• Annals of Surgical Treatment and Research
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• v.95 no.5
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• pp.267-277
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• 2018

Purpose: The aim of this study was to analyze survival outcomes in 1,000 consecutive liver transplantations (LTs) performed at a single institution from 1993 to April 2017. Methods: The study population was divided into 2 groups based on donor type: deceased donor LT (DDLT; n = 181, 18.1%) and living donor LT (LDLT; n = 819; 81.9%), and into 3 periods based on the number of cases (first 300 cases, middle 300 cases, last 400 cases). Results: Infection was the most common cause of death, accounting for 34.8% (95 of 273). Mortality due to hepatocellular carcinoma recurrence occurred most frequently between 1 and 5 years after transplantation. Mortality rate by graft rejection was highest between 5 and 10 years after transplantation. And mortality by de novo malignancy occurred most frequently after 10 years after transplantation. The patient survival rates for the entire population at 5 and 10 years were 74.7%, and 68.6%, respectively. There was no difference in survival rate between the LDLT and DDLT groups (P = 0.188). Cause of disease, disease severity, case period, and retransplantation had a significant association with patient survival (P = 0.002, P = 0.031, P = 0.003, and P = 0.024, respectively). Conclusion: Surgical techniques and perioperative management for transplant patients have improved and undergone standardization. Controlling perioperative infection and managing patients with HCC as LT candidates will result in better outcomes.

• Korean Journal of Transplantation
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• v.31 no.4
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• pp.200-206
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• 2017

Background: Risk factors for bone avascular necrosis (AVN), a common late complication after kidney transplantation (KT), are not well known. Methods: Patients that underwent living-donor KT at Asan Medical Center between January 2009 and July 2016 were included in this retrospective study to determine the incidence and risk factors for AVN after KT. Results: Among 1,570 patients that underwent living-donor KT, 33 (2.1%) developed AVN during a mean follow-up of 49.8±25.0 months. Additionally, AVN was diagnosed at a mean of 13.9±6.6 months after KT. The mean cumulative corticosteroid dose during the last follow-up in patients without AVN (9,108±3,400 mg) was higher than that that in patients with AVN (4,483±1,114 mg) until AVN development (P<0.01). More patients among those with AVN (n=4, 12.1%) underwent steroid pulse treatment because of biopsy-proven rejections during the first 6 months after KT than patients without AVN (n=68, 4.4%; P=0.04). Female (hazard ratio [HR], 2.29; P=0.04) and steroid pulse treatment during the first 6 months (HR, 2.31; P=0.02) were significant AVN risk factors as revealed by the Cox proportional multivariate analysis. However, no significant differences in rejection-free graft survival rates were observed between the two groups (P=0.67). Conclusions: Steroid pulse treatment within 6 months of KT and being female were independent risk factors for AVN development.

• Advances in nano research
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• v.14 no.6
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• pp.507-519
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• 2023

Postsurgical infections are caused by implant-related pathogenic microorganisms that lead to graft rejection. Hence, an intrinsically antibacterial material is required to produce a biocompatible biomaterial with osteogenic properties that could address this major issue. Hence, this current research aims to make strontium-doped hydroxyapatite nanorods (SrHANRs) via an ethylene diamine tetraacetic acid (EDTA)-enable microwave mediated method using Anodontia alba seashells for biomedical applications. This investigation also perceives that EDTA acts as a soft template to accomplish Sr-doping and mesoporous structures in pure hydroxyapatite nanorods (HANRs). The X-ray diffraction (XRD) and transmission electron microscopy (TEM) analysis reveals the crystalline and mesoporous structures, and Brunauer-Emmett-Teller (BET) indicates the surface area of all the samples, including pure HANRs and doped HANRs. In addition, the biocidal ability was tested using various implant-related infectious bacteria pathogens, and it was discovered that Sr-doped HANRs have excellent biocidal properties. Furthermore, toxicity evaluation using zebrafish reports the non-toxic nature of the produced HANRs. Incorporating Sr²⁺ ions into the HAp lattice would enhance biocompatibility, biocidal activity, and osteoconductive properties. As a result, the biocompatible HANRs materials synthesized with Sr-dopants may be effective in bone regeneration and antibacterial in-built implant applications.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.2
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• pp.238-247
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• 2024

Backgrounds/Aims: Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT. Methods: This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers. Results: Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups. Conclusions: The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.

