy. Here, we investigated the effects of signal transducer and activator of transcription 3 (STAT3) activation and autophagy induction by irradiation on antiapoptotic proteins and the effectiveness of the BH3 mimetic ABT-737 as a radiosensitizer using K-ras mutant non-small cell lung cancer (NSCLC) cells and a Kras G12D :p53 fl/fl mouse (KP mouse) model.
Materials and Methods:
A549 and H460 cells were irradiated, and the expression of Bcl-2 family proteins, JAK/STAT transcriptional pathway, and autophagic pathway were evaluated by immunoblotting. The radiosensitizing effects of ABT-737 were evaluated using A549 and H460 cell lines with clonogenic assays and also by a KP mouse model with microcomputed tomography and immunohistochemistry.
Results:
In A549 and H460 cells and mouse lung tissue, irradiation-induced overexpression of the antiapoptotic molecules BclxL, Bcl-2, Bcl-w, and Mcl-1 through JAK/STAT transcriptional signaling induced dysfunction of the autophagic pathway. After treatment with ABT-737 and exposure to irradiation, the number of surviving clones in the cotreatment group was significantly lower than that in the group treated with radiation or ABT-737 alone. In the KP mouse lung cancer model, cotreatment with ABT-737 and radiation-induced significant tumor regression; however, body weight changes in the combination group were not significantly different, suggesting that combination treatment did not cause systemic toxicity.
Conclusion
These findings supported the radiosensitizing activity of ABT-737 in preclinical models, and suggested that clinical trials using this strategy may be beneficial in K-ras mutant NSCLC.
5.Pubertal outcomes and sex of rearing of patients with ovotesticular disorder of sex development and mixed gonadal dysgenesis
Yoon Myung KIM ; Arum OH ; Kun Suk KIM ; Han Wook YOO ; Jin Ho CHOI
Annals of Pediatric Endocrinology & Metabolism 2019;24(4):231-236
PURPOSE: Patients with ovotesticular disorder of sex development (DSD) and mixed gonadal dysgenesis (MGD) usually present with asymmetric gonads and have wide phenotypic variations in internal and external genitalia. The differential diagnosis of these conditions is based on karyotype and pathological findings of the gonads. This study investigated the clinical features at presentation, karyotype, sex of rearing, and pubertal outcomes of patients with ovotesticular DSD and MGD.METHODS: The study comprised 23 patients with DSD who presented with asymmetric gonads. The presenting features, karyotype, sex of rearing, and pubertal outcomes were reviewed retrospectively.RESULTS: All 23 patients presented with ambiguous genitalia at a median age of 1 month (range, 1 day–1.6 years). Müllerian duct remnants were identified in 15 of 23 patients (65.2%). Fourteen patients were diagnosed with ovotesticular DSD, whereas the other 9 were diagnosed with MGD. Eight of 14 patients (57.1%) with ovotesticular DSD were raised as males, while 7 of 9 patients with MGD (77.8%) were assigned as males. One male-assigned patient with ovotesticular DSD changed to female sex at age 20 years.CONCLUSION: Patients with ovotesticular DSD and MGD manifest overlapping clinical presentations and hormonal profiles. It is difficult to determine the sex of rearing and predict long-term pubertal outcomes. Therefore, long-term follow-up is required to monitor spontaneous puberty, sex outcome, and urological and gynecological complications.
Adolescent
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Diagnosis, Differential
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Disorders of Sex Development
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Female
;
Follow-Up Studies
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Genitalia
;
Gonadal Dysgenesis
;
Gonadal Dysgenesis, Mixed
;
Gonads
;
Humans
;
Karyotype
;
Male
;
Ovotesticular Disorders of Sex Development
;
Puberty
;
Retrospective Studies
6.Estimation of Supply and Demand for Cardiologists in Korea
Mira KIM ; Kyunghee CHAE ; Ju Mee WANG ; Arum CHOI ; Jang-Whan BAE ; Keon-Woong MOON ; Sukil KIM
Korean Circulation Journal 2024;54(1):1-12
Background and Objectives:
The objective of this study was to estimate the supply and demand for cardiologists in Korea and provide evidence for healthcare policy to ensure a stable and adequate workforce for optimal cardiovascular disease management.
Methods:
Past trends of inflow and outflow of cardiologists were used to make crude projections, which were then adjusted based on demands of services to obtain final projections. Inflow of cardiologists was estimated using second-order polynomial regression and demand for cardiology care was estimated using linear regression.
