Publications by authors named "Sun Hee Park"

306 Publications

Single-Dose Toxicity Study on ML171, a Selective NOX1 Inhibitor, in Mice.

Biomed Res Int 2021 30;2021:5515478. Epub 2021 May 30.

Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Republic of Korea.

Background: ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the safety of ML171 after a single intraperitoneal (IP) injection in mice.

Methods: The toxicity of a single dose of ML171 was evaluated in 6-week-old Institute of Cancer Research (ICR) mice in a good laboratory practice (GLP) laboratory. Twenty-five mice of each sex were assigned to five groups: negative control, vehicle control, and 125, 250, and 500 mg/kg of ML171. All mice were acclimatized for one week before beginning the study. Mice received an IP injection of ML171 or vehicle. The general condition and mortality of the animals were observed. The mice were sacrificed to evaluate histopathology 14 days after the administration of ML171 or vehicle.

Results: Bodyweights were not significantly different in any group. Three males and one female died due to ML171 administration in the 500 mg/kg dose group. Autopsies of the surviving mice did not reveal any significant abnormalities after the injection of 125 mg/kg of ML171. However, the anterior lobe edge of the liver was thickened and adhesions between the liver and adjacent organs were observed in mice treated with 250 or 500 mg/kg of ML171. In addition, hypertrophy of centrilobular hepatocytes and inflammatory cell infiltration were observed after injection of 250 and 500 mg/kg of ML171.

Conclusion: Our results indicate that the lethal IP injection dose of ML171 is 500 mg/kg for both males and females. Mortality were not observed for lower doses of ML171. The safe dose of single IP ML171 in ICR mice was 250 mg/kg or less. Further studies are needed to confirm the safety of ML171 in the human body.
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http://dx.doi.org/10.1155/2021/5515478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181097PMC
May 2021

Status of antimicrobial stewardship programmes in Korean hospitals including small to medium-sized hospitals and the awareness and demands of physicians: a nationwide survey in 2020.

J Glob Antimicrob Resist 2021 Jun 18;26:180-187. Epub 2021 Jun 18.

Division of Infectious Diseases, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, 173 beon-gil, Bundang-gu, Seongnam 13620, Gyeonggi-do, South Korea.

Objectives: This study aimed to identify the status of antimicrobial stewardship programmes (ASPs) in small to medium-sized Korean hospitals as well as the awareness and demands about ASPs of physicians.

Methods: A questionnaire was designed based on a questionnaire from a previous nationwide survey in 2018 targeting large hospitals in Korea and modified to reflect the results of in-depth interviews with non-infectious diseases (IDs) physicians at secondary care hospitals. The survey targeted all hospitals with ≥150 beds in South Korea and was performed in May-June 2020. Only one ASP-associated physician per hospital participated in the survey.

Results: The survey response rate was 31.9% (217/680). ID specialists comprised the majority of medical personnel participating in ASPs in tertiary care hospitals. Conversely, in secondary and primary care hospitals there was no predominant medical personnel for ASPs and the median full-time equivalent was 0 for all types of medical personnel. Tertiary care hospitals, more than secondary and primary care hospitals, tended to perform ASP activities more actively. 'Workforce for ASPs', 'Establishment of healthcare fees for ASPs' and 'Development of tools for ASPs' were the most important required support for ASP improvement.

Conclusion: The level of ASP establishment was more limited in primary care hospitals than in secondary and tertiary care hospitals in Korea. To improve ASPs in Korean hospitals, a supporting workforce and the establishment of a healthcare fee for ASPs appear to be necessary.
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http://dx.doi.org/10.1016/j.jgar.2021.06.001DOI Listing
June 2021

Safety and immunogenicity of a seasonal quadrivalent influenza vaccine (GC3110A) in healthy participants aged ≥ 65 years.

Vaccine 2021 06 13;39(27):3621-3625. Epub 2021 May 13.

Division of Infectious Diseases, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Ewha Womans University, Seoul, Republic of Korea.

Background: Seasonal Influenza is still considered associated with seasonal morbidity and hospitalization in the elderly population. The World Health Organization (WHO) recommended seasonal quadrivalent influenza vaccine (QIV) to reduce burden of two currently circulating influenza B lineages. Until 2019 Korean National Immunization Program (NIP) recommended trivalent influenza vaccine (TIV) after ongoing debates on cost effectiveness of QIV for elderly population. Although influenza vaccine only showed modest effect on reducing influenza in elderly, this study aimed to evaluate the immunogenicity and safety of inactivated QIV in healthy participants ≥ 65 years of age.

Methods: A total of 274 healthy participants aged ≥ 65 years received a QIV. Seroconversion-based vaccine efficacy of 4 strains of seasonal influenza was assessed 21 days after vaccination and adverse events were monitored until 180 days after vaccination.

Results: The percentages of participants seroconverted after vaccination on HI antibody against each strain were 36.5% (99/271) to A/H1N1, 47.6% (129/271) to A/H3N2, 40.6% (110/271) to B Yamagata, and 49.1% (133/271) to B Victoria. The percentages of participants seroprotected after vaccination on HI antibody against each strain were 81.2% (220/271) to A/H1N1, 98.5% (267/271) to A/H3N2, 95.2% (258/271) to B Yamagata, and 93.7% (254/271) to B Victoria. There was no serious adverse event (SAE) related with the study vaccine.

Conclusion: The quadrivalent split influenza vaccine is expected to offer seroprotection against influenza A and both influenza B lineages even in the elderly population.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.001DOI Listing
June 2021

Estimating the basic reproductive number of varicella in South Korea incorporating social contact patterns and seroprevalence.

Hum Vaccin Immunother 2021 Apr 8:1-6. Epub 2021 Apr 8.

