1.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
2.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
3.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
4.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
5.Novel carbazole attenuates vascular remodeling through STAT3/CIAPIN1 signaling in vascular smooth muscle cells.
Joo-Hui HAN ; Jong-Beom HEO ; Hyung-Won LEE ; Min-Ho PARK ; Jangmi CHOI ; Eun Joo YUN ; Seongpyo LEE ; Gyu Yong SONG ; Chang-Seon MYUNG
Acta Pharmaceutica Sinica B 2025;15(3):1463-1479
This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.
6.Association between mechanical power and intensive care unit mortality in Korean patients under pressure-controlled ventilation
Jae Kyeom SIM ; Sang-Min LEE ; Hyung Koo KANG ; Kyung Chan KIM ; Young Sam KIM ; Yun Seong KIM ; Won-Yeon LEE ; Sunghoon PARK ; So Young PARK ; Ju-Hee PARK ; Yun Su SIM ; Kwangha LEE ; Yeon Joo LEE ; Jin Hwa LEE ; Heung Bum LEE ; Chae-Man LIM ; Won-Il CHOI ; Ji Young HONG ; Won Jun SONG ; Gee Young SUH
Acute and Critical Care 2024;39(1):91-99
Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. Methods: We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. Results: A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P<0.001). In logistic regression analysis, only MPPCV was significantly associated with ICU mortality (odds ratio, 1.090; 95% confidence interval, 1.029–1.155; P=0.003). There was no significant effect of the interaction between MPPCV and use of NMBA on ICU mortality (P=0.579). Conclusions: MPPCV is associated with ICU mortality in patients mechanically ventilated with PCV mode, regardless of NMBA use.
7.Association between mechanical power and intensive care unit mortality in Korean patients under pressure-controlled ventilation
Jae Kyeom SIM ; Sang-Min LEE ; Hyung Koo KANG ; Kyung Chan KIM ; Young Sam KIM ; Yun Seong KIM ; Won-Yeon LEE ; Sunghoon PARK ; So Young PARK ; Ju-Hee PARK ; Yun Su SIM ; Kwangha LEE ; Yeon Joo LEE ; Jin Hwa LEE ; Heung Bum LEE ; Chae-Man LIM ; Won-Il CHOI ; Ji Young HONG ; Won Jun SONG ; Gee Young SUH
Acute and Critical Care 2024;39(1):91-99
Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. Methods: We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. Results: A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P<0.001). In logistic regression analysis, only MPPCV was significantly associated with ICU mortality (odds ratio, 1.090; 95% confidence interval, 1.029–1.155; P=0.003). There was no significant effect of the interaction between MPPCV and use of NMBA on ICU mortality (P=0.579). Conclusions: MPPCV is associated with ICU mortality in patients mechanically ventilated with PCV mode, regardless of NMBA use.
8.Association between mechanical power and intensive care unit mortality in Korean patients under pressure-controlled ventilation
Jae Kyeom SIM ; Sang-Min LEE ; Hyung Koo KANG ; Kyung Chan KIM ; Young Sam KIM ; Yun Seong KIM ; Won-Yeon LEE ; Sunghoon PARK ; So Young PARK ; Ju-Hee PARK ; Yun Su SIM ; Kwangha LEE ; Yeon Joo LEE ; Jin Hwa LEE ; Heung Bum LEE ; Chae-Man LIM ; Won-Il CHOI ; Ji Young HONG ; Won Jun SONG ; Gee Young SUH
Acute and Critical Care 2024;39(1):91-99
Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. Methods: We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. Results: A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P<0.001). In logistic regression analysis, only MPPCV was significantly associated with ICU mortality (odds ratio, 1.090; 95% confidence interval, 1.029–1.155; P=0.003). There was no significant effect of the interaction between MPPCV and use of NMBA on ICU mortality (P=0.579). Conclusions: MPPCV is associated with ICU mortality in patients mechanically ventilated with PCV mode, regardless of NMBA use.
9.Association between mechanical power and intensive care unit mortality in Korean patients under pressure-controlled ventilation
Jae Kyeom SIM ; Sang-Min LEE ; Hyung Koo KANG ; Kyung Chan KIM ; Young Sam KIM ; Yun Seong KIM ; Won-Yeon LEE ; Sunghoon PARK ; So Young PARK ; Ju-Hee PARK ; Yun Su SIM ; Kwangha LEE ; Yeon Joo LEE ; Jin Hwa LEE ; Heung Bum LEE ; Chae-Man LIM ; Won-Il CHOI ; Ji Young HONG ; Won Jun SONG ; Gee Young SUH
Acute and Critical Care 2024;39(1):91-99
Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. Methods: We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. Results: A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P<0.001). In logistic regression analysis, only MPPCV was significantly associated with ICU mortality (odds ratio, 1.090; 95% confidence interval, 1.029–1.155; P=0.003). There was no significant effect of the interaction between MPPCV and use of NMBA on ICU mortality (P=0.579). Conclusions: MPPCV is associated with ICU mortality in patients mechanically ventilated with PCV mode, regardless of NMBA use.
10.Small Multi-Gene DNA Panel Can Aid in Reducing the Surgical Resection Rate and Predicting the Malignancy Risk of Thyroid Nodules
Moon Young OH ; Hye-Mi CHOI ; Jinsun JANG ; Heejun SON ; Seung Shin PARK ; Minchul SONG ; Yoo Hyung KIM ; Sun Wook CHO ; Young Jun CHAI ; Woosung CHUNG ; Young Joo PARK
Endocrinology and Metabolism 2024;39(5):777-792
Background:
We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules.
Methods:
Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group).
Results:
In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P<0.001), and indeterminate nodules (23.5% vs. 68.2%, P<0.001). Malignancy risk was significantly different between the panel and control groups (81.5% vs. 63.9%, P=0.008) for all nodules.
Conclusion
Our panel aids in managing thyroid nodules by providing information on malignancy risk based on mutations, potentially reducing unnecessary surgery in benign nodules or patients with less aggressive malignancies.

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