Results:
There were 1,139 active cardiologists who were under the age of 65 in clinical practice in Korea. The estimated number of cardiologists from 2022 to 2040 showed that the number of cardiologists would peak at 1,344 in 2032 and gradually decrease thereafter. We also estimated an increase of 947,811 cases of heart-related procedures annually from 2023 to 2032. The number of heart-related procedures per cardiologist would increase 1.4 times from 12,964 in 2023 to 17,862 in 2032. The estimated number of emergency patients per cardiologist under 50 years old would almost double from 544 in 2022 to 987 in 2032.
Conclusions
We expect significant shortage of cardiologists in Korea within the next 10 years. The number of emergency patients per cardiologist will increase by nearly 50%, leading to high individual workload for cardiologists. To prevent this imbalance between supply and demand, an organized and collective approach by the specialty of cardiology is imperative to produce a balanced workforce.
7.Estimation of Supply and Demand for Cardiologists in Korea
Mira KIM ; Kyunghee CHAE ; Ju Mee WANG ; Arum CHOI ; Jang-Whan BAE ; Keon-Woong MOON ; Sukil KIM
Korean Circulation Journal 2024;54(1):1-12
Background and Objectives:
The objective of this study was to estimate the supply and demand for cardiologists in Korea and provide evidence for healthcare policy to ensure a stable and adequate workforce for optimal cardiovascular disease management.
Methods:
Past trends of inflow and outflow of cardiologists were used to make crude projections, which were then adjusted based on demands of services to obtain final projections. Inflow of cardiologists was estimated using second-order polynomial regression and demand for cardiology care was estimated using linear regression.
Results:
There were 1,139 active cardiologists who were under the age of 65 in clinical practice in Korea. The estimated number of cardiologists from 2022 to 2040 showed that the number of cardiologists would peak at 1,344 in 2032 and gradually decrease thereafter. We also estimated an increase of 947,811 cases of heart-related procedures annually from 2023 to 2032. The number of heart-related procedures per cardiologist would increase 1.4 times from 12,964 in 2023 to 17,862 in 2032. The estimated number of emergency patients per cardiologist under 50 years old would almost double from 544 in 2022 to 987 in 2032.
Conclusions
We expect significant shortage of cardiologists in Korea within the next 10 years. The number of emergency patients per cardiologist will increase by nearly 50%, leading to high individual workload for cardiologists. To prevent this imbalance between supply and demand, an organized and collective approach by the specialty of cardiology is imperative to produce a balanced workforce.
8.Estimation of Supply and Demand for Cardiologists in Korea
Mira KIM ; Kyunghee CHAE ; Ju Mee WANG ; Arum CHOI ; Jang-Whan BAE ; Keon-Woong MOON ; Sukil KIM
Korean Circulation Journal 2024;54(1):1-12
Background and Objectives:
The objective of this study was to estimate the supply and demand for cardiologists in Korea and provide evidence for healthcare policy to ensure a stable and adequate workforce for optimal cardiovascular disease management.
Methods:
Past trends of inflow and outflow of cardiologists were used to make crude projections, which were then adjusted based on demands of services to obtain final projections. Inflow of cardiologists was estimated using second-order polynomial regression and demand for cardiology care was estimated using linear regression.
Results:
There were 1,139 active cardiologists who were under the age of 65 in clinical practice in Korea. The estimated number of cardiologists from 2022 to 2040 showed that the number of cardiologists would peak at 1,344 in 2032 and gradually decrease thereafter. We also estimated an increase of 947,811 cases of heart-related procedures annually from 2023 to 2032. The number of heart-related procedures per cardiologist would increase 1.4 times from 12,964 in 2023 to 17,862 in 2032. The estimated number of emergency patients per cardiologist under 50 years old would almost double from 544 in 2022 to 987 in 2032.
Conclusions
We expect significant shortage of cardiologists in Korea within the next 10 years. The number of emergency patients per cardiologist will increase by nearly 50%, leading to high individual workload for cardiologists. To prevent this imbalance between supply and demand, an organized and collective approach by the specialty of cardiology is imperative to produce a balanced workforce.
9.Laboratory analysis of acute acetaminophen overdose patients in Emergency Medical Centers: including analysis of one toxicological laboratory data
In Chan KIM ; Sinae WON ; Arum LEE ; Haeun JUNG ; Jeongsun LEE ; Bum Jin OH
Journal of The Korean Society of Clinical Toxicology 2021;19(1):31-37
Purpose:
Acetaminophen (APAP) is a widely available drug responsible for a large part of drug-induced hepatotoxicity in developed countries. Although acetaminophen overdose cases in Korea are being continuously reported, there are no reports related to the level of this drug in the patient’s blood or of laboratory analysis at emergency departments (ED). This study sought to analyze the acetaminophen overdose cases at a toxicological laboratory and to survey APAP analysis services offered at select EDs.
