Publications by authors named "Byung Ha Chung"

379 Publications

Efficacy of additional periprostatic apex nerve block on pain in each of 12 transrectal prostate core biopsies: a retrospective study.

BMC Urol 2021 Sep 16;21(1):132. Epub 2021 Sep 16.

Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul, 06273, Republic of Korea.

Background: We identified pain variation according to prostate biopsy sites and compared differences in pain relief according to the site of periprostatic nerve block (PNB).

Methods: This retrospective study collected data from 312 patients who underwent transrectal prostate biopsies between January 2019 and August 2020. Patients were stratified into two groups according to the site of local anesthesia (base vs. base and apex PNB), with each block achieved with 2.5 cm of 2% lidocaine. Pain scores were assessed using the visual analog scale at the following time points: probe insertion, PNB at base, PNB at apex, each of the 12 core biopsy sites, and 15 min after biopsy. The results were analyzed using a linear mixed model.

Results: The average pain scores were significantly higher in the base-only PNB group than were those in the base and apex PNB group (3.88 vs 2.82, p < 0.001). In the base-only PNB group, the pain scores increased from base to apex (p < 0.001), and the pain at each site also gradually increased as the biopsy proceeded (p < 0.001). In contrast, in the base and apex PNB group, there was minor change in pain scores throughout the procedure.

Conclusions: The pain scores varied at each site during the prostate biopsy. The provision of a base and apex PNB provided greater pain relief than does base-only PNB during prostate biopsy.
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http://dx.doi.org/10.1186/s12894-021-00898-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447510PMC
September 2021

Alleviation of renal ischemia/reperfusion injury by exosomes from induced pluripotent stem cell-derived mesenchymal stem cells.

Korean J Intern Med 2021 Sep 16. Epub 2021 Sep 16.

Transplant Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background/aims: Renal ischemia followed by reperfusion (I/R) is a leading cause of acute kidney injury (AKI), which is closely associated with high morbidity and mortality. Studies have shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) exert powerful therapeutic effects in renal ischemia. However, the efficacy of iMSC-derived exosomes (iExo) on I/R injuries remains largely unknown.

Methods: Human iPSCs were differentiated into iMSCs using a modified one-step method. Ultrafiltration, combined with purification, was used to isolate iExo from iMSCs. iExo was administered following I/R injury in a mouse model. The effect of iExo on I/R injury was assessed through changes in renal function, histology, and expression of oxidative stress, inflammation, and apoptosis markers. Further, we evaluated its association with the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway.

Results: Mice subjected to I/R injury exhibited typical AKI patterns; serum creatinine level, tubular necrosis, apoptosis, inflammatory cytokine production, and oxidative stress were markedly increased compared to sham mice. However, treatment with iExo attenuated these changes, significantly improving renal function and tissue damage, similar to the renoprotective effects of iMSCs on I/R injury. Significant induction of activated ERK 1/2 signaling molecules was observed in mice treated with iExo compared to those in the I/R injury group.

Conclusions: The present study demonstrates that iExo administration ameliorated renal damage following I/R, suggesting that iMSC-derived exosomes may provide a novel therapeutic approach for AKI treatment.
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http://dx.doi.org/10.3904/kjim.2020.438DOI Listing
September 2021

Tacrolimus Decreases Cognitive Function by Impairing Hippocampal Synaptic Balance: a Possible Role of Klotho.

Mol Neurobiol 2021 Aug 25. Epub 2021 Aug 25.

Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, The College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

The influence of long-term tacrolimus treatment on cognitive function remains to be elucidated. Using a murine model of chronic tacrolimus neurotoxicity, we evaluated the effects of tacrolimus on cognitive function, synaptic balance, its regulating protein (Klotho), and oxidative stress in the hippocampus. Compared to vehicle-treated mice, tacrolimus-treated mice showed significantly decreased hippocampal-dependent spatial learning and memory function. Furthermore, tacrolimus caused synaptic imbalance, as demonstrated by decreased excitatory synapses and increased inhibitory synapses, and downregulated Klotho in a dose-dependent manner; the downregulation of Klotho was localized to excitatory hippocampal synapses. Moreover, tacrolimus increased oxidative stress and was associated with activation of the PI3K/AKT pathway in the hippocampus. These results indicate that tacrolimus impairs cognitive function via synaptic imbalance, and that these processes are associated with Klotho downregulation at synapses through tacrolimus-induced oxidative stress in the hippocampus.
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http://dx.doi.org/10.1007/s12035-021-02499-3DOI Listing
August 2021

Effects of intravenous iron therapy on mortality and hospitalization of hemodialysis patients: A prospective cohort study in Korea.

Clin Nephrol 2021 Aug 23. Epub 2021 Aug 23.