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

Varicella, which is caused by the varicella zoster virus (VZV), is a common infectious disease affecting children. Varicella vaccines have been used for decades; however, vaccination policies vary across countries because of differences in VZV epidemiology. The basic reproductive number transmissibility measure parameter, also differs from country to country. In this study for varicella was estimated in South Korea using the contact rate matrix derived from averaged POLYMOD contact data, the Korean population, and proportionality factor fitted to the Korean VZV seroprevalence for varicella in South Korea was estimated to be 5.67 (95% CI: 5.33, 6.33). Therefore, to reach the herd immunity threshold, the critical vaccine coverage should be greater than 82.4% with a perfect vaccine, or the primary vaccine failure proportion should be less than 17.6% with 100% coverage. Because of the relatively low seroconversion rate and rapidly waning immunity after one-dose vaccination in South Korea, the herd immunity threshold is difficult to attain with only a one-dose vaccine. Two doses of vaccination may be necessary to effectively interrupt varicella transmission and maintain herd immunity in South Korea. The study results can help guide the decision-making on an effective varicella vaccination policy in South Korea.
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http://dx.doi.org/10.1080/21645515.2021.1898917DOI Listing
April 2021

The impact of two-dose varicella vaccination on varicella and herpes zoster incidence in South Korea using a mathematical model with changing population demographics.

Vaccine 2021 04 1;39(18):2575-2583. Epub 2021 Apr 1.

Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

Background: In South Korea, one-dose varicella vaccination was introduced to the National Immunization Program in 2005, but varicella outbreaks have continued to occur. Therefore, a two-dose vaccination strategy is considered.

Methods: We developed an age-structured deterministic compartment model using Korean population projection data. The impact of adding a second dose of varicella vaccine on varicella and herpes zoster (HZ) epidemiology was assessed under four different vaccine effectiveness (VE) scenarios (base, moderate, lowest, highest) and the optimal timing of the second vaccine dose (18 months, 4, 5, or 6 years of age) was examined over the period 2020-2065.

Results: A two-dose vaccination schedule reduced the cumulative varicella incidence by > 90% compared to no vaccination, regardless of the VE. The additional reduction attributable to a second dose compared to a single dose was greatest (82%) with the lowest VE scenario. A second dose at 6 years of age reduced the varicella incidence at a population level, whereas a second dose at 18 months of age reduced the varicella incidence primarily in the target birth cohorts. Routine vaccination at the age of 18 months with a catch-up vaccination of 6-year-olds was the optimal strategy for birth cohort and population-level control. HZ incidence continued to increase under no vaccination scenario, which represents the effect of aging population. Under a two-dose scenario, the additional increase in HZ incidence attributable to the reduced exogenous boosting was small relative to a one-dose scenario and a further reduction in HZ cases was observed.

Conclusion: A two-dose varicella vaccination schedule would significantly reduce varicella and HZ incidence in the long term. A second dose at the age of 18 months with a catch-up vaccination of 6-year-olds would be optimal for controlling varicella in South Korea.
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http://dx.doi.org/10.1016/j.vaccine.2021.03.056DOI Listing
April 2021

Histopathologic and clinicopathologic classifications of antineutrophil cytoplasmic antibody-associated glomerulonephritis: a validation study in a Korean cohort.

Kidney Res Clin Pract 2021 Mar 24;40(1):77-88. Epub 2021 Mar 24.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: Antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) is a common cause of rapidly progressive glomerulonephritis and requires prompt and proper immunosuppressive therapy to improve renal prognosis. This study aimed to evaluate the predictive value of two different classifications for renal outcomes in Korean AAGN patients.

Methods: Ninety-two patients who were diagnosed with AAGN at two tertiary hospitals between 2004 and 2018 were retrospectively analyzed retrospectively. The histopathologic classification according to glomerular pathology and the clinicopathologic classification according to normal glomeruli ratio, degree of interstitial fibrosis/tubular atrophy, and baseline renal function were evaluated using the Cox proportional hazards model.

Results: Forty-five patients (48.9%) progressed to end-stage kidney disease (ESKD) during the observation period. The mean age was 61.0 ± 15.3 years, and most patients had myeloperoxidase-ANCA (93.5%). In the histopathologic classification, the best renal survival occurred in the focal class, whereas the sclerotic class had the worst renal survival (sclerotic class vs. focal class; adjusted hazard ratio [aHR], 5.05; 95% confidence interval [CI], 1.32-19.31; p = 0.018). The mixed class had intermediate renal outcomes (mixed class vs. focal class; aHR, 4.23; 95% CI, 1.23-14.58; p = 0.022). In the clinicopathologic classification, the high-risk group had poor renal outcomes compared with the low-risk group (aHR, 6.56; 95% CI, 1.25-34.26; p = 0.026), but renal outcomes did not differ between the low- and medium-risk groups.

Conclusion: In Korean AAGN patients, histopathologic and clinicopathologic classifications had predictive value for renal outcomes, especially in the sclerotic class or the high-risk group with higher risk of progression to ESRD despite treatment.
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http://dx.doi.org/10.23876/j.krcp.20.184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041633PMC
March 2021

Measles seroprevalence among healthcare workers in South Korea during the post-elimination period.

Hum Vaccin Immunother 2021 Mar 9:1-5. Epub 2021 Mar 9.

Infection Control Unit, Daejeon St. Mary's Hospital, The Catholic University of Korea, Daejeon, Republic of Korea.

During the measles epidemic in 2019, in-hospital transmission of measles contributed to more than two-thirds of measles cases in South Korea, where measles is declared eliminated. This study aimed to examine measles seropositivity among healthcare workers (HCWs) in South Korea to help develop an effective measles prevention strategy for hospital settings. Measles IgG titer was tested in 1,579 HCWs working in a university-affiliated hospital and the measles-containing vaccine (MCV) immunization records of 870 HCWs were identified. The overall seropositivity was 92.0%, but the seropositivity and antibody titers were significantly low among HCWs aged 20-25 years (78.6%) and among one-dose vaccine recipients (86.7%). Among two-dose recipients, seropositivity was lower among young HCWs who received two doses during their childhood than among those who received the catch-up vaccination as part of job requirements (70.3% vs. 98.0%). Among 87 seronegative HCWs who received two-dose MMR vaccination, the seroconversion rate was 98.9%. A considerable proportion of young HCWs were potentially susceptible to measles despite receiving the two-dose vaccination during childhood because of the waning immunity against measles in a country with measles-eliminated status. Serological screening for measles of newly employed HCWs and MCV immunization of seronegative HCWs appears to be an effective prevention strategy.
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http://dx.doi.org/10.1080/21645515.2021.1888623DOI Listing
March 2021

Effects of steroid therapy in patients with severe fever with Thrombocytopenia syndrome: A multicenter clinical cohort study.