• International Journal of Stem Cells
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• v.17 no.1
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• pp.59-69
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• 2024

Human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs), induced pluripotent stem cells, and somatic cell nuclear transfer (SCNT)-hESCs can permanently self-renew while maintaining their capacity to differentiate into any type of somatic cells, thereby serving as an important cell source for cell therapy. However, there are persistent challenges in the application of hPSCs in clinical trials, where one of the most significant is graft rejection by the patient immune system in response to human leukocyte antigen (HLA) mismatch when transplants are obtained from an allogeneic (non-self) cell source. Homozygous SCNT-hESCs (homo-SCNT-hESCs) were used to simplify the clinical application and to reduce HLA mismatch. Here, we present a xeno-free protocol that confirms the efficient generation of neural precursor cells in hPSCs and also the differentiation of dopaminergic neurons. Additionally, there was no difference when comparing the HLA expression patterns of hESC, homo-SCNT-hESCs and hetero-SCNT-hESCs. We propose that there are no differences in the differentiation capacity and HLA expression among hPSCs that can be cultured in vitro. Thus, it is expected that homo-SCNT-hESCs will possess a wider range of applications when transplanted with neural precursor cells in the context of clinical trials.

• The Korean Journal of Nuclear Medicine
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• v.34 no.6
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• pp.497-507
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• 2000

Purpose: We have examined the utility of $^{99m}Tc$-MAG3 perfusion indices for assessing renal graft function in early post-transplantation period. Materials and Methods: Our study included 80 renal transplant recipients (48 men and 32 women, mean age: 40.3 years). Diagnosis was based on biopsy, laboratory data and clinical course. Renal scintigraphy (RS) was obtained using 100 MBq of $^{99m}Tc$-MAG3 from 11 days to 23 days of kidney transplantation. We measured 5 indices in whole-kidney (WK) and cortical (C) renograms; Hilson's perfusion index (PI), transplant perfusion index (TP) and transplant function index (TF) as perfusion parameter, and the time to peak activity (Tmax) and the ratio of renal counts at 20 min to that at 3 min (K20/3) as functional parameter. Results: The diagnoses at the day of RS were normal graft (NG) in 44, acute rejection (AR) in 14, acute tubular necrosis (ATN) in 10, and Cyclosporine A nephrotoxicity (CsA) in 12. TP and TF were significantly decreased in AR, ATN and CsA, compared to those in NG. K20/3 of AR and ATN wore significantly greater than that of NG. WK-Tmax of AR was significantly longer than that of NG. K20/3 of AR and C-K20/3 of ATN were significantly prolonged relative to those of CsA. There were no statistically significant perfusion indices among complication groups. Conclusion: TP and TF reflecting microperfusion and initial tubular extraction are reliable in assessing graft function. However, it is required to correlate perfusion indices with functional indices and clinical course in differentiating from one another among complication groups.

• Journal of Chest Surgery
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• v.30 no.7
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• pp.733-738
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• 1997

Sequential bilateral lung transplantation may result in a variety of perioperative and postoperative complications, showing high perioperative morbidity and mortality rates. This research was performed to investigate the hemodynamic changes in adult mongrel dogs after bilateral reimplantation, two methods preferred for avoiding or minimizing graft rejection. The anterior portion of the pulmonary artery and the left atrium proximal to the superior and the inferior pulmonary veins were resected out and then re-anastomosed one hour later to prevent torsion or stenosis of the anastomotic site and the formation of a thrombosis in the left atrium. An everted suture technique was employed for the left atrium; An hour after the division, however, the main bronchus was tightly anastomose by interrupted sutures of No. 4-0 prolene in a telescope method. A modified I-C solution mixed with PGEI was infused into the cut portion of the pulmonary artery at the rate of 15 mllkglmin and at a pressure of 40 cmH20 for a total dosage of 70 mlfkg in order to preserve the transected lung. Topical cooling using wet gauzes soaked with cold I-C solution was performed for one hour to prevent ischemic lung injury. The above procedures are considered to be beneficial for achieving a satisfactory outcome for bilateral lung reimplantation.