Iron replacement therapy is necessary for anemia treatment in patients with advanced chronic kidney disease. Intravenous (IV) iron therapy is an efficient method for iron replacement. However, there are concerns regarding its considerable side effects, including increased risks of infection or major adverse cardiovascular events (MACE). This is a longitudinal study from a multicenter prospective cohort study conducted in the Korean end-stage renal disease population. All-cause mortality, death due to infection or MACE, hospitalization due to infection or MACE, and all adverse event of death or hospitalization due to infection or MACE were compared according to the iron replacement methods during the first 3 months of enrollment. Among 1,680 hemodialysis patients, 29.3% of patients received IV iron therapy, and 38% of patients received oral iron therapy. During the median 632 days follow-up, all-cause mortality, mortality or hospitalization due to infection or MACE, and all adverse events did not differ among iron replacement groups. There were significant differences related to the risk of all adverse events among iron replacement therapies in the log-rank test and univariate Cox regression analysis only in the prevalent dialysis patients; however, the significance was lost in multivariate Cox regression analysis. Similar results were observed in the 1-year short-term outcome analysis. High-dose IV iron did not increase adverse outcomes. All-cause mortality or all adverse events due to infection or MACE were not higher with the current clinical regimen of IV iron replacement therapy than with oral or no iron therapy in Korean hemodialysis patients.
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http://dx.doi.org/10.5414/CN110042DOI Listing
August 2021

Effect of training and individual operator's expertise on prostate cancer detection through prostate biopsy: Implications for the current quantitative training evaluation system.

Investig Clin Urol 2021 Aug 10. Epub 2021 Aug 10.

Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea.

Purpose: This study was conducted to evaluate the relevance of training and experience to gaining expertise in prostate biopsy based on an assessment of outcomes from the performance of urology residents.

Materials And Methods: We retrospectively reviewed the medical records of 10,299 patients who underwent prostate biopsy by 50 operators under a unified urology residency program. The number of prostate biopsies performed by an operator for each patient was used as an indicator of operator experience. Residents were grouped into quartiles according to cancer detection rates in the first 50 and the last 50 procedures.

Results: Among 10,299 patients (median age, 67.5 years; median prostate-specific antigen [PSA], 7.04 ng/mL), the overall prostate cancer detection rate and that for patients with PSA <10.0 ng/mL were 37.0% and 25.9%, respectively. Operator experience was a significant predictor for cancer detection in patients with PSA <10.0 ng/mL. Cancer detection rates and the proportion of more advanced prostate cancers were higher in the last 50 cases than in the first 50 cases. Detection rates varied significantly among operator; residents with higher detection rates at training initiation showed even higher detection rates after additional training.

Conclusions: Training that adds to the cumulative experience of a trainee appears to play a meaningful role in improving cancer detection rates. The level of skill required to achieve mastery for independent practice may be assessed from the accuracy results of prostate biopsy procedures, and trainees with poor rates will require more technical training to improve precision.
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http://dx.doi.org/10.4111/icu.20210060DOI Listing
August 2021

Optimal duration of preoperative antibiotic treatment prior to ureteroscopic lithotripsy to prevent postoperative systemic inflammatory response syndrome in patients presenting with urolithiasis-induced obstructive acute pyelonephritis.

Investig Clin Urol 2021 Aug 9. Epub 2021 Aug 9.

Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Purpose: There is no consensus on the optimal duration of preoperative antibiotic treatment prior to ureteroscopic lithotripsy in patients presenting with urolithiasis-induced obstructive acute pyelonephritis (APN). We aimed to identify surgeon-modifiable, preoperative risk factors associated with postoperative systemic inflammatory response syndrome (SIRS) in these patients.

Materials And Methods: This multicenter retrospective study evaluated 115 patients who presented with urolithiasis-induced obstructive APN between January 2008 and December 2019. All patients were administered intravenous third-generation cephalosporin until culture sensitivity confirmation or until ureteroscopic lithotripsy. Data were collected for age, sex, diabetes mellitus, performance status, stone features, hydronephrosis grade, preoperative renal collecting system drainage, laboratory data, operative time, and duration of preoperative antibiotic treatment. Sensitivity analysis using Youden's index and logistic regression analysis were used to assess risk factors of postoperative SIRS.

Results: Postoperative SIRS was identified in 32 (27.8%) patients. The incidence of postoperative SIRS was higher in patients who received preoperative antibiotic treatment for fewer than 14 days (38.8% vs. 12.5%; p=0.001). Backward variable selection logistic regression analysis revealed maximal stone diameter ≥15 mm, duration of preoperative antibiotic treatment <14 days, and preoperative C-reactive protein (CRP) level ≥6.0 mg/L to be associated with higher risk of postoperative SIRS.

Conclusions: Patients with urolithiasis-induced obstructive APN planned for ureteroscopic lithotripsy should be administered at least 14 days of preoperative antibiotic administration and achieve a serum CRP level ≤6.0 mg/L to minimize the risk of postoperative SIRS.
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http://dx.doi.org/10.4111/icu.20210160DOI Listing
August 2021

Clinical experience with active surveillance protocol using regular magnetic resonance imaging instead of regular repeat biopsy for monitoring: A study at a high-volume center in Korea.

Prostate Int 2021 Jun 5;9(2):90-95. Epub 2020 Dec 5.

Department of Urology, Yonsei University College of Medicine, Seoul, Korea.

Background: Here, we report the experience of a multiparameter magnetic resonance imaging (MRI)-based active surveillance (AS) protocol that did not include performing a repeat biopsy after the diagnosis of prostate cancer by prostate biopsy or transurethral resection of prostate.

Methods: From January 2010 to December 2017, we reviewed 193 patients with newly diagnosed prostate cancer who were eligible for AS. The patients were divided into AS group (n = 122) and definitive treatment group (n = 71) based on initial treatment. Disease progression was defined as a remarkable change in MRI findings. To confirm the stability of protocol, we compared the clinicopathological characteristics of patients who initially underwent radical prostatectomy (RP) (n = 58) and RP after termination of AS (n = 20).