PLoS Negl Trop Dis 2021 02 19;15(2):e0009128. Epub 2021 Feb 19.

Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Republic of Korea.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS.

Methods: A retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests.

Results: Overall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P < .001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score <14; 29.2 (95% CI 27.70-30.73] vs. 24.9 (95% CI 21.21-28.53], P = .022]. Survival times for the early steroid (≤5 days from the start of therapy after symptom onset), late steroid (>5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P = .005).

Conclusions: After steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score <14).
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http://dx.doi.org/10.1371/journal.pntd.0009128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928499PMC
February 2021

The impact of the Xpert MTB/RIF screening among hospitalized patients with pneumonia on timely isolation of patients with pulmonary tuberculosis.

Sci Rep 2021 Jan 18;11(1):1694. Epub 2021 Jan 18.

Infection Prevention and Control Unit, The Catholic University of Korea, Daejeon St. Mary's Hospital, Daejeon, Korea.

In South Korea where the tuberculosis (TB) burden is intermediate, the risk of in-hospital transmission of TB remains high. We conducted a retrospective cohort study of 244 inpatients diagnosed with pulmonary TB (2015-2018) to evaluate the impact of the Xpert MTB/RIF assay (Xpert) screening on timely isolation. TB screening was performed with smear microscopy and a polymerase chain reaction test, and the Xpert was additionally used from November 2016. Among all patients with pulmonary TB, the median time-to-isolation was significantly reduced (22.6 vs. 69.7 h; p < 0.001) and segmented regression analysis adjusting for the time trend showed a reduction in time-to-isolation with the introduction of the Xpert (- 39.3 h; 95% CI - 85.6, 7.0; p = 0.096). Among 213 patients who were timely screened (≤ 72 h after admission), time-to-isolation decreased significantly (- 38.2 h; 95% CI - 70.6, - 5.8; p = 0.021) with the introduction of the Xpert, and its decreasing trend continued. The Xpert provided a shorter turnaround time (4.8 vs. 49.1 h; p < 0.001) and higher sensitivity (76.6% vs. 47.8%; p < 0.001) than smear microscopy. Thus, the Xpert can be a useful screening test for pulmonary TB in real-life hospital settings with an intermediate TB burden.
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http://dx.doi.org/10.1038/s41598-020-79639-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814080PMC
January 2021

Hypertension and Electrolyte Disorders in Patients with COVID-19.

Electrolyte Blood Press 2020 Dec 28;18(2):23-30. Epub 2020 Dec 28.

Division of Nephrology, Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.

The worldwide coronavirus disease 2019 (COVID-19) pandemic is still in progress, but much remains unknown about the disease. In this article, we review the association of hypertension or the renin-angiotensin system (RAS) with COVID-19 and the correlation between electrolyte disorders and disease severity. Underlying hypertension is likely to be associated with severe or critical COVID-19, but the relationship is not clear owing to confounding factors. Angiotensin-converting enzyme 2 (ACE2) plays an important role in the non-classical RAS pathway and binds to a receptor binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The RAS blockade is known to increase ACE2 levels, but controversy remains regarding the effect of RAS blockade therapy in the course of COVID-19. Some reports have indicated a protective effect of RAS blockade on COVID-19, whereas others have reported an association of RAS blockade therapy with the occurrence of severe complications such as acute kidney injury and admission to the intensive care unit. Electrolyte disorders are not uncommon in patients with COVID-19, and severe COVID-19 has frequently shown hypokalemia, hyponatremia, and hypocalcemia. Electrolyte imbalances are caused by alteration of RAS, gastrointestinal loss, effects of proinflammatory cytokines, and renal tubular dysfunction by the invasion of SARS-CoV-2.
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http://dx.doi.org/10.5049/EBP.2020.18.2.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781764PMC
December 2020

Adverse impact of renin-angiotensin system blockade on the clinical course in hospitalized patients with severe COVID-19: a retrospective cohort study.

Sci Rep 2020 11 20;10(1):20250. Epub 2020 Nov 20.

Division of Infectious Disease, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.

The association between angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) and the risk of mortality in hospitalized patients with severe coronavirus disease 2019 (COVID-19) was investigated. This retrospective cohort study was performed in all hospitalized patients with COVID-19 in tertiary hospitals in Daegu, Korea. Patients were classified based on whether they received ACE-I or ARB before COVID-19 diagnosis. The analysis of the primary outcome, in-hospital mortality, was performed using the Cox proportional hazards regression model. Of 130 patients with COVID-19, 30 (23.1%) who received ACE-I or ARB exhibited an increased risk of in-hospital mortality (adjusted hazard ratio, 2.20; 95% confidence interval [CI], 1.10-4.38; P = 0.025). ACE-I or ARB was also associated with severe complications, such as acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR], 2.58; 95% CI, 1.02-6.51; P = 0.045) and acute kidney injury (AKI) (aOR, 3.06; 95% CI, 1.15-8.15; P = 0.026). Among the patients with ACE-I or ARB therapy, 8 patients (26.7%) used high equivalent doses of ACE-I or ARB and they had higher in-hospital mortality and an increased risk of ARDS and AKI (all, P < 0.05). ACE-I or ARB therapy in patients with severe COVID-19 was associated with the occurrence of severe complications and increased in-hospital mortality. The potentially harmful effect of ACE-I or ARB therapy may be higher in patients who received high doses.
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http://dx.doi.org/10.1038/s41598-020-76915-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680105PMC
November 2020

Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury.

