1.Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation
Soon Kyu LEE ; Ho Joong CHOI ; Young Kyoung YOU ; Pil Soo SUNG ; Seung Kew YOON ; Jeong Won JANG ; Jong Young CHOI
Clinical and Molecular Hepatology 2025;31(1):131-146
Background/Aims:
This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV).
Methods:
Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified.
Results:
Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05).
Conclusions
This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.
2.Prospective Multicenter Observational Study on Postoperative Quality of Life According to Type of Gastrectomy for Gastric Cancer
Sung Eun OH ; Yun-Suhk SUH ; Ji Yeong AN ; Keun Won RYU ; In CHO ; Sung Geun KIM ; Ji-Ho PARK ; Hoon HUR ; Hyung-Ho KIM ; Sang-Hoon AHN ; Sun-Hwi HWANG ; Hong Man YOON ; Ki Bum PARK ; Hyoung-Il KIM ; In Gyu KWON ; Han-Kwang YANG ; Byoung-Jo SUH ; Sang-Ho JEONG ; Tae-Han KIM ; Oh Kyoung KWON ; Hye Seong AHN ; Ji Yeon PARK ; Ki Young YOON ; Myoung Won SON ; Seong-Ho KONG ; Young-Gil SON ; Geum Jong SONG ; Jong Hyuk YUN ; Jung-Min BAE ; Do Joong PARK ; Sol LEE ; Jun-Young YANG ; Kyung Won SEO ; You-Jin JANG ; So Hyun KANG ; Bang Wool EOM ; Joongyub LEE ; Hyuk-Joon LEE ;
Journal of Gastric Cancer 2025;25(2):382-399
Purpose:
This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer.
Materials and Methods:
A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery.
Results:
Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064).
Conclusions
Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.
3.Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation
Soon Kyu LEE ; Ho Joong CHOI ; Young Kyoung YOU ; Pil Soo SUNG ; Seung Kew YOON ; Jeong Won JANG ; Jong Young CHOI
Clinical and Molecular Hepatology 2025;31(1):131-146
Background/Aims:
This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV).
Methods:
Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified.
Results:
Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05).
Conclusions
This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.
4.Prospective Multicenter Observational Study on Postoperative Quality of Life According to Type of Gastrectomy for Gastric Cancer
Sung Eun OH ; Yun-Suhk SUH ; Ji Yeong AN ; Keun Won RYU ; In CHO ; Sung Geun KIM ; Ji-Ho PARK ; Hoon HUR ; Hyung-Ho KIM ; Sang-Hoon AHN ; Sun-Hwi HWANG ; Hong Man YOON ; Ki Bum PARK ; Hyoung-Il KIM ; In Gyu KWON ; Han-Kwang YANG ; Byoung-Jo SUH ; Sang-Ho JEONG ; Tae-Han KIM ; Oh Kyoung KWON ; Hye Seong AHN ; Ji Yeon PARK ; Ki Young YOON ; Myoung Won SON ; Seong-Ho KONG ; Young-Gil SON ; Geum Jong SONG ; Jong Hyuk YUN ; Jung-Min BAE ; Do Joong PARK ; Sol LEE ; Jun-Young YANG ; Kyung Won SEO ; You-Jin JANG ; So Hyun KANG ; Bang Wool EOM ; Joongyub LEE ; Hyuk-Joon LEE ;
Journal of Gastric Cancer 2025;25(2):382-399
Purpose:
This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer.
Materials and Methods:
A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery.
Results:
Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064).
Conclusions
Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.
5.Optimal tacrolimus levels for reducing CKD risk and the impact of intrapatient variability on CKD and ESRD development following liver transplantation
Soon Kyu LEE ; Ho Joong CHOI ; Young Kyoung YOU ; Pil Soo SUNG ; Seung Kew YOON ; Jeong Won JANG ; Jong Young CHOI
Clinical and Molecular Hepatology 2025;31(1):131-146
Background/Aims:
This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV).
Methods:
Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified.
Results:
Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05).
Conclusions
This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.