Results: Among patients who initially selected AS (median adherence duration = 31.4 months), 70 (57.3%) subsequently changed their treatment options. Disease progression (n = 30) was the main cause for termination. No significant differences were found in the clinicopathologic characteristics at initial diagnosis and pathologic outcomes between patients who initially underwent RP and those who chose RP after termination of AS. In a comparative analysis of diagnostic methods, the patients with incidental prostate cancer by transurethral resection of prostate had higher age, lower prostate-specific antigen level and density, as well as longer AS adherence duration and follow-up duration compared with those diagnosed by prostate biopsy.

Conclusions: Our AS monitoring protocol, which depends on MRI instead of regular repeat biopsy, was feasible. Patients with incidental prostate cancer continued AS more compared with patients diagnosed by prostate biopsy.
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http://dx.doi.org/10.1016/j.prnil.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322812PMC
June 2021

Synergistic impact of pre-sensitization and delayed graft function on allograft rejection in deceased donor kidney transplantation.

Sci Rep 2021 08 9;11(1):16095. Epub 2021 Aug 9.

Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, South Korea.

The aim of this study is to investigate whether or not delayed graft function (DGF) and pre-transplant sensitization have synergistic adverse effects on allograft outcome after deceased donor kidney transplantation (DDKT) using the Korean Organ Transplantation Registry (KOTRY) database, the nationwide prospective cohort. The study included 1359 cases between May 2014 and June 2019. The cases were divided into 4 subgroups according to pre-sensitization and the development of DGF post-transplant [non-pre-sensitized-DGF(-) (n = 1097), non-pre-sensitized-DGF(+) (n = 127), pre-sensitized-DGF(-) (n = 116), and pre-sensitized-DGF(+) (n = 19)]. We compared the incidence of biopsy-proven allograft rejection (BPAR), time-related change in allograft function, allograft or patient survival, and post-transplant complications across 4 subgroups. The incidence of acute antibody-mediated rejection (ABMR) was significantly higher in the pre-sensitized-DGF(+) subgroup than in other 3 subgroups. In addition, multivariable cox regression analysis demonstrated that pre-sensitization combined with DGF is an independent risk factor for the development of acute ABMR (hazard ratio 4.855, 95% confidence interval 1.499-15.727). Moreover, DGF and pre-sensitization showed significant interaction (p-value for interaction = 0.008). Pre-sensitization combined with DGF did not show significant impact on allograft function, and allograft or patient survival. In conclusion, the combination of pre-sensitization and DGF showed significant synergistic interaction on the development of allograft rejection after DDKT.
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http://dx.doi.org/10.1038/s41598-021-95327-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352860PMC
August 2021

Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial.

Asian J Androl 2021 Jul 13. Epub 2021 Jul 13.

Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
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http://dx.doi.org/10.4103/aja.aja_64_21DOI Listing
July 2021

Kidney transplantation in highly sensitized recipients.

Kidney Res Clin Pract 2021 Sep 25;40(3):355-370. Epub 2021 Jun 25.

Division of Nephrology, Department of Internal Medicine and Transplantation Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

In kidney transplantation (KT), overcoming donor shortage is particularly challenging in patients with preexisting donor-specific antibodies (DSAs) against human leukocyte antigen (HLA), called HLA-incompatible KT (HLAi KT), carrying the risk of rejection and allograft loss. Thus, it is necessary to accurately evaluate the degree of sensitization before HLAi KT, and undertake appropriate pretreatment strategies. To determine the degree of sensitization, complement-dependent cytotoxicity has been the only method employed; the development of a method using flow cytometry further improved the test sensitivity. However, these tests present disadvantages, including the need for living cells, with a solid-phase assay developed to resolve this problem. Currently, the method using Luminex (Luminex Corp.) is widely used in clinical practice. As this method measures DSAs using single antigen beads, it is possible to classify immunological risks by measuring the type and amount of DSAs. Furthermore, there have been major advances in methods that involve DSA removal before HLAi KT. In the early stages of desensitization, plasmapheresis and intravenous immunoglobulins were the main treatment methods employed; however, the introduction of CD20 monoclonal antibody and proteasome inhibitors further increased the success rate of desensitization. Currently, HLAi KT has been established as an important transplant method, but an understanding of DSAs and a novel desensitization treatment are warranted.
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http://dx.doi.org/10.23876/j.krcp.21.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476304PMC
September 2021

Post-transplant allograft outcomes according to mismatch between donor kidney volume and body size of recipients with pre-transplant diabetes mellitus.

Diabetes Res Clin Pract 2021 Aug 30;178:108934. Epub 2021 Jun 30.

Transplantation Research Center, Seoul St. Mary's Hospital, Seoul, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Republic of Korea. Electronic address:

Aims: The aim of this study was to investigate allograft outcomes when relatively small kidneys were donated to patients with pre-transplant diabetes mellitus (DM).

Methods: From January 2010 to December 2018, 788 cases of non-sensitized living donor kidney transplant recipient and donor pairs were enrolled. The subjects were divided into four groups according to the relative size of kidney and pre-transplant DM status: non-DM large kidney, non-DM small kidney, DM large kidney, and DM small kidney. We compared allograft outcomes between these four groups.