Int J Mol Sci 2020 Nov 16;21(22). Epub 2020 Nov 16.

Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.

The protective effects of alpha-1 antitrypsin (AAT) in tacrolimus (TAC)-induced renal injury was evaluated in a rat model. The TAC group rats were subcutaneously injected with 2 mg/kg TAC every day for four weeks. The TAC with AAT group was cotreated with daily subcutaneous injections of TAC and intraperitoneal injections of AAT (80 mg/kg) for four weeks. The effects of AAT on TAC-induced renal injury were evaluated using serum biochemistry, histopathology, and Western blotting. The TAC injection significantly increased renal interstitial fibrosis, inflammation, and apoptosis as compared to the control treatment. The histopathological examination showed that cotreatment of TAC and AAT attenuated interstitial fibrosis (collagen, fibronectin, and α-SMA staining), and α-SMA expression in Western blotting was also decreased. Immunohistochemical staining for inflammation (osteopontin and ED-1 staining) revealed improved interstitial inflammation in the TAC with AAT group compared to that in the TAC group. The TAC treatment increased renal apoptosis compared to the control treatment, based on the results of increased immunohistochemical staining of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), increased caspase-3 activity, and lower Bcl-2 to Bad expression ratio. However, AAT cotreatment significantly changed these markers and consequently showed decreased apoptosis. AAT protects against TAC-induced renal injury via antifibrotic, anti-inflammatory, and antiapoptotic effects.
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http://dx.doi.org/10.3390/ijms21228628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696546PMC
November 2020

Lactoferrin Induces Tolerogenic Bone Marrow-Derived Dendritic Cells.

Immune Netw 2020 Oct 29;20(5):e38. Epub 2020 Jul 29.

Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3 induced Treg (iTreg) differentiation in ovalbumin-specific CD4 T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.
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http://dx.doi.org/10.4110/in.2020.20.e38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609161PMC
October 2020

A Novel KPC Variant KPC-55 in ST307 of Reinforced Meropenem-Hydrolyzing Activity.

Front Microbiol 2020 7;11:561317. Epub 2020 Oct 7.

Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea.

A novel carbapenemase (KPC) variant, KPC-55, produced by a ST307 strain was characterized. strain BS407 was recovered from an active surveillance rectal swab of a patient newly admitted to a general hospital in Busan, South Korea. Carbapenemase production was confirmed by the modified Hodge test, and the MICs of β-lactams were determined by the broth microdilution method. The whole genome was sequenced. Cloning and expression of the gene in and MIC determination were performed. The enzyme KPC-55 was used for kinetic assays against β-lactams and compared with the KPC-2 enzyme. The new allele of the gene had a T794A alteration compared to the gene, resulting in the amino acid substitution Y264N in the middle of the β9-sheet. Compared to the KPC-2-producing strain, the KPC-55-producing strain exhibited a lower level of resistance to most β-lactam drugs tested, however, the KPC-55 enzyme catalyzed aztreonam and meropenem at an increased efficiency compared to the catalytic activity of KPC-2. KPC subtypes could have varied phenotypes due to alterations in amino acid sequences, and such an unexpected resistance phenotype emphasizes the importance of detailed characterizations for the carbapenemase-producing Enterobacterales.
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http://dx.doi.org/10.3389/fmicb.2020.561317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579404PMC
October 2020

Photoconjugation of an Fc-Specific Peptide Enables Efficient DAR 2 Antibody-Drug Conjugate Formation.

Org Lett 2020 11 19;22(21):8419-8423. Epub 2020 Oct 19.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, South Korea.

Antibody-drug conjugates (ADCs) in current clinical usage have been constructed via the nonspecific conjugation of drugs to antibodies, rendering the manufacturing processes difficult. In this study, a high-affinity IgG Fc-binding peptide equipped with a photoreactive amino acid was developed and successfully conjugated to Glu-382 of trastuzumab in a site-specific manner. The resulting conjugate was employed to generate a DAR 2 ADC product using click chemistry.
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http://dx.doi.org/10.1021/acs.orglett.0c03049DOI Listing
November 2020

Impact of the Learning Curve on the Survival of Abdominal or Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer.

Cancer Res Treat 2021 Jan 12;53(1):243-251. Epub 2020 Oct 12.

Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.

Purpose: The objective of this study was to define the learning curve required to attain satisfactory oncologic outcomes of cervical cancer patients who were undergoing open or minimally invasive surgery for radical hysterectomy, and to analyze the correlation between the learning curve and tumor size.

Materials And Methods: Cervical cancer patients (stage IA-IIA) who underwent open radical hysterectomy (n=280) or minimal invasive radical hysterectomy (n=282) were retrospectively reviewed. The learning curve was evaluated using cumulative sum of 5-year recurrence rates. Survival outcomes were analyzed based on the operation period ("learning period," P1 vs. "skilled period," P2), operation mode, and tumor size.

Results: The 5-year disease-free and overall survival rates between open and minimally invasive groups were 91.8% and 89.0% (p=0.098) and 96.1% and 97.2% (p=0.944), respectively. The number of surgeries for learning period was 30 and 60 in open and minimally invasive group, respectively. P2 had better 5-year disease-free survival than P1 after adjusting for risk factors (hazard ratio, 0.392; 95% confidence interval, 0.210 to 0.734; p=0.003). All patients with tumors < 2 cm had similar 5-year disease-free survival regardless of operation mode or learning curve. Minimally invasive group presented lower survival rates than open group when tumors ≥ 2 cm in P2. Preoperative conization improved disease-free survival in patients with tumors ≥ 2 cm, especially in minimally invasive group.

