1.Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea
Eui-Soon KIM ; Sun-Kyeong PARK ; Jong-Chan YOUN ; Hye Sun LEE ; Hae-Young LEE ; Hyun-Jai CHO ; Jin-Oh CHOI ; Eun-Seok JEON ; Sang Eun LEE ; Min-Seok KIM ; Jae-Joong KIM ; Kyung-Kuk HWANG ; Myeong-Chan CHO ; Shung Chull CHAE ; Seok-Min KANG ; Jin Joo PARK ; Dong-Ju CHOI ; Byung-Su YOO ; Jae Yeong CHO ; Kye Hun KIM ; Byung-Hee OH ; Barry GREENBERG ; Sang Hong BAEK
Journal of Korean Medical Science 2024;39(1):e8-
Background:
The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry.
Methods:
A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY).
Results:
Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY).
Conclusion
There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications.
2.Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry
Do Yeon KIM ; Tai Hwan PARK ; Yong-Jin CHO ; Jong-Moo PARK ; Kyungbok LEE ; Minwoo LEE ; Juneyoung LEE ; Sang Yoon BAE ; Da Young HONG ; Hannah JUNG ; Eunvin KO ; Hyung Seok GUK ; Beom Joon KIM ; Jun Yup KIM ; Jihoon KANG ; Moon-Ku HAN ; Sang-Soon PARK ; Keun-Sik HONG ; Hong-Kyun PARK ; Jeong-Yoon LEE ; Byung-Chul LEE ; Kyung-Ho YU ; Mi Sun OH ; Dong-Eog KIM ; Dong-Seok GWAK ; Soo Joo LEE ; Jae Guk KIM ; Jun LEE ; Doo Hyuk KWON ; Jae-Kwan CHA ; Dae-Hyun KIM ; Joon-Tae KIM ; Kang-Ho CHOI ; Hyunsoo KIM ; Jay Chol CHOI ; Joong-Goo KIM ; Chul-Hoo KANG ; Sung-il SOHN ; Jeong-Ho HONG ; Hyungjong PARK ; Sang-Hwa LEE ; Chulho KIM ; Dong-Ick SHIN ; Kyu Sun YUM ; Kyusik KANG ; Kwang-Yeol PARK ; Hae-Bong JEONG ; Chan-Young PARK ; Keon-Joo LEE ; Jee Hyun KWON ; Wook-Joo KIM ; Ji Sung LEE ; Hee-Joon BAE ;
Journal of Korean Medical Science 2024;39(34):e278-
This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.
3.Cohort profile: Multicenter Networks for Ideal Outcomes of Rare Pediatric Endocrine and Metabolic Diseases in Korea (OUTSPREAD study)
Yun Jeong LEE ; Chong Kun CHEON ; Junghwan SUH ; Jung-Eun MOON ; Moon Bae AHN ; Seong Hwan CHANG ; Jieun LEE ; Jin Ho CHOI ; Minsun KIM ; Han Hyuk LIM ; Jaehyun KIM ; Shin-Hye KIM ; Hae Sang LEE ; Yena LEE ; Eungu KANG ; Se Young KIM ; Yong Hee HONG ; Seung YANG ; Heon-Seok HAN ; Sochung CHUNG ; Won Kyoung CHO ; Eun Young KIM ; Jin Kyung KIM ; Kye Shik SHIM ; Eun-Gyong YOO ; Hae Soon KIM ; Aram YANG ; Sejin KIM ; Hyo-Kyoung NAM ; Sung Yoon CHO ; Young Ah LEE
Annals of Pediatric Endocrinology & Metabolism 2024;29(6):349-355
Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.