Results: The four groups did not show differences in the development of de novo donor-specific antibody and acute rejection. However, a significantly greater decline of allograft function and increased proteinuria were observed in the DM small kidney group. The highest death-censored graft loss rate (P = 0.008) was also observed in this group and the combination of relatively small kidney size and pre-transplant DM was an independent risk factor for death-censored graft loss. In addition, the relatively small kidney and pre-transplant DM showed significant interaction with each other.

Conclusions: The size mismatch between donated kidney volume and recipient body size should be considered in donor selection of patients with pre-transplant DM.
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http://dx.doi.org/10.1016/j.diabres.2021.108934DOI Listing
August 2021

Non-Invasive Diagnosis for Acute Rejection Using Urinary mRNA Signature Reflecting Allograft Status in Kidney Transplantation.

Front Immunol 2021 10;12:656632. Epub 2021 Jun 10.

Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.

Urine has been regarded as a good resource based on the assumption that urine can directly reflect the state of the allograft or ongoing injury in kidney transplantation. Previous studies, suggesting the usefulness of urinary mRNA as a biomarker of acute rejection, imply that urinary mRNA mirrors the transcriptional activity of the kidneys. We selected 14 data-driven candidate genes through a meta-analysis and measured the candidate genes using quantitative PCR without pre-amplification in the cross-sectional specimens from Korean kidney transplant patients. Expression of 9/14 genes (CXCL9, CD3ϵ, IP-10, LCK, C1QB, PSMB9, Tim-3, Foxp3, and FAM26F) was significantly different between acute rejection and stable graft function with normal pathology and long-term graft survival in 103 training samples. CXCL9 was also distinctly expressed in allografts with acute rejection in hybridization analysis. This result, consistent with the qPCR result, implies that urinary mRNA could reflect the magnitude of allograft injury. We developed an AR prediction model with the urinary mRNAs by a binary logistic regression and the AUC of the model was 0.89 in the training set. The model was validated in 391 independent samples, and the AUC value yielded 0.84 with a fixed manner. In addition, the decision curve analysis indicated a range of reasonable threshold probabilities for biopsy. Therefore, we suggest the urine mRNA signature could be used as a non-invasive monitoring tool of acute rejection for clinical application and could help determine whether to perform a biopsy in a recipient with increased creatinine.
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http://dx.doi.org/10.3389/fimmu.2021.656632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222723PMC
September 2021

Biomarker for recurrent immunoglobulin A nephropathy in kidney allografts: promising but still a long way to go.

Authors:
Byung Ha Chung

Kidney Res Clin Pract 2021 Jun 9;40(2):180-182. Epub 2021 Jun 9.

Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

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http://dx.doi.org/10.23876/j.krcp.21.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237127PMC
June 2021

Apalutamide plus Androgen Deprivation Therapy for Metastatic Castration-Sensitive Prostate Cancer: Analysis of Pain and Fatigue in the Phase 3 TITAN Study.

J Urol 2021 10 27;206(4):914-923. Epub 2021 May 27.

BC Cancer, Vancouver, British Columbia, Canada.

Purpose: We performed an exploratory analysis of prostate cancer-related pain and fatigue on health-related quality of life in patients with metastatic castration-sensitive prostate cancer receiving apalutamide (240 mg/day) or placebo, with continuous androgen deprivation therapy (ADT), in the phase 3, randomized, double-blind, placebo controlled TITAN trial (NCT02489318).

Materials And Methods: Patient-reported outcomes for pain and fatigue were evaluated using the Brief Pain Inventory-Short Form and Brief Fatigue Inventory. Time to deterioration (TTD) was estimated by Kaplan-Meier method; hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards model. General estimating equations for logistic regression estimated treatment-related differences in the likelihood of worsening pain or fatigue.

Results: Compliance for completing the Brief Pain Inventory-Short Form and Brief Fatigue Inventory was high (96% to 97%) in the first year. Median followup times were similar between treatments (19 to 22 months). Median pain TTD was longer with apalutamide than placebo for "pain at its least in the last 24 hours" (28.7 vs 21.8 months, respectively; p=0.0146), "pain interfered with mood" (not estimable vs 22.4 months; p=0.0017), "pain interfered with walking ability" (28.7 vs 20.2 months; p=0.0027), "pain interfered with relations" (not estimable vs 23.0 months; p=0.0139) and "pain interfered with sleep" (28.7 vs 20.9 months; p=0.0167). Likelihood for fatigue and worsening fatigue were similar between groups.

Conclusions: Patients with metastatic castration-sensitive prostate cancer receiving apalutamide plus ADT vs placebo plus ADT reported consistently favorable TTD of pain. No difference for change in fatigue was observed with apalutamide vs placebo.
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http://dx.doi.org/10.1097/JU.0000000000001841DOI Listing
October 2021

Impact of high body mass index on allograft outcomes in kidney transplant recipients with presensitization to human leukocyte antigen.

Kidney Res Clin Pract 2021 May 30;40(2):304-316. Epub 2021 Apr 30.

Transplantation Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: This study aimed to investigate whether high body mass index (BMI) and presensitization to human leukocyte antigen (HLA) in kidney transplant recipients (KTRs) affected allograft outcomes.

Methods: From January 2010 to December 2018, 1,290 kidney transplantations (KTs) were performed at the Seoul St Mary's Hospital. Of these, 682 cases of ABO-compatible living donor KT patients were enrolled. They were divided into four groups (low BMI-non-sensitized, high BMI-non-sensitized, low BMI-sensitized, and high BMI-sensitized) according to the median BMI value (22.7 kg/m2) and HLA presensitization status (anti-HLA antibody mean fluorescence intensity > 3,000). Short-term and long-term allograft outcomes were compared between groups.