Conclusion: Minimally invasive radical hysterectomy required more cases than open group to achieve acceptable 5-year disease-free survival. When tumors ≥ 2 cm, the surgeon's proficiency affected survival outcomes in both groups.
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http://dx.doi.org/10.4143/crt.2020.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811999PMC
January 2021

The Crucial Role of Xanthine Oxidase in CKD Progression Associated with Hypercholesterolemia.

Int J Mol Sci 2020 Oct 9;21(20). Epub 2020 Oct 9.

Division of Nephrology, Kyungpook National University Hospital, Daegu 41944, Korea.

In the present study, we investigated the effects of xanthine oxidase (XO) inhibition on cholesterol-induced renal dysfunction in chronic kidney disease (CKD) mice, and in low-density lipoprotein (LDL)-treated human kidney proximal tubule epithelial (HK-2) cells. ApoE knockout (KO) mice underwent uninephrectomy to induce CKD, and were fed a normal diet or high-cholesterol (HC) diet along with the XO inhibitor topiroxostat (1 mg/kg/day). HK-2 cells were treated with LDL (200 µg/mL) and topiroxostat (5 µM) or small interfering RNA against xanthine dehydrogenase (siXDH; 20 nM). In uninephrectomized ApoE KO mice, the HC diet increased cholesterol accumulation, oxidative stress, XO activity, and kidney damage, while topiroxostat attenuated the hypercholesterolemia-associated renal dysfunction. The HC diet induced cholesterol accumulation by regulating the expressions of genes involved in cholesterol efflux ( and ) and synthesis ( and ), which was reversed by topiroxostat. Topiroxostat suppressed the expressions of genes related to hypercholesterolemia-associated inflammation and fibrosis in the unilateral kidney. LDL stimulation evoked changes in the cholesterol metabolism, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and NF-κB pathways in HK-2 cells, which were mitigated by XO inhibition with topiroxostat or siXDH. These findings suggest that XO inhibition exerts renoprotective effects against hypercholesterolemia-associated kidney injury. XO could be a novel therapeutic target for hypercholesterolemia-associated kidney injury in uninephrectomized patients.
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http://dx.doi.org/10.3390/ijms21207444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589966PMC
October 2020

Idiopathic membranous nephropathy in older patients: Clinical features and outcomes.

PLoS One 2020 9;15(10):e0240566. Epub 2020 Oct 9.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: Various factors can affect renal and patient outcome in idiopathic membranous nephropathy (iMN). We aimed to identify predictors of renal and patient survival in patients with iMN, with a special focus on outcomes among older patients.

Methods: We retrieved data on 1,776 patients (mean age 53.0 ± 14.7 years; 1,075 [60.5%] males) diagnosed with iMN from the Korean GlomeruloNEphritis sTudy (KoGNET), a database compiled from 18 centers in Korea.

Results: The cohort included 428 (24.1%) patients over 65 years old. Compared to younger patients, this group had lower hemoglobin and serum albumin levels, a higher incidence of nephrotic-range proteinuria, and higher prevalences of hypertension and diabetes. At last follow-up, complete or partial remission rates were not significantly different between the older and younger groups. Older age (HR: 0.98, 95%CI: 0.97-0.99), elevated hemoglobin (HR: 0.82, 95%CI: 0.72-0.93), high serum albumin (HR: 0.66, 95%CI: 0.44-0.99), and a high estimated glomerular filtration rate (HR: 0.96, 95%CI: 0.95-0.97) at biopsy were good predictors of renal outcomes. Significant risk factors for patient survival were older age (HR: 1.04, 95%CI: 1.01-1.10) and hypertension at biopsy (HR: 2.76, 95%CI: 1.30-5.90).

Conclusions: Older patients with iMN had favorable renal outcomes, but poor patient survival, compared to younger patients. Prognostic information on outcomes in this study might be helpful for optimizing the management of patients with iMN.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240566PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546503PMC
December 2020

Medium cut-off dialyzer improves erythropoiesis stimulating agent resistance in a hepcidin-independent manner in maintenance hemodialysis patients: results from a randomized controlled trial.

Sci Rep 2020 09 29;10(1):16062. Epub 2020 Sep 29.

Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.

The response to erythropoiesis stimulating agents (ESAs) is affected by inflammation linked to middle molecules in hemodialysis (HD) patients. We evaluated the effect of a medium cut-off (MCO) dialyzer on ESA resistance in maintenance HD patients. Forty-nine patients who underwent high-flux HD were randomly allocated to the MCO or high-flux group. The primary outcome was the changes of erythropoietin resistance index (ERI; U/kg/wk/g/dL) between baseline and 12 weeks. The MCO group showed significant decrease in the ESA dose, weight-adjusted ESA dose, and ERI compared to the high-flux group at 12 weeks (p < 0.05). The generalized estimating equation models revealed significant interactions between groups and time for the ESA dose, weight-adjusted ESA dose, and ERI (p < 0.05). Serum iron and transferrin saturation were higher in the MCO group at 12 weeks (p < 0.05). The MCO group showed a greater reduction in TNF-α and lower serum TNF-α level at 12 weeks compared to the high-flux group (p < 0.05), whereas no differences were found in the reduction ratio of hepcidin and serum levels of erythropoietin, erythroferrone, soluble transferrin receptor and hepcidin between groups. HD with MCO dialyzer improves ESA resistance over time compared to high-flux HD in maintenance HD patients. The MCO dialyzer provides superior removal of the inflammatory cytokine and thus improves iron metabolism in a hepcidin-independent manner.
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http://dx.doi.org/10.1038/s41598-020-73124-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524751PMC
September 2020

NOX1 Inhibition Attenuates Kidney Ischemia-Reperfusion Injury via Inhibition of ROS-Mediated ERK Signaling.

Int J Mol Sci 2020 Sep 21;21(18). Epub 2020 Sep 21.

Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.