4.The efficacy of hyperbaric oxygen therapy for skin perfusion following peripheral tissue injury due to usage of inotropes and vasopressors: a case report
Nien Hsiu SUEN ; Chang Hae PYO ; Hyun Kyung PARK ; Keun Hong PARK ; Dongsun CHOI
Clinical and Experimental Emergency Medicine 2024;11(4):387-391
Hyperbaric oxygen therapy (HBOT) has garnered significant attention as a therapeutic modality with potential benefits across a variety of medical conditions, ranging from wound healing and ischemic conditions to neurologic disorders and radiation-induced tissue damage. HBOT involves the administration of 100% oxygen at higher-than-atmospheric pressures, which increases the amount of oxygen dissolved in body fluids and tissues. Those elevated oxygen levels are proposed to facilitate tissue repair, reduce inflammation, and promote angiogenesis. This case report presents a compelling instance of the usefulness of HBOT in promoting skin perfusion and healing following peripheral tissue injury caused by administration of inotropic and vasopressor agents to a septic shock patient.
5.Clinical Efficacy of a Position-Responding Mandibular Advancement Device in Patients With Obstructive Sleep Apnea
Sung-Woon ON ; Dong-Kyu KIM ; Min Hyuk LEE ; Ji Hae LEE ; Kyung Chul LEE ; Soo-Hwan BYUN ; Seok Jin HONG
Clinical and Experimental Otorhinolaryngology 2024;17(4):302-309
Objectives:
. Although mandibular advancement device (MAD) treatment is effective for obstructive sleep apnea (OSA), some concerns remain regarding its potential therapeutic impact and side effects. Thus, we developed a novel MAD that auto-titrates depending on its position in patients with OSA. We conducted a clinical trial to determine the efficacy of an auto-titrating mandibular advancement device (AMAD) for treating OSA.
Methods:
. Fourteen patients diagnosed with OSA participated in this study. Polysomnography (PSG) was performed at the beginning of the clinical trial, and after 3 months of treatment, PSG with AMAD in situ was conducted.
Results:
. The mean scores for the Epworth Sleepiness Scale (ESS) and STOP-Bang were 8.21±4.21 and 5.00±1.00, respectively. After 3 months of AMAD treatment, the STOP-Bang scores improved to 3.75±1.06; however, the ESS scores did not show a significant change. Additionally, we observed statistically significant improvements in several respiratory parameters in the PSG data following AMAD treatment. These included reductions in the apnea-hypopnea index (AHI) (from 32.85±21.71 to 12.93±10.70), supine AHI (from 45.91±23.58 to 15.59±12.76), and lateral AHI (from 13.94±10.95 to 5.49±7.40). Improvements were also noted in the lowest O2 saturation (from 79.71±6.22 to 84.00± 5.71), total arousal number (from 191.14±112.07 to 86.57±48.80), and arousal index (from 33.76±21.00 to 15.05± 8.42). However, there were no significant changes in total sleep time, sleep efficiency, or mean oxygen saturation. Additionally, no major side effects were observed during treatment, specifically related to tooth or jaw pain.
Conclusion
. Our clinical trial found that AMAD improved PSG parameters and reduced the incidence of common side effects. Therefore, AMAD may be an effective alternative treatment for OSA.
6.The efficacy of hyperbaric oxygen therapy for skin perfusion following peripheral tissue injury due to usage of inotropes and vasopressors: a case report
Nien Hsiu SUEN ; Chang Hae PYO ; Hyun Kyung PARK ; Keun Hong PARK ; Dongsun CHOI
Clinical and Experimental Emergency Medicine 2024;11(4):387-391
Hyperbaric oxygen therapy (HBOT) has garnered significant attention as a therapeutic modality with potential benefits across a variety of medical conditions, ranging from wound healing and ischemic conditions to neurologic disorders and radiation-induced tissue damage. HBOT involves the administration of 100% oxygen at higher-than-atmospheric pressures, which increases the amount of oxygen dissolved in body fluids and tissues. Those elevated oxygen levels are proposed to facilitate tissue repair, reduce inflammation, and promote angiogenesis. This case report presents a compelling instance of the usefulness of HBOT in promoting skin perfusion and healing following peripheral tissue injury caused by administration of inotropic and vasopressor agents to a septic shock patient.