Results: In the high BMI-sensitized group, the decline in allograft function was higher than that in the other three groups. Death-censored graft loss (DCGL) rates were highest in the high BMI-sensitized group (4 of 21 [19.0%], p = 0.04). In the multivariable Cox regression hazard regression model analysis, the hazard ratio (HR) for DCGL was intensified when high BMI and presensitization statuses were combined (HR, 3.75; p = 0.03); these statuses significantly interacted with each other (p-value for interaction = 0.008).

Conclusion: Our results suggest that presensitization to HLA and high BMI might have an interactive adverse impact on allograft outcomes in KTRs.
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http://dx.doi.org/10.23876/j.krcp.20.216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237112PMC
May 2021

Clinical significance of heart rate variability for the monitoring of cardiac autonomic neuropathy in end-stage renal disease patients.

Nutr Metab Cardiovasc Dis 2021 06 26;31(7):2089-2098. Epub 2021 Mar 26.

Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address:

Background And Aims: The aim of this study is to determine whether the measurement of continuous heart rate variability (HRV) is useful in the evaluation of cardiac autonomic neuropathy (CAN) in end-stage renal disease (ESRD) patients.

Methods And Results: This cross-sectional study was performed at Seoul St. Mary's hospital between June 2017 and February 2018. Seventy-seven ESRD patients, and 29 healthy controls (HCs) were asked to wear a continuous ambulatory HRV monitor for 24 h. General cardiac function was evaluated using transthoracic echocardiogram (TTE), pulse wave velocity (PWV), coronary calcium scoring (CCS), and 24-h ambulatory blood pressure monitoring (ABPM). HRV parameters of ESRD patients and HCs, and the correlation of HRV parameters with cardiovascular screening methods were observed. All HRV parameters were significantly decreased in ESRD patients compared to HCs (P < 0.001). In the correlation analysis between TTE results and HRV parameters, 24-h standard deviation of all N-N intervals (24SDNN), 24-h standard deviation of sequential 5-min N-N interval means (24DANN) and Low Frequency Power/High Frequency Power (LF/HF) ratio showed negative correlations with E/e', LAVI and TR velocity which are representative indices for the diastolic function of the heart (P < 0.05). HRV parameters showed negative correlations with baPWV, CCS, and 24-h ABPM results as well (P < 0.05). Hemoglobin and serum albumin showed positive correlations with HRV parameters, and glucose, BUN, creatinine, and iPTH levels showed negative correlations (P < 0.05).

Conclusion: Continuous HRV monitoring may be a useful tool for the evaluation of CAN in ESRD.
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http://dx.doi.org/10.1016/j.numecd.2021.03.016DOI Listing
June 2021

Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study.

J Clin Oncol 2021 Jul 29;39(20):2294-2303. Epub 2021 Apr 29.

Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.

Purpose: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover.

Methods: Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed.

Results: With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; < .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; < .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance ( < .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports.

Conclusion: The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.
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http://dx.doi.org/10.1200/JCO.20.03488DOI Listing
July 2021

Clinical predictors of recurrent cephalic arch stenosis and impact of the access flow reduction on the patency rate.

J Vasc Access 2021 Apr 10:11297298211008758. Epub 2021 Apr 10.

Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Objective: Despite the widespread use of conventional percutaneous transluminal angioplasty (PTA), recurrence of cephalic arch stenosis (CAS), and low patency rate after PTA remain challenging problem. We aimed to identify the clinical predictors of recurrence of CAS and evaluate the effect of the access flow reduction on the fistula patency rate in patients with recurrent CAS.

Methods: In 1118 angiographies of 220 patients with CAS, access circuit patency rates after PTA and potential clinical predictors of recurrence of CAS were assessed. The effect of the banding procedure was evaluated in terms of post-interventional primary patency rate, and the number of interventions per access-year.

Results: At 3, 6, and 12 months after the first PTA on CAS, the post-interventional access circuit primary patency rates were 68.8%, 40.5%, and 25.1%, respectively. High CV to CA ratio (the ratio of the maximal diameter of the distal cephalic vein to the diameter of the cephalic arch) (Hazard ratio (HR), 1.437; 95% confidence interval (CI), 1.036-1.992) and involvement of the proximal segment of cephalic arch (HR, 1.828; 95% CI, 1.194-2.801) were significant predictors of recurrent CAS. For those with recurrent CAS (>3 times/year) and an access flow rate >1.5 L/minute, endovascular banding procedure was performed. The banding procedure significantly reduced the number of interventions per access-year ( = 3.299,  = 0.005 and  = 2.989,  = 0.007, respectively). Post-interventional access circuit primary patency rate after banding was significantly higher than that before banding ( = 0.01).

Conclusions: High CV to CA ratio and involvement of the proximal segment of the cephalic arch are independent clinical predictors of recurrent CAS. Endovascular banding might delay recurrence of CAS in patients with high CV to CA ratio and high access flow.
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http://dx.doi.org/10.1177/11297298211008758DOI Listing
April 2021

Impact of acute kidney injury in deceased donors with high Kidney Donor Profile Index on posttransplant clinical outcomes: a multicenter cohort study.

Kidney Res Clin Pract 2021 Mar 5;40(1):162-174. Epub 2021 Mar 5.