The protective effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) 1 inhibition against kidney ischemia-reperfusion injury (IRI) remain uncertain. The bilateral kidney pedicles of C57BL/6 mice were clamped for 30 min to induce IRI. Madin-Darby Canine Kidney (MDCK) cells were incubated with HO (1.4 mM) for 1 h to induce oxidative stress. ML171, a selective NOX1 inhibitor, and siRNA against NOX1 were treated to inhibit NOX1. NOX expression, oxidative stress, apoptosis assay, and mitogen-activated protein kinase (MAPK) pathway were evaluated. The kidney function deteriorated and the production of reactive oxygen species (ROS), including intracellular HO production, increased due to IRI, whereas IRI-mediated kidney dysfunction and ROS generation were significantly attenuated by ML171. HO evoked the changes in oxidative stress enzymes such as SOD2 and GPX in MDCK cells, which was mitigated by ML171. Treatment with ML171 and transfection with siRNA against NOX1 decreased the upregulation of NOX1 and NOX4 induced by HO in MDCK cells. ML171 decreased caspase-3 activity, the Bcl-2/Bax ratio, and TUNEL-positive tubule cells in IRI mice and HO-treated MDCK cells. Among the MAPK pathways, ML171 affected ERK signaling by ERK phosphorylation in kidney tissues and tubular cells. NOX1-selective inhibition attenuated kidney IRI via inhibition of ROS-mediated ERK signaling.
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http://dx.doi.org/10.3390/ijms21186911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554761PMC
September 2020

Mupirocin and Chlorhexidine Genotypic Resistance Found in Staphylococcus aureus Isolated From Young Infants Below 90 Days Old: A Genetic Basis for Eradication Failure.

Pediatr Infect Dis J 2021 01;40(1):49-54

From the Division of Infectious Diseases, Departments of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Objectives: To investigate the genetic characteristics associated with eradication failure of Staphylococcus aureus in infants below 90 days old.

Methods: S. aureus isolated from clinical specimen cultures (blood, surgical tissue, or drainage, pus, etc.) and routine screening cultures in the neonatal intensive care unit (nasal and axillary skin swab) from patients below 90 days old were collected prospectively for 1 year, from August 2017 to July 2018. The isolates underwent typing and screening for genes associated with chlorhexidine (qacA/B), quaternary ammonium (smr), and mupirocin resistance (iles mutation, mupA, mupB), as well as Panton-Valentine leukocidin (PVL) toxin.

Results: During the study period, 40 nonduplicate isolates were included for analyses, of which 70.0% were methicillin-resistant S. aureus (MRSA). Mupirocin resistance was found in 25% of the total isolates; 17.4% of the colonizers; and 35.3% of the pathogens (P = 0.196). Chlorhexidine resistance gene was found in 3 MRSA isolates colonized in the nares of preterm infants. All isolates harbored the disinfectant quaternary ammonium compound (QAC) resistance gene. PVL toxin gene was found in 57.5%, and the presence of PVL gene among colonizers and pathogens was similar (69.6% vs. 41.2%, P = 0.072).

Conclusions: Mupirocin, chlorhexidine, and QAC-resistant MRSAs harboring the PVL toxin gene were found in the nasal carriages of preterm infants. In this highly vulnerable patient population, one-fourth of the isolates harbored mupirocin-resistant genes, and all were resistant to QAC disinfectants. These strains are associated with persistence in both carriage and environmental reservoirs within the hospitals.
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http://dx.doi.org/10.1097/INF.0000000000002882DOI Listing
January 2021

Development of Antibiotic Classification for Measuring Antibiotic Usage in Korean Hospitals Using a Modified Delphi Method.

J Korean Med Sci 2020 Aug 3;35(30):e241. Epub 2020 Aug 3.

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

In 2019, a project designed to develop a system for measuring and comparing antibiotic usage in hospitals was launched in Korea. As part of this project, we developed a means to classify antibiotic usage in Korean hospitals using a modified Delphi method. In results, the following categories of antibiotic classification were accepted for use in Korean hospitals: 1) broad-spectrum antibacterial agents predominantly used for hospital-onset infections in adults, 2) broad-spectrum antibacterial agents predominantly used for community-acquired infections in adults, 3) antibacterial agents predominantly used for resistant gram-positive infections in adults, 4) narrow-spectrum beta-lactam agents in adults, 5) antibacterial agents predominantly used for extensive antibiotic resistant gram-negative bacteria in adults, and 6) total antibacterial agents.
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http://dx.doi.org/10.3346/jkms.2020.35.e241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402924PMC
August 2020

Novel histopathologic predictors for renal outcomes in crescentic glomerulonephritis.

PLoS One 2020 27;15(7):e0236051. Epub 2020 Jul 27.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.

Introduction: Crescentic glomerulonephritis (CrGN) is a histologic feature of severe glomerular injury, clinically characterized by a rapid decline of renal function when not treated in a timely fashion. Factors associated with CrGN prognosis have not been thoroughly investigated. This study investigated the prognostic predictors of renal outcomes associated with CrGN, such as the histopathologic classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, arteriosclerosis, and tertiary lymphoid organ (TLO) formation.

Methods: A total of 114 patients diagnosed with CrGN between 2010 and 2018 at two university-based hospitals has been retrospectively analyzed. Relationships between potential predictors and renal outcomes were analyzed using Cox proportional hazards model and linear regression analysis.

Results: The mean age was 61.0 ± 15.3 years, and 49.1% were male. Among them, 92 (80.7%) and 11 (9.6%) patients were positive for ANCA and for anti-glomerular basement membrane antibody, respectively. During the median follow-up of 458.0 days, 55 patients (48.2%) had advanced to end-stage renal disease (ESRD). Cox proportional hazards analysis revealed that patients under the mixed and sclerotic classes had worse renal survival compared to those in the focal class (mixed: hazard ratio [HR], 3.74; 95% confidence interval [CI], 1.18 to 11.82; P = 0.025; sclerotic: HR, 4.84; 95% CI, 1.44 to 16.32; P = 0.011). Severe arteriosclerosis was also associated with poor renal survival (HR, 2.44; 95% CI, 1.04 to 5.77; P = 0.042). TLOs were observed in 41 patients (36.0%). Moreover, TLO formation was also a prognostic factor for ESRD (HR, 1.82; 95% CI, 1.03 to 3.21; P = 0.040). In the multivariate linear regression analysis, age and sclerotic class were independent predictors for the change in estimated glomerular filtration rate during 1 year after biopsy.