6.Prospective Multicenter Observational Study on Postoperative Quality of Life According to Type of Gastrectomy for Gastric Cancer
Sung Eun OH ; Yun-Suhk SUH ; Ji Yeong AN ; Keun Won RYU ; In CHO ; Sung Geun KIM ; Ji-Ho PARK ; Hoon HUR ; Hyung-Ho KIM ; Sang-Hoon AHN ; Sun-Hwi HWANG ; Hong Man YOON ; Ki Bum PARK ; Hyoung-Il KIM ; In Gyu KWON ; Han-Kwang YANG ; Byoung-Jo SUH ; Sang-Ho JEONG ; Tae-Han KIM ; Oh Kyoung KWON ; Hye Seong AHN ; Ji Yeon PARK ; Ki Young YOON ; Myoung Won SON ; Seong-Ho KONG ; Young-Gil SON ; Geum Jong SONG ; Jong Hyuk YUN ; Jung-Min BAE ; Do Joong PARK ; Sol LEE ; Jun-Young YANG ; Kyung Won SEO ; You-Jin JANG ; So Hyun KANG ; Bang Wool EOM ; Joongyub LEE ; Hyuk-Joon LEE ;
Journal of Gastric Cancer 2025;25(2):382-399
Purpose:
This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer.
Materials and Methods:
A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery.
Results:
Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064).
Conclusions
Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.
7.Hypoxia‑inducible factor‑1α‑deficient adipose‑tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein‑1
Gi‑Sue KANG ; Young‑Eun KIM ; Ho Rim OH ; Hye‑Ju JO ; Seoyeon BOK ; Yoon Kyung JEON ; Gi Jeong CHEON ; Tae‑Young ROH ; Young‑Tae CHANG ; Do Joong PARK ; G‑One AHN
Laboratory Animal Research 2024;40(4):408-423
Background:
Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes.
Results:
In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals.
Conclusions
UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.
8.Hypoxia‑inducible factor‑1α‑deficient adipose‑tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein‑1
Gi‑Sue KANG ; Young‑Eun KIM ; Ho Rim OH ; Hye‑Ju JO ; Seoyeon BOK ; Yoon Kyung JEON ; Gi Jeong CHEON ; Tae‑Young ROH ; Young‑Tae CHANG ; Do Joong PARK ; G‑One AHN
Laboratory Animal Research 2024;40(4):408-423
Background:
Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes.
Results:
In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals.
Conclusions
UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.
9.Hypoxia‑inducible factor‑1α‑deficient adipose‑tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein‑1
Gi‑Sue KANG ; Young‑Eun KIM ; Ho Rim OH ; Hye‑Ju JO ; Seoyeon BOK ; Yoon Kyung JEON ; Gi Jeong CHEON ; Tae‑Young ROH ; Young‑Tae CHANG ; Do Joong PARK ; G‑One AHN
Laboratory Animal Research 2024;40(4):408-423
Background:
Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes.
Results:
In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals.
Conclusions
UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.
10.The Third Nationwide Korean Heart Failure III Registry (KorHF III):The Study Design Paper
Minjae YOON ; Eung Ju KIM ; Seong Woo HAN ; Seong-Mi PARK ; In-Cheol KIM ; Myeong-Chan CHO ; Hyo-Suk AHN ; Mi-Seung SHIN ; Seok Jae HWANG ; Jin-Ok JEONG ; Dong Heon YANG ; Jae-Joong KIM ; Jin Oh CHOI ; Hyun-Jai CHO ; Byung-Su YOO ; Seok-Min KANG ; Dong-Ju CHOI
International Journal of Heart Failure 2024;6(2):70-75
With advancements in both pharmacologic and non-pharmacologic treatments, significant changes have occurred in heart failure (HF) management. The previous Korean HF registries, namely the Korea Heart Failure Registry (KorHF-registry) and Korean Acute Heart Failure Registry (KorAHF-registry), no longer accurately reflect contemporary acute heart failure (AHF) patients. Our objective is to assess contemporary AHF patients through a nationwide registry encompassing various aspects, such as clinical characteristics, management approaches, hospital course, and long-term outcomes of individuals hospitalized for AHF in Korea. This prospective observational multicenter cohort study (KorHF III) is organized by the Korean Society of Heart Failure. We aim to prospectively enroll 7,000 or more patients hospitalized for AHF at 47 tertiary hospitals in Korea starting from March 2018. Eligible patients exhibit signs and symptoms of HF and demonstrate either lung congestion or objective evidence of structural or functional cardiac abnormalities in echocardiography, or isolated right-sided HF. Patients will be followed up for up to 5 years after enrollment in the registry to evaluate long-term clinical outcomes. KorHF III represents the nationwide AHF registry that will elucidate the clinical characteristics, management strategies, and outcomes of contemporary AHF patients in Korea.

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