Transplant Research Center, Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: This study evaluated the impact of acute kidney injury (AKI) on posttransplant clinical outcomes for deceased donor (DD) kidney transplantation (KT) using the Kidney Donor Profile Index (KDPI) system.

Methods: Overall, 657 kidney transplant recipients (KTRs) receiving kidneys from 526 DDs from four transplant centers were included. We divided them into the high and low KDPI donor groups by 65%, the KDPI score, and both groups were subdivided into the AKI-DDKT and non-AKI-DDKT subgroups according to AKI in DDs.

Results: There was no significant difference in the incidence of delayed graft function (DGF) between the high and low KDPI-KTR groups; however, the AKI-DDKT subgroup showed significantly higher incidence of DGF than the non-AKI-DDKT subgroup in both groups (p = 0.001, p < 0.001, respectively). The death-censored graft survival rate was significantly lower in the high KDPI-KTR group than in the low KDPI-KTR group (p = 0.005). Only in the high KDPI-KTR group, the death-censored graft survival rate was significantly lower in the KT from DDs with AKI stage 3 than KT from DDs with non-AKI or AKI stage 1 or 2 (p = 0.040). The interaction between AKI stage 3 in DDs and high KDPI on the allograft outcome was significant (p = 0.002).

Conclusion: KTs from DDs with AKI stage 3 showed an adverse impact on the allograft outcome in the high KDPI-KTR group. Therefore, DDs with a high KDPI score should be managed carefully so that severe AKI does not occur prior to KT.
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http://dx.doi.org/10.23876/j.krcp.20.083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041636PMC
March 2021

Clinical Trial of Allogeneic Mesenchymal Stem Cell Therapy for Chronic Active Antibody-Mediated Rejection in Kidney Transplant Recipients Unresponsive to Rituximab and Intravenous Immunoglobulin.

Stem Cells Int 2021 10;2021:6672644. Epub 2021 Feb 10.

Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.

Clinical trials of biologic agents for chronic active antibody-mediated rejection (CAMR) in kidney transplant recipients (KTRs) have been disappointing. We performed a clinical trial of mesenchymal stem cell (MSC) treatment in KTRs with CAMR unresponsive to rituximab and intravenous immunoglobulin. This study was a phase 1 clinical trial to confirm patient safety. Two patients with CAMR unresponsive to rituximab and intravenous immunoglobulin were included. Each patient received allogeneic MSCs for 4 cycles (1 × 10 cells/kg every other week) via the peripheral vein in the distal arm. We observed adverse events and renal function for 6 months after the final MSC infusion and analyzed changes in immunomodulatory parameters in the peripheral blood between the start of treatment and 3 months after the final MSC infusion. There were no serious adverse events during the study period. Renal function was stable during MSC treatment but gradually decreased between the final MSC infusion and the study endpoint (patient 1: creatinine levels ranged from 3.01 mg/dL to 7.81 mg/dL, patient 2: 2.87 mg/dL to 3.91 mg/dL). In peripheral blood sample analysis between the start of treatment and 3 months after the final MSC infusion, there were similar trends for immunomodulatory markers. Our study showed that there were no serious adverse events for six months after allogeneic MSC treatment in KTRs with CAMR refractory to rituximab and intravenous immunoglobulin, but further studies need to define the efficacy of MSC treatment in CAMR.
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http://dx.doi.org/10.1155/2021/6672644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892211PMC
February 2021

Human-induced pluripotent stem cell lines (CMCi006-A and CMCi007-A) from a female and male patient with Fabry disease carrying the same frameshift deletion mutation.

Stem Cell Res 2021 03 30;51:102214. Epub 2021 Jan 30.

Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, The College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea; Transplant Research Center, The College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, The College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea. Electronic address:

Human-induced pluripotent stem cell lines (hiPSCs) derived from the peripheral blood mononuclear cells (PBMCs) of a woman (CMCi007-A) and her son (CMCi006-A) diagnosed with Fabry disease (FD) caused by the frameshift deletion mutation c.969delC in the alpha-galactosidase A (GLA) gene were generated. These hiPSCs showed typical human embryonic stem cell-like morphology and expressed pluripotency-associated markers, and directly differentiated into all three germ-layers. Karyotyping showed normal 46, XY (CMCi006-A) and 46, XX (CMCi007-A). In summary, we generated novel patient-specific hiPSC lines from both a female and male containing the same mutation, which may provide additional insight into the pathophysiology of FD.
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http://dx.doi.org/10.1016/j.scr.2021.102214DOI Listing
March 2021

Generation of the human induced pluripotent stem cell lines (CMCi009-A) from a patient with Birt-Hogg-Dubé syndrome (BHD) with heterozygous frameshift deletion mutation c.1285delC of the FLCN gene.

Stem Cell Res 2021 03 29;51:102215. Epub 2021 Jan 29.

Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, The College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea; Transplant Research Center, The College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, The College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea. Electronic address:

The human-induced pluripotent stem cell lines (hiPSCs) (CMCi009), derived from peripheral blood mononuclear cells (PBMCs) of a 42-year-old woman who were diagnosed as Birt-Hogg-Dubé syndrome (BHD) caused by the frameshift deletion mutation c.1285delC in FCLN gene, was generated using synthetic mRNA. Generated hiPSCs showed a typical human embryonic stem cell like morphology and expressed all pluripotency-associated markers, and directly differentiated into all three germ layers. Karyotyping of generated iPSCs showed normal 46, XY (CMCi009-A) respectively. In summary, we generated a novel patient-specific hiPSCs line containing the same mutation of FLCN gene and it can be used to provide additional insights for BHD pathophysiology.
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http://dx.doi.org/10.1016/j.scr.2021.102215DOI Listing
March 2021

Effect of Everolimus with Low-Dose Tacrolimus on Development of New-Onset Diabetes After Transplantation and Allograft Function in Kidney Transplantation: A Multicenter, Open-Label, Randomized Trial.