Conclusions: Specific histopathologic findings, histopathologic classification, severity of arteriosclerosis, and TLO formation provide helpful information in predicting renal outcomes associated with CrGN.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236051PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384637PMC
September 2020

Personal Protective Equipment for Healthcare Workers during the COVID-19 Pandemic.

Authors:
Sun Hee Park

Infect Chemother 2020 Jun;52(2):165-182

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

The coronavirus disease (COVID-19) pandemic has posed a challenge for healthcare systems, and healthcare workers (HCWs) are at high risk of exposure. Protecting HCWs is of paramount importance to maintain continuous patient care and keep healthcare systems functioning. Used alongside administrative and engineering control measures, personal protective equipment (PPE) is the last line of defense and the core component of protection. Current data suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mainly transmitted through respiratory droplets and close contact. Airborne transmission may occur during aerosol-generating procedures. However, the modes of transmission still remain uncertain, especially regarding the possibility of airborne transmission when aerosol-generating procedures are not performed. Thus, there are some inconsistencies in the respiratory protective equipment recommended by international and national organizations. In Korea, there have been several modifications to PPE recommendations offering options in choosing PPE for respiratory and body protection, which confuses HCWs; they are often unsure what to wear and when to wear it. The choice of PPE is based on the risk of exposure and possible modes of transmission. The level of protection provided by PPE differs based on standards and test methods. Thus, understanding them is the key in selecting the proper PPE. This article reviews evidence on the mode of SARS-CoV-2 transmission, compares the current PPE recommendations of the World Health Organization with those in Korea, and discusses standard requirements and the proper selection of PPE.
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http://dx.doi.org/10.3947/ic.2020.52.2.165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335655PMC
June 2020

Tacrolimus trough levels higher than 6 ng/mL might not be required after a year in stable kidney transplant recipients.

PLoS One 2020 2;15(7):e0235418. Epub 2020 Jul 2.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.

Background: Little is known regarding optimal tacrolimus (TAC) trough levels after 1 year post-transplant in stable kidney transplant recipients (KTRs) who have not experienced renal or cardiovascular outcomes. This study aimed to investigate the effect of 1-year post-transplant TAC trough levels on long-term renal and cardiovascular outcomes and opportunistic infections in stable KTRs.

Methods: KTRs receiving TAC with mycophenolate-based immunosuppression who did not experience renal or cardiovascular outcomes within 1 year post-transplant were enrolled from a multicenter observational cohort study. Renal outcome was defined as a composite of biopsy-proven acute rejection, interstitial fibrosis and tubular atrophy, and death-censored graft loss. Cardiovascular outcome was defined as a composite of de novo cardiomegaly, left ventricular hypertrophy, and cardiovascular events. Opportunistic infections were defined as the occurrence of BK virus or cytomegalovirus infections.

Results: A total of 603 eligible KTRs were divided into the low-level TAC (LL-TAC) and high-level TAC (HL-TAC) groups based on a median TAC level of 5.9 ng/mL (range 1.3-14.3) at 1 year post-transplant. The HL-TAC group had significantly higher TAC trough levels at 2, 3, 4, and 5 years compared with the levels of the LL-TAC group. During the mean follow-up of 63.7 ± 13.0 months, there were 121 renal outcomes and 224 cardiovascular outcomes. In multivariate Cox regression analysis, LL-TAC and HL-TAC were not independent risk factors for renal and cardiovascular outcomes, respectively. No significant differences in the development of opportunistic infections and de novo donor-specific anti-human leukocyte antigen antibodies and renal allograft function were observed between the two groups.

Conclusions: TAC trough levels after 1 year post-transplant remained at a similar level until the fifth year after kidney transplantation and were not directly associated with long-term outcomes in stable Korean KTRs who did not experience renal or cardiovascular outcomes. Therefore, in Asian KTRs with a stable clinical course, TAC trough levels higher than approximately 6 ng/mL might not be required after a year of kidney transplantation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235418PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332007PMC
September 2020

Impact of Donor-Recipient Age Difference on Graft Function and Survival After Deceased Donor Kidney Transplantation.

Transplant Proc 2020 Dec 26;52(10):3074-3079. Epub 2020 Jun 26.

Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea. Electronic address:

Background: Donor-recipient age difference (DRAD) is one of the reasons why patients on kidney waiting lists refuse to receive the offered organ. However, its impact on deceased donor kidney transplantation (DDKT) outcomes is still controversial.

Methods: One hundred fifty-three kidney transplant recipients (KTRs) who received their first-time DDKT were enrolled. The KTRs were divided into groups by DRAD: group 1 (n = 74) (DRAD < 0) and group 2 (n = 79) (DRAD ≥ 0). The KTRs in group 2 were divided into 3 subgroups: DRAD 0 to 10 (n = 35), 10 to 20 (n = 32), and ≥ 20 (n = 12). The outcome measures included estimated glomerular filtration rate (eGFR), delayed graft function (DGF), acute rejection (AR), and graft and patient survival.

Results: There were no significant differences in clinical outcomes between group 1 and 2 except eGFR until 5 years after DDKT. Among the subgroups of group 2, DGF, AR, patient survival, and eGFR until 5 years showed no significant differences. However, graft survival was significantly different (P = .015); in addition, in the DRAD ≥ 20 subgroup, graft survival decreased compared with that in the DRAD 10 to 20 subgroup and DRAD 0 to 10 subgroup (P = .020, P = .012, respectively). In a multivariate Cox proportional hazards analysis, the DRAD ≥ 20 subgroup showed a higher risk for graft failure than the DRAD 0 to 10 subgroup.

