1.Post‑transplant cyclophosphamide plus anti‑thymocyte globulin decreased serum IL‑6 levels when compared with post‑transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation
Jeong Suk KOH ; Myung‑Won LEE ; Thi Thuy Duong PHAM ; Bu Yeon HEO ; Suyoung CHOI ; Sang‑Woo LEE ; Wonhyoung SEO ; Sora KANG ; Seul Bi LEE ; Chul Hee KIM ; Hyewon RYU ; Hyuk Soo EUN ; Hyo‑Jin LEE ; Hwan‑Jung YUN ; Deog‑Yeon JO ; Ik‑Chan SONG
Blood Research 2025;60():5-
Background:
Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023.
Results:
Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).
Conclusion
Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.
2.Post‑transplant cyclophosphamide plus anti‑thymocyte globulin decreased serum IL‑6 levels when compared with post‑transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation
Jeong Suk KOH ; Myung‑Won LEE ; Thi Thuy Duong PHAM ; Bu Yeon HEO ; Suyoung CHOI ; Sang‑Woo LEE ; Wonhyoung SEO ; Sora KANG ; Seul Bi LEE ; Chul Hee KIM ; Hyewon RYU ; Hyuk Soo EUN ; Hyo‑Jin LEE ; Hwan‑Jung YUN ; Deog‑Yeon JO ; Ik‑Chan SONG
Blood Research 2025;60():5-
Background:
Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023.
Results:
Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).
Conclusion
Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.
3.Post‑transplant cyclophosphamide plus anti‑thymocyte globulin decreased serum IL‑6 levels when compared with post‑transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation
Jeong Suk KOH ; Myung‑Won LEE ; Thi Thuy Duong PHAM ; Bu Yeon HEO ; Suyoung CHOI ; Sang‑Woo LEE ; Wonhyoung SEO ; Sora KANG ; Seul Bi LEE ; Chul Hee KIM ; Hyewon RYU ; Hyuk Soo EUN ; Hyo‑Jin LEE ; Hwan‑Jung YUN ; Deog‑Yeon JO ; Ik‑Chan SONG
Blood Research 2025;60():5-
Background:
Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023.
Results:
Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).
Conclusion
Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.
4.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
5.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
6.The impact of severe depression on the survival of older patients with end-stage kidney disease
You Hyun JEON ; Jeong-Hoon LIM ; Yena JEON ; Yu-Kyung CHUNG ; Yon Su KIM ; Shin-Wook KANG ; Chul Woo YANG ; Nam-Ho KIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Jang-Hee CHO
Kidney Research and Clinical Practice 2024;43(6):818-828
Incidence of depression increases in patients with end-stage kidney disease (ESKD). We evaluated the association between depression and mortality among older patients with ESKD, which has not been studied previously. Methods: This nationwide prospective cohort study included 487 patients with ESKD aged >65 years, who were categorized into minimal, mild-to-moderate, and severe depression groups based on their Beck Depression Inventory-II (BDI-II) scores. Predisposing factors for high BDI-II scores and the association between the scores and survival were analyzed. Results: The severe depression group showed a higher modified Charlson comorbidity index value and lower serum albumin, phosphate, and uric acid levels than the other depression groups. The Kaplan-Meier curve revealed a significantly lower survival in the severe depression group than in the minimal and mild-to-moderate depression groups (p = 0.011). Multivariate Cox regression analysis confirmed that severe depression was an independent risk factor for mortality in the study cohort (hazard ratio, 1.39; 95% confidence interval, 1.01–1.91; p = 0.041). Additionally, BDI-II scores were associated with modified Charlson comorbidity index (p = 0.009) and serum albumin level (p = 0.004) in multivariate linear regression. Among the three depressive symptoms, higher somatic symptom scores were associated with increased mortality. Conclusion: Severe depression among older patients with ESKD increases mortality compared with minimal or mild-to-moderate depression, and patients with concomitant somatic symptoms require careful management of their comorbidities and nutritional status.
7.Effect of immunosuppressive agents on clinical outcomes in idiopathic membranous nephropathy
Ji-Young CHOI ; Ho Jun CHIN ; Hajeong LEE ; Yena JEON ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Jang-Hee CHO ; Chan-Duck KIM ; Yong-Lim KIM ; Sun-Hee PARK
Kidney Research and Clinical Practice 2024;43(5):635-647
Few comparative studies on the effects of immunosuppressants in patients with idiopathic membranous nephropathy have been conducted. Methods: Data from 489 patients who received conservative treatment or immunosuppressants were retrospectively analyzed by propensity score matching. Primary outcomes were complete or partial remission (CR or PR) of proteinuria, and secondary outcomes were renal survival and infection. Results: Of the 489 patients, 357 (73.0%) received immunosuppressants. Propensity score matching identified 82 patients from the conservative group and 82 patients in the immunosuppressant group. CR or PR at 12 months was significantly higher in the immunosuppressant group compared with the conservative group for the total population (p = 0.002) and the propensity score-matched population (p = 0.02). The use of immunosuppressants was significantly more effective with respect to achieving a CR or PR at 12 months in patients who were aged <65 years or female, or who had a proteinuria level of ≥4.0 g/g or an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 (p < 0.05). Renal survival was similar between patients receiving immunosuppressants and conservative treatment in both the total and matched populations. The immunosuppressant group (21.8%) had a significantly higher incidence of infections compared with the conservative group (13.6%) for the total population (p = 0.03), but statistical significance disappeared in the matched population (p > 0.99). Conclusion: The remission rate was significantly higher in the immunosuppressant group than in the conservative group, particularly in the subgroup of patients who were young or female, or those with heavy proteinuria loads or good renal function.