Ann Transplant 2021 Jan 22;26:e927984. Epub 2021 Jan 22.

Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

BACKGROUND This randomized controlled trial aimed to investigate the effect of everolimus (EVL) with low-dose tacrolimus (Tac) on the development of post-transplantation diabetes mellitus (PTDM) in kidney transplantation (KT). MATERIAL AND METHODS Seventy-seven kidney transplant patients from 4 transplant centers were included. Patients were randomized to the "EVL group" (n=38) and the "TAC group" (n=39). The target Tac trough level was 2 to 5 ng/mL in the EVL group and 5 to 10 ng/mL in the TAC group. RESULTS The 1-year cumulative incidence of PTDM in all patients was 7.8%, and no difference was found between the 2 groups (P=0.0819). Insulin resistance measured with the homeostatic model assessment for insulin resistance showed a significant increase only in the TAC group (1.11 to 1.30, P=0.0492). Allograft rejection rate and estimated glomerular filtration rate (eGFR) follow-ups every 3 months were not significantly different between the 2 groups. However, the EVL group showed a significant increase in the mean eGFR at 9 months and 12 months after KT compared to the baseline value (P=0.0242 and 0.0491, respectively). The EVL group showed lower insulin resistance and higher allograft function in comparison to the TAC group. CONCLUSIONS EVL-based immunosuppressive therapy with lower Tac exposure could be a safer alternative for maintenance treatment.
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http://dx.doi.org/10.12659/AOT.927984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836319PMC
January 2021

Development and Validation of the Stent Tracking Algorithm Registry for Monitoring and Retrieving Forgotten Ureteral Stents.

J Endourol 2021 08 2;35(8):1130-1134. Epub 2021 Mar 2.

Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Forgotten ureteral stents are associated with safety issues, increased cost, and medicolegal disputes. Tracking ureteral stents is cumbersome because of the variety in placement periods. We developed and validated an electronic medical record (EMR) system-based algorithm for monitoring patients with ureteral stent placements. The Stent Tracking Algorithm Registry (STAR) is automatically activated once the physician enters the stent placement or replacement billing code into the EMR billing system. At 120 days, an overdue notification is generated and sent to the attending physician through an EMR pop-up dashboard and e-mail. The model is automatically deactivated when the stent of the corresponding laterality is removed. To validate the feasibility of STAR, we performed a retrospective review of 2194 patients who received stent placements between November 2006 and September 2019. Among 2194 patients, STAR retrospectively identified 354 (16.1%) patients suspected of harboring forgotten ureteral stents. A total of 12 (0.5%) patients actually had forgotten ureteral stents and were contacted for removal. A total of 124 (5.7%) patients were identified because of the omission of the stent removal billing code, whereas 209 (9.5%) patients were identified because of being lost to follow-up after referral to another health care facility or death. There were no cases in which STAR identified patients whose stents were removed or replaced at an appropriate time frame. STAR provides an efficient interface with which to prevent the occurrence of forgotten ureteral stents. This model can be integrated into any EMR system that utilizes coding algorithms.
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http://dx.doi.org/10.1089/end.2020.0560DOI Listing
August 2021

BAFF Inhibition Effectively Suppresses the Development of Anti-HLA.A2 Antibody in the Highly Sensitized Mouse Model.

Int J Mol Sci 2021 Jan 16;22(2). Epub 2021 Jan 16.

Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

B cell activating factor (BAFF) is a cytokine that plays a role in the survival, proliferation and differentiation of B cells. We proposed to observe the effects of BAFF inhibition on the humoral immune responses of an allosensitized mouse model using HLA.A2 transgenic mice. Wild-type C57BL/6 mice were sensitized with skin allografts from C57BL/6-Tg (HLA-A2.1)1Enge/J mice and were treated with anti-BAFF monoclonal antibody (mAb) (named Sandy-2) or control IgG1 antibody. HLA.A2-specific IgG was reduced in BAFF-inhibited mice compared to the control group (Δ-13.62 vs. Δ27.07, < 0.05). BAFF inhibition also resulted in increased pre-pro and immature B cell proportions and decreased mature B cells in the bone marrow ( < 0.05 vs. control). In the spleen, an increase in transitional B cells was observed with a significant decrease in marginal and follicular B cells ( < 0.05 vs. control). There was no significant difference in the proportions of long-lived plasma and memory B cells. Microarray analysis showed that 19 gene probes were significantly up- (>2-fold, < 0.05) or down-regulated (≤2-fold, < 0.05) in the BAFF-inhibited group. BAFF inhibition successfully reduced alloimmune responses through the reduction in alloantibody production and suppression of B cell differentiation and maturation. Our data suggest that BAFF suppression may serve as a useful target in desensitization therapy.
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http://dx.doi.org/10.3390/ijms22020861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830620PMC
January 2021

Water-soluble coenzyme Q10 provides better protection than lipid-soluble coenzyme Q10 in a rat model of chronic tacrolimus nephropathy.