7.Clinical Efficacy of a Position-Responding Mandibular Advancement Device in Patients With Obstructive Sleep Apnea
Sung-Woon ON ; Dong-Kyu KIM ; Min Hyuk LEE ; Ji Hae LEE ; Kyung Chul LEE ; Soo-Hwan BYUN ; Seok Jin HONG
Clinical and Experimental Otorhinolaryngology 2024;17(4):302-309
Objectives:
. Although mandibular advancement device (MAD) treatment is effective for obstructive sleep apnea (OSA), some concerns remain regarding its potential therapeutic impact and side effects. Thus, we developed a novel MAD that auto-titrates depending on its position in patients with OSA. We conducted a clinical trial to determine the efficacy of an auto-titrating mandibular advancement device (AMAD) for treating OSA.
Methods:
. Fourteen patients diagnosed with OSA participated in this study. Polysomnography (PSG) was performed at the beginning of the clinical trial, and after 3 months of treatment, PSG with AMAD in situ was conducted.
Results:
. The mean scores for the Epworth Sleepiness Scale (ESS) and STOP-Bang were 8.21±4.21 and 5.00±1.00, respectively. After 3 months of AMAD treatment, the STOP-Bang scores improved to 3.75±1.06; however, the ESS scores did not show a significant change. Additionally, we observed statistically significant improvements in several respiratory parameters in the PSG data following AMAD treatment. These included reductions in the apnea-hypopnea index (AHI) (from 32.85±21.71 to 12.93±10.70), supine AHI (from 45.91±23.58 to 15.59±12.76), and lateral AHI (from 13.94±10.95 to 5.49±7.40). Improvements were also noted in the lowest O2 saturation (from 79.71±6.22 to 84.00± 5.71), total arousal number (from 191.14±112.07 to 86.57±48.80), and arousal index (from 33.76±21.00 to 15.05± 8.42). However, there were no significant changes in total sleep time, sleep efficiency, or mean oxygen saturation. Additionally, no major side effects were observed during treatment, specifically related to tooth or jaw pain.
Conclusion
. Our clinical trial found that AMAD improved PSG parameters and reduced the incidence of common side effects. Therefore, AMAD may be an effective alternative treatment for OSA.
8.Cohort profile: Multicenter Networks for Ideal Outcomes of Rare Pediatric Endocrine and Metabolic Diseases in Korea (OUTSPREAD study)
Yun Jeong LEE ; Chong Kun CHEON ; Junghwan SUH ; Jung-Eun MOON ; Moon Bae AHN ; Seong Hwan CHANG ; Jieun LEE ; Jin Ho CHOI ; Minsun KIM ; Han Hyuk LIM ; Jaehyun KIM ; Shin-Hye KIM ; Hae Sang LEE ; Yena LEE ; Eungu KANG ; Se Young KIM ; Yong Hee HONG ; Seung YANG ; Heon-Seok HAN ; Sochung CHUNG ; Won Kyoung CHO ; Eun Young KIM ; Jin Kyung KIM ; Kye Shik SHIM ; Eun-Gyong YOO ; Hae Soon KIM ; Aram YANG ; Sejin KIM ; Hyo-Kyoung NAM ; Sung Yoon CHO ; Young Ah LEE
Annals of Pediatric Endocrinology & Metabolism 2024;29(6):349-355
Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.
9.Non-Invasive Radiofrequency Hyperthermia Attenuates HMGB1/TLR4/NF-κB Inflammatory Axis in a Chronic Prostatitis/Chronic Pelvic Pain Syndrome Rat Model
Soomin KIM ; Jun Jie PIAO ; Seokhwan BANG ; Hyong Woo MOON ; Hyuk Jin CHO ; U-Syn HA ; Sung-Hoo HONG ; Ji Youl LEE ; Hae Hoon KIM ; Ha Nul KIM ; Kyung-Hwa JEON ; Mahadevan Raj RAJASEKARAN ; Sae Woong KIM ; Woong Jin BAE
The World Journal of Men's Health 2024;42(4):855-864
Purpose:
The primary goal of this study is to evaluate the effect of the non-invasive radiofrequency hyperthermia (RFHT) device on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) rat model and investigate the underlying mechanism.