Methods:
We analyzed the demographic and analytic data at a toxicological laboratory run by the National Emergency Medical Center (NMC) in 2019-2020. We surveyed the APAP laboratory service in the 38 regional emergency medical centers (EMCs) and 68 local EMCs near the toxicological laboratory.
Results:
We studied 175 acute poisoning cases (112 women) with positive blood APAP results (mean age 47.0±24.1 years).Suicide attempts comprised 40.0% of the cases and 30.3% APAP overdose events. In the univariate analysis, we observed that patients were significantly younger, with fewer underlying medical diseases. There were a higher number of APAP overdose events, more favorable initial mental status, more toxic quantity intake in the above treatment line group (p<0.05), In multivariate analysis, the toxic amount intake was significantly more frequent in the above treatment line group (p<0.01). Hospital APAP analysis services were available in six EMCs (3/38 regional and 3/68 local). The hospital blood APAP level reporting intervals were shorter than outside-hospital laboratory services (p<0.01, regional 7.0±3.0 vs. 40.6±27.5, local 5.3±3.1 vs. 57.9±45.1 hours).The NMC toxicological laboratory reporting interval was shorter than the other outside-hospital laboratories (p<0.01, regional 5.7± 0.6 vs. 50.2±22.7 local 7.5±3.0 vs. 70.5±41.5 hours).
Conclusion
Over the treatment line group, toxic amount intake was significantly more frequent. Only six of 106 EMCs have their own APAP analysis service in their hospitals.
10.Risk Factors for the Occurrence and Severity of Vertebral Fractures in Inflammatory Bowel Disease Patients: A Nationwide Population-Based Cohort Study
Arum CHOI ; Sung Hoon JUNG ; Sukil KIM ; Jun-Seok LEE
Journal of Korean Medical Science 2023;38(28):e210-
Background:
The risk of vertebral fractures is increased in inflammatory bowel disease (IBD) patients. However, whether the severity of vertebral fractures differs between IBD patients and the general population, or between patients with Crohn’s disease (CD) and ulcerative colitis (UC), is unknown.
Methods:
We investigated risk factors associated with the occurrence and severity of vertebral fractures in IBD patients using The National Healthcare Insurance Service (NHIS) database. We defined the patients who underwent vertebroplasty or kyphoplasty after being diagnosed with a vertebral fracture as having a severe vertebral fracture than those with only diagnosis codes.
Results:
From 2008 to 2018, there were 33,778 patients with IBD (24,370 UC patients and 9,408 CD patients) and 101,265 patients in the reference population. The incidence rate ratio of vertebral fractures in the IBD patients was 1.27 per 1,000 person-years (95% confidence interval [CI], 1.26–1.27). The risk of vertebral fracture was higher in CD and UC patients than in the matched reference group (hazard ratio [HR], 1.59; 95% CI, 1.31–1.92; P < 0.001 and HR, 1.26; 95% CI, 1.14–1.41; P < 0.001, respectively). In a multivariate analysis, the occurrence of vertebral fracture was associated with CD (HR, 1.31; 95% CI, 1.08–1.59; P = 0.006), older age (CD: HR, 1.09; 95% CI, 1.08–1.09; P < 0.001 and UC: HR, 1.09; 95% CI, 1.08–1.09; P < 0.001), female sex (CD: HR, 1.81; 95% CI, 1.63–2.01; P < 0.001 and UC: HR, 2.02; 95% CI, 1.83–2.22; P < 0.001), high Charlson Comorbidity Index (CCI) score (CD: HR, 1.42; 95% CI, 1.23–1.63; P < 0.001 and UC: HR, 1.46; 95% CI, 1.29–1.65, P < 0.001), and long-term steroid use (CD:HR, 3.71; 95% CI, 2.84–3.37; P < 0.001 and UC: HR, 3.88; 95% CI, 3.07–4.91; P < 0.001). The severity of vertebral fractures was associated with IBD (CD: HR, 1.82; 95% CI, 1.17–2.83; P = 0.008 and UC: HR, 1.49; 95% CI, 1.17–1.89; P < 0.001) and older age (HR, 1.06; 95% CI, 1.05–1.07; P < 0.001).
Conclusion
Vertebral fractures occur frequently and more severely in IBD patients, particularly those with CD. Therefore, we suggest monitoring of bone density, regular vitamin D supply, and reducing the use of corticosteroids to prevent vertebral fractures in IBD patients who are older, female, or have comorbidities.