Korean J Intern Med 2021 07 12;36(4):949-961. Epub 2021 Jan 12.

Transplant Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background/aims: Coenzyme Q10 (CoQ10), is a promising antioxidant; however, low bioavailability owing to lipid-solubility is a limiting factor. We developed water-soluble CoQ10 (CoQ10-W) and compared its effects with conventional lipid-soluble CoQ10 (CoQ10-L) in an experimental model of chronic tacrolimus (Tac) nephropathy.

Methods: CoQ10-W was developed from a glycyrrhizic-carnitine mixed layer CoQ10 micelle based on acyltransferases. Chronic nephropathy was induced in rats with 28-day Tac treatment; they were concomitantly treated with CoQ10-L or CoQ10-W. CoQ10 level in plasma and kidney were measured using liquid chromatography-mass spectrometry. CoQ10-W and CoQ10-L effects on Tac-induced nephropathy were assessed in terms of renal function, histopathology, oxidative stress, and apoptotic cell death. Their effects on cell viability and reactive oxygen species (ROS) production were assessed in cultured proximal tubular cells, human kidney 2 (HK-2) cells.

Results: The plasma CoQ10 level was significantly higher in the CoQ10-W group than in the CoQ10-L group. Tac treatment caused renal dysfunction, typical pathologic lesions, and oxidative stress markers. Serum creatinine was restored in the Tac + CoQ10-L or CoQ10-W groups compared with that in the Tac group. CoQ10-W administration reduced oxidative stress and apoptosis markers. Mitochondrial ultrastructure assessment revealed that the addition of CoQ10-L or CoQ10-W with Tac increased mitochondrial size and number than Tac treatment alone. In vitro investigations revealed that both CoQ10-L and CoQ10-W improved cell viability and reduced ROS production in the Tac-induced HK-2 cell injury.

Conclusion: CoQ10-W has a better therapeutic effect in Tac-induced renal injury than conventional CoQ10-L, possibly associated with improved CoQ10 bioavailability.
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http://dx.doi.org/10.3904/kjim.2020.211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273834PMC
July 2021

Generation of a human induced pluripotent stem cell line (CMCi002-A) from a patient with Gitelman's syndrome.

Stem Cell Res 2020 12 4;49:102110. Epub 2020 Dec 4.

Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, The College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea; Transplant Research Center, The College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, The College of Medicine, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul 06591, Republic of Korea. Electronic address:

We established a human induced pluripotent stem cells (hiPSC) line (CMCi002-A) from peripheral blood mononuclear cells (PBMCs) of 29-year-old male with Gitelman's syndrome (GIT) caused by the mutation of solute carrier family 12 member 3 (SLC12A3) gene using Sendai virus. The GIT-hiPSCs showed a typical human embryonic stem cell like morphology and expressed all pluripotency-associated markers, exhibited normal karyotype and were capable of differentiating into cells representative of three germ layers.
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http://dx.doi.org/10.1016/j.scr.2020.102110DOI Listing
December 2020

Role of Renal Replacement Therapy During the Peri-Transplant Period of Heart Transplantation.

Ann Transplant 2020 Nov 24;25:e925648. Epub 2020 Nov 24.

Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

BACKGROUND Heart transplantation (HT) is the most useful treatment modality for heart failure. Although several studies have reported the impact of acute kidney injury (AKI) on clinical outcomes after transplantation, little is known about the impact of peri-transplant renal replacement therapy (RRT) on clinical outcomes. We compared the clinical outcomes according to RRT use status among patients with AKI during the peri-transplant period. MATERIAL AND METHODS The medical records of 21 patients who underwent HT from January 2006 to May 2019 were reviewed. We assessed the heart failure cause, comorbidities, immunosuppressant type, requirement for extracorporeal membrane oxygenation, AKI incidence, and cardiac and renal functions over time. The patients were divided into 3 groups: those without AKI (non-AKI group, n=6), those who underwent perioperative RRT (RRT group, n=10), and those who did not undergo RRT (non-RRT group, n=5). RESULTS The most common cause of HT was dilated cardiomyopathy (52.4%). Fifteen patients (71.4%) experienced AKI during the peri-transplant period. Among them, 9 (90%) in the RRT group underwent continuous RRT and only 1 (10%) underwent intermittent hemodialysis. Until 6 months after HT, the renal function of the RRT group was worse than that of the non-RRT group (estimated glomerular filtration rate 44.2 vs. 69.2 mL/min/1.73 m2, P=0.015), but the differences dissipated by 9 months. Finally, all patients, even in the RRT group, withdrew from dialysis. CONCLUSIONS RRT during the peri-transplant period in HT may be a good bridge therapy for renal function recovery in patients with cardiorenal AKI.
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http://dx.doi.org/10.12659/AOT.925648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697654PMC
November 2020

External Validation of the Long Short-Term Memory Artificial Neural Network-Based SCaP Survival Calculator for Prediction of Prostate Cancer Survival.

Cancer Res Treat 2021 Apr 6;53(2):558-566. Epub 2020 Oct 6.

Department of Urology, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Decision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality.

Materials And Methods: The validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)-free survival, cancer-specific survival (CSS), and overall survival (OS).

Results: Excellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation.

Conclusion: The SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.
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http://dx.doi.org/10.4143/crt.2020.637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053858PMC
April 2021
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