Materials and Methods:
In this study, Sprague-Dawley rats were randomly distributed into three groups: (1) normal control group, (2) CP/CPPS group, and (3) RFHT group. CP/CPPS rat models were induced by 17β-estradiol and dihydrotestosterone for 4 weeks and RFHT was administered for 5 weeks after model establishment. During RFHT administration, core body temperatures were continuously monitored with a rectal probe. After administering RFHT, we assessed pain index for all groups and collected prostate tissues for Western blot analysis, immunofluorescence, and immunohistochemistry. We also collected adjacent organs to the prostate including urinary bladder, testes, and rectum for safety assessment via H&E staining along with a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay.
Results:
After administering RFHT, pain in rats was significantly alleviated compared to the CP/CPPS group. RFHT reduced high-mobility group box 1 (HMGB1) expression and improved inflammation by downregulating subsequent proinflammatory cytokines through inhibition of the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. In prostate-adjacent organs, no significant histological alteration or inflammatory infiltration was detected. The area of cell death also did not increase significantly after RFHT.
Conclusions
In conclusion, RFHT demonstrated anti-inflammatory effects by inhibiting the HMGB1-TLR4-NF-κB pathway in CP/CPPS rat models. This suggests that RFHT could serve as a safe and promising therapeutic strategy for CP/CPPS.
10.Non-Invasive Radiofrequency Hyperthermia Attenuates HMGB1/TLR4/NF-κB Inflammatory Axis in a Chronic Prostatitis/Chronic Pelvic Pain Syndrome Rat Model
Soomin KIM ; Jun Jie PIAO ; Seokhwan BANG ; Hyong Woo MOON ; Hyuk Jin CHO ; U-Syn HA ; Sung-Hoo HONG ; Ji Youl LEE ; Hae Hoon KIM ; Ha Nul KIM ; Kyung-Hwa JEON ; Mahadevan Raj RAJASEKARAN ; Sae Woong KIM ; Woong Jin BAE
The World Journal of Men's Health 2024;42(4):855-864
Purpose:
The primary goal of this study is to evaluate the effect of the non-invasive radiofrequency hyperthermia (RFHT) device on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) rat model and investigate the underlying mechanism.
Materials and Methods:
In this study, Sprague-Dawley rats were randomly distributed into three groups: (1) normal control group, (2) CP/CPPS group, and (3) RFHT group. CP/CPPS rat models were induced by 17β-estradiol and dihydrotestosterone for 4 weeks and RFHT was administered for 5 weeks after model establishment. During RFHT administration, core body temperatures were continuously monitored with a rectal probe. After administering RFHT, we assessed pain index for all groups and collected prostate tissues for Western blot analysis, immunofluorescence, and immunohistochemistry. We also collected adjacent organs to the prostate including urinary bladder, testes, and rectum for safety assessment via H&E staining along with a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay.
Results:
After administering RFHT, pain in rats was significantly alleviated compared to the CP/CPPS group. RFHT reduced high-mobility group box 1 (HMGB1) expression and improved inflammation by downregulating subsequent proinflammatory cytokines through inhibition of the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. In prostate-adjacent organs, no significant histological alteration or inflammatory infiltration was detected. The area of cell death also did not increase significantly after RFHT.
Conclusions
In conclusion, RFHT demonstrated anti-inflammatory effects by inhibiting the HMGB1-TLR4-NF-κB pathway in CP/CPPS rat models. This suggests that RFHT could serve as a safe and promising therapeutic strategy for CP/CPPS.

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