Conclusions: Although donors were of the same age or older than recipients, DDKT showed acceptable graft outcomes. However, because donors over 20 years older than recipients showed a decreased graft survival, it might be important to consider this point in donor-recipient matching of DDKT.
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http://dx.doi.org/10.1016/j.transproceed.2020.02.163DOI Listing
December 2020

Mycophenolic Acid Trough Concentration and Dose Are Associated with Hematologic Abnormalities but Not Rejection in Kidney Transplant Recipients.

J Korean Med Sci 2020 Jun 22;35(24):e185. Epub 2020 Jun 22.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.

Background: Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C₀) and dose with renal transplant outcomes and adverse events.

Methods: This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C₀ of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections.

Results: No differences in MPA C₀ and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C₀ was significantly higher in patients with leukopenia ( = 0.021) and anemia ( = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia ( = 0.002) compared with those without thrombocytopenia. MPA C₀ ≥ 3.5 μg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR], 3.80; 95% confidence interval [CI], 1.24-11.64; = 0.019) and anemia (AOR, 5.90; 95% CI, 1.27-27.51; = 0.024). An MPA dose greater than the mean value of 1,188.8 mg/day was an independent risk factor for thrombocytopenia (AOR, 3.83; 95% CI, 1.15-12.78; = 0.029). However, an MPA dose less than the mean value of 1,137.3 mg/day did not increase the risk of BPAR.

Conclusion: Either a higher MPA C₀ or dose is associated with an increased risk of cytopenia, but neither a lower MPA C₀ nor dose is associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.
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http://dx.doi.org/10.3346/jkms.2020.35.e185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308135PMC
June 2020

ICT-based adherence monitoring in kidney transplant recipients: a randomized controlled trial.

BMC Med Inform Decis Mak 2020 06 10;20(1):105. Epub 2020 Jun 10.

Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, South Korea.

Background: Prior studies have explored the use of regular reminders to improve adherence among kidney transplant recipients (KTRs), but none have included real-time alarms about drug dosage, frequency, and interval. In the present study, we aimed to evaluate the efficacy and stability of an information and communication technology (ICT)-based centralized monitoring system for increasing medication adherence among Korean KTRs.

Methods: In this prospective, multicenter, randomized controlled study, enrolled KTRs were randomized to either the ICT-based centralized monitoring group or control group. The ICT-based centralized monitoring system alerted both patients and medical staff with texts and pill box alarms if there was a missed dose or a dosage/time error. We compared the two groups in terms of medication adherence and transplant outcomes over 6 months, and evaluated patient satisfaction with the ICT-based monitoring system.

Results: Among 114 enrolled KTRs, 57 were assigned to the ICT-based centralized monitoring group and 57 to the control group. The two groups did not significantly differ in mean adherence at each follow-up visit. The intrapatient variability of tacrolimus and mycophenolic acid levels, renal function, and adverse transplant outcomes did not differ between the intervention and control groups, or between the intervention group with feedback generation and the intervention group without feedback generation. Patients showed high overall satisfaction with the ICT-based centralized monitoring system, which significantly improved across the study period (p = 0.012).

Conclusions: Due to high baseline adherence, the ICT-based centralized monitoring system did not maximize medication adherence or enhance transplant outcomes among Korean KTRs. However, patients were highly satisfied with the system. Our results suggest that the ICT-based centralized monitoring system could be successfully applied in clinical trials.

Trial Registration: ClinicalTrials.gov, NCT03136588. Registered 20 April 2017 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12911-020-01146-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285710PMC
June 2020

Fatal Outcomes of COVID-19 in Patients with Severe Acute Kidney Injury.

J Clin Med 2020 Jun 3;9(6). Epub 2020 Jun 3.

Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea.

The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage; however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI; 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, = 0.005). There were 17 deaths (56.7%) among AKI patients; 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, < 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75-7.48), = 0.001; HR = 15.65 (95% CI = 2.43-100.64), = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.
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http://dx.doi.org/10.3390/jcm9061718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355571PMC
June 2020

Outcomes of COVID-19 among Patients on In-Center Hemodialysis: An Experience from the Epicenter in South Korea.

J Clin Med 2020 Jun 2;9(6). Epub 2020 Jun 2.

Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.

Patients with advanced chronic kidney disease (CKD) or who are on hemodialysis (HD) could have increased susceptibility to the 2019 coronavirus disease (COVID-19) given their pre-existing comorbidities, older age, compromised immune system, and regular visits to populated outpatient dialysis centers. This study included 14 consecutive patients on HD or with advanced CKD who initiated HD after being diagnosed with laboratory-confirmed COVID-19 from February to April 2020 in hospitals throughout Daegu, South Korea. The included patients, 42.9% of whom were men, had a mean age of 63.5 years. Four patients had a history of contact with a patient suffering from COVID-19. The most common symptom was cough (50.0%), followed by dyspnea (35.7%). The mean time from symptom onset to diagnosis and admission was 2.6 and 3.5 days, respectively. Patients exhibited lymphopenia and elevated inflammatory markers, including C-reactive protein and ferritin. Chest radiography findings showed pulmonary infiltration in 10 patients. All patients underwent regular HD in a negative pressure room and received antiviral agents. Four patients received mechanical ventilation and continuous renal replacement therapy at a median duration of 14.0 and 8.5 days, respectively. One patient underwent extracorporeal membrane oxygenation for three days. Among the 14 patients included, two died due to acute respiratory distress syndrome, nine were discharged from the hospital, and three remained hospitalized. Despite the high-risk conditions associated with worse outcomes, patients on HD did not exhibit extremely poor overall COVID-19 outcomes perhaps due to early diagnosis, prompt hospitalization, and antiviral therapy.
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http://dx.doi.org/10.3390/jcm9061688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355817PMC
June 2020