8.Observation of neutrophil extracellular traps in the development of diabetic nephropathy using diabetic murine models
You Hyun JEON ; Se-Hyun OH ; Soo-Jung JUNG ; Eun-Joo OH ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Chang-Won HONG ; Jang-Hee CHO
Laboratory Animal Research 2024;40(4):424-434
Background:
Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.
Results:
Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.
Conclusions
NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.
9.The impact of severe depression on the survival of older patients with end-stage kidney disease
You Hyun JEON ; Jeong-Hoon LIM ; Yena JEON ; Yu-Kyung CHUNG ; Yon Su KIM ; Shin-Wook KANG ; Chul Woo YANG ; Nam-Ho KIM ; Hee-Yeon JUNG ; Ji-Young CHOI ; Sun-Hee PARK ; Chan-Duck KIM ; Yong-Lim KIM ; Jang-Hee CHO
Kidney Research and Clinical Practice 2024;43(6):818-828
Incidence of depression increases in patients with end-stage kidney disease (ESKD). We evaluated the association between depression and mortality among older patients with ESKD, which has not been studied previously. Methods: This nationwide prospective cohort study included 487 patients with ESKD aged >65 years, who were categorized into minimal, mild-to-moderate, and severe depression groups based on their Beck Depression Inventory-II (BDI-II) scores. Predisposing factors for high BDI-II scores and the association between the scores and survival were analyzed. Results: The severe depression group showed a higher modified Charlson comorbidity index value and lower serum albumin, phosphate, and uric acid levels than the other depression groups. The Kaplan-Meier curve revealed a significantly lower survival in the severe depression group than in the minimal and mild-to-moderate depression groups (p = 0.011). Multivariate Cox regression analysis confirmed that severe depression was an independent risk factor for mortality in the study cohort (hazard ratio, 1.39; 95% confidence interval, 1.01–1.91; p = 0.041). Additionally, BDI-II scores were associated with modified Charlson comorbidity index (p = 0.009) and serum albumin level (p = 0.004) in multivariate linear regression. Among the three depressive symptoms, higher somatic symptom scores were associated with increased mortality. Conclusion: Severe depression among older patients with ESKD increases mortality compared with minimal or mild-to-moderate depression, and patients with concomitant somatic symptoms require careful management of their comorbidities and nutritional status.
10.Effect of immunosuppressive agents on clinical outcomes in idiopathic membranous nephropathy
Ji-Young CHOI ; Ho Jun CHIN ; Hajeong LEE ; Yena JEON ; Jeong-Hoon LIM ; Hee-Yeon JUNG ; Jang-Hee CHO ; Chan-Duck KIM ; Yong-Lim KIM ; Sun-Hee PARK
Kidney Research and Clinical Practice 2024;43(5):635-647
Few comparative studies on the effects of immunosuppressants in patients with idiopathic membranous nephropathy have been conducted. Methods: Data from 489 patients who received conservative treatment or immunosuppressants were retrospectively analyzed by propensity score matching. Primary outcomes were complete or partial remission (CR or PR) of proteinuria, and secondary outcomes were renal survival and infection. Results: Of the 489 patients, 357 (73.0%) received immunosuppressants. Propensity score matching identified 82 patients from the conservative group and 82 patients in the immunosuppressant group. CR or PR at 12 months was significantly higher in the immunosuppressant group compared with the conservative group for the total population (p = 0.002) and the propensity score-matched population (p = 0.02). The use of immunosuppressants was significantly more effective with respect to achieving a CR or PR at 12 months in patients who were aged <65 years or female, or who had a proteinuria level of ≥4.0 g/g or an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 (p < 0.05). Renal survival was similar between patients receiving immunosuppressants and conservative treatment in both the total and matched populations. The immunosuppressant group (21.8%) had a significantly higher incidence of infections compared with the conservative group (13.6%) for the total population (p = 0.03), but statistical significance disappeared in the matched population (p > 0.99). Conclusion: The remission rate was significantly higher in the immunosuppressant group than in the conservative group, particularly in the subgroup of patients who were young or female, or those with heavy proteinuria loads or good renal function.

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