• KSBB Journal
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• v.20 no.4
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• pp.278-284
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• 2005

An immunosuppressive agent, human cytotoxic T lymphocyte antigen 4 (hCTLA4), is used for the prevention of graft rejection and treatment of autoimmune diseases. hCTLA4-Ig, a CTLA4-immunoglobulin fusion protein, was produced and secreted from transgenic rice cell suspension cultures using rice a-amylase (RAmy3D) expression system. In this system, hCTLA4-Ig expression was regulated metabolically by sugar starvation. For the purpose of improving hCTLA4-Ig production, the effects of osmotic pressure was investigated in suspension cultures of transgenic rice cells. The highest production level was achieved at 40 mM sorbitol $(140\;mOsm{\cdot}kg^{-1}\;H_2O)$. Using the medium with 8 mM glucose, the level of hCTLA4-Ig in the medium reached 45.3 mg/L. By adjusting the osmotic pressure of induction medium, it was found that the hCTLA4-Ig production could be increased up to 2.1-fold compared with that in batch culture.

• Journal of Periodontal and Implant Science
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• v.44 no.5
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• pp.235-241
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• 2014

Purpose: Regulatory T cells (Tregs), expressing CD4 and CD25 as well as Foxp3, are known to play a pivotal role in immunoregulatory function in autoimmune diseases, cancers, and graft rejection. Dendritic cells (DCs) are considered the major antigen-presenting cells (APCs) for initiating these T-cell immune responses, of which $CD103^+$ DCs are derived from precursor human peripheral blood mononuclear cells (PBMCs). The aim of the present study was to evaluate the capacity of these PBMC-derived $CD103^+$ DCs to promote the differentiation of antigen-specific Tregs. Methods: Monocyte-derived DCs were induced from $CD14^+$ monocytes from the PBMCs of 10 healthy subjects. Once the $CD103^+$ DCs were purified, the cell population was enriched by adding retinoic acid (RA). Peptide numbers 14 and 19 of Porphyromonas gingivalis heat shock protein 60 (HSP60) were synthesized to pulse $CD103^+$ DCs as a tool for presenting the peptide antigens to stimulate $CD3^+$ T cells that were isolated from human PBMC. Exogenous interleukin 2 was added as a coculture supplement. The antigen-specific T-cell lines established were phenotypically identified for their expression of CD4, CD25, or Foxp3. Results: When PBMCs were used as APCs, they demonstrated only a marginal capacity to stimulate peptide-specific Tregs, whereas $CD103^+$ DCs showed a potent antigen presenting capability to promote the peptide-specific Tregs, especially for peptide 14. RA enhanced the conversion of $CD103^+$ DCs, which paralleled the antigen-specific Treg-stimulating effect, though the differences failed to reach statistical significance. Conclusions: We demonstrated that $CD103^+$ DCs can promote antigen-specific Tregs from naive T cells, when used as APCs for an epitope peptide from P. gingivalis HSP60. RA was an effective reagent that induces mature DCs with the typical phenotypic expression of CD103 that demonstrated the functional capability to promote antigen-specific Tregs.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.8009-8013
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• 2015

Background: Orthotopic organ transplantation, a treatment option for irreversible organ dysfunction according to organ failure, severe damaged organ or malignancy in situ, was usually accompanied with massive blood loss thus transfusion was required. We aimed to evaluate the adverse impact of blood transfusion on solid organ transplantation. Materials and Methods: From January, 2009 to December, 2014, patients who received orthotopic organ transplantation at Far Eastern Memorial Hospital medical center were enrolled. Clinical data regarding anemia status and red blood cell (RBC) transfusion before, during and after operation, as well as patient outcomes were collected for further univariate analysis. Results: A total of 105 patients who underwent orthotopic transplantation, including liver, kidney and small intestine were registered. The mean hemoglobin (Hb) level upon admission and before operation were $11.6{\pm}1.8g/dL$ and $11.7{\pm}1.7g/dL$, respectively; and the nadir Hb level post operation and the final Hb level before discharge were $8.3{\pm}1.6g/dL$ and $10.2{\pm}1.6g/dL$, respectively. The median units (interquartile range) of RBC transfusion in pre-operative, peri-operative and post-operative periods were 0 (0-0), 2 (0-12), and 2 (0-6) units, respectively. Furthermore, the median (interquartile range) length of hospital stay (LHS) from admission to discharge and from operation to discharge were 28 (17-44) and 24 (16-37) days, respectively. Both peri-operative and post-operative RBC transfusion were associated with longer LHS from admission to discharge and from operation to discharge. Furthermore, it increased the risk of post-operative septicemia. While peri-operative RBC transfusion elevated the risk of acute graft rejection in patients who received orthotopic transplantation. Conclusions: Worse outcome could be anticipated in those who had received massive RBC transfusion in transplantation operation. Hence, peri-operative RBC transfusion should be avoided as much as possible.