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Background: Although non-teaching community hospitals form the majority of healthcare providers in South Korea, there is limited data on antibiotic usage in them. To evaluate the pattern of antibiotic usage and its appropriateness in hospitals with < 400 beds in South Korea. Methods: A multicentre retrospective study was conducted in 10 hospitals (six long-term care hospitals, three acute care hospitals, and one orthopaedic hospital), with < 400 beds in South Korea. We analysed patterns of antibiotic prescription in 2019, and their appropriateness in the participating hospitals. For the evaluation of the appropriateness of the prescription, 25 patients under antibiotic therapy were randomly selected at each hospital, over two separate periods. Due to the heterogeneity of their characteristics, the orthopaedics hospital was excluded from the analysis. Results: The most commonly prescribed antibiotics in long-term care hospitals was fluoroquinolone, followed by beta-lactam/beta-lactamase inhibitor (anti-pseudomonal). In acute care hospitals, these were third generation cephalosporin, followed by first generation cephalosporin, and second generation cephalosporin. The major antibiotics that were prescribed in the orthopedics hospital was first generation cephalosporin Only 2.3% of the antibiotics were administered inappropriately. In comparison, 15.3% of patients were prescribed an inappropriate dose. The proportion of inappropriate antibiotic prescriptions was 30.6% of the total antibiotic prescriptions. Conclusions: The antibiotic usage patterns vary between non-teaching community hospitals in South Korea. The proportion of inappropriate prescriptions exceeded 30% of the total antibiotic prescriptions. [ABSTRACT FROM AUTHOR]

Introduction: We studied the association between Henoch-Schönlein purpura nephritis (HSPN) and complement system activation. Methods: We retrospectively reviewed the pathologic findings and medical records of 35 children and 12 adults with HSPN and compared the differences according to C4d positivity in three groups consisting of total 47 patients, 35 pediatric and 12 adult patients, respectively. C4d staining of renal biopsy was additionally performed at the time of diagnosis or retrospectively using archival biopsy material. Results: The overall rate of C4d positivity was 53.2%: 20 (57.1%) of the 35 children and five (41.7%) of the 12 adults. Among the groups there was no significant difference in the severity of proteinuria, renal function, presence of crescents or mesangial proliferation stratified by C4d positivity, unlike IgA nephropathy. Conclusions: We suggest that the activation of complement system is not correlated with the clinical or pathological severity of HSPN. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Evodia, a fruit from Evodia rutaecarpa, has been used in oriental medicine, and since its various pharmaceutical actions, including anti-cancer activity, have become known, evodia has been widely used as a dietary supplement. However, information regarding its toxicity is limited. Materials and methods: Evodia fruit from Evodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang (0, 25, 74, 222, 667, and 2000mg/kg) was administered orally five times per week for 13 weeks. Clinical signs, body weight, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology, sperm morphology, organ weight, and gross and histopathological findings were evaluated. Results: Urinary ketone body excretion was detected in males at 667 and 2000mg/kg and in females at 2000mg/kg. An increase in absolute/relative liver weight was observed in both sexes at 2000mg/kg. Although levels of serum alanine aminotransferase, glucose, total cholesterol, and triglycerides were significantly reduced in males and/or females at 200 and/or 667 and 2000mg/kg, all values were within normal ranges and were considered non-adverse. In addition, no treatment-related differences in body weight, food consumption, hematology, vaginal cytology, sperm morphology, or gross and histopathological examination were detected. Conclusions: The subchronic no-observable-adverse-effect level for evodia fruit powder following oral administration in rats is greater than 2000mg/kg. [Copyright &y& Elsevier]

Summary: We evaluated the temporal trend of preemptive kidney transplantation (KT) and the effect of pretransplant dialysis duration on post‐transplant outcomes. This was a nationwide cohort study of the first‐time 3392 living donor KT (LDKT) recipients (2014–2019). The annual changes in proportion of preemptive KT, factors associated with preemptive KT, and post‐transplant outcomes were analyzed. Preemptive KT was performed in 816 (24.1%) patients. Annual trend analysis revealed gradual decrease in preemptive KT over time (P = 0.042). Among the underlying causes of preemptive KT, the proportion of diabetes increased and that of glomerulonephritis decreased during the study period. Glomerulonephritis as the primary renal disease was a predictor of preemptive KT. Patients with pretransplant dialysis >6 months showed increased graft failure risk than preemptive KT in the subdistribution of hazard model for competing risk (adjusted hazard ratio [aHR], 2.53; 95% confidence interval [CI], 1.09–5.87; P = 0.031) and in propensity score‐matched analysis (aHR, 2.45; 95% CI, 1.02–5.92; P = 0.034); however, pretransplant dialysis ≤6 months showed comparable graft survival with preemptive KT in both analyses. Preemptive KT declined over successive years, associated with an increase in diabetes and a decrease in glomerulonephritis as underlying causes of KT. Short period of dialysis less than 6 months does not affect graft survival compared with preemptive KT; however, longer dialysis decreases graft survival. [ABSTRACT FROM AUTHOR]

Summary: The smoking status of kidney transplant recipients and living donors has not been explored concurrently in a prospective study, and the synergistic adverse impact on outcomes remains uncertain. The self‐reported smoking status and frequency were obtained from recipients and donors at the time of kidney transplantation in a prospective multicenter longitudinal cohort study (NCT02042963). Smoking status was categorized as "ever smoker" (current and former smokers collectively) or "never smoker." Among 858 eligible kidney transplant recipients and the 858 living donors, 389 (45.3%) and 241 (28.1%) recipients were considered ever smokers at the time of transplant. During the median follow‐up period of 6 years, the rate of death‐censored graft failure was significantly higher in ever‐smoker recipients than in never‐smoker recipients (adjusted HR, 2.82; 95% CI 1.01–7.87; P = 0.048). A smoking history of >20 pack‐years was associated with a significantly higher rate of death‐censored graft failure than a history of ≤20 pack‐years (adjusted HR, 2.83; 95% CI 1.19–6.78; P = 0.019). No donor smoking effect was found in terms of graft survival. The smoking status of the recipients and donors or both did not affect the rate of biopsy‐proven acute rejection, major adverse cardiac events, all‐cause mortality, or post‐transplant diabetes mellitus. Taken together, the recipient's smoking status before kidney transplantation is dose‐dependently associated with impaired survival. [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19) has been spreading all over the world; however, its incidence and case-fatality ratio differ greatly between countries and between continents. We investigated factors associated with international variation in COVID-19 incidence and case-fatality ratio (CFR) across 107 northern hemisphere countries, using publicly available COVID-19 outcome data as of 14 September 2020. We included country-specific geographic, demographic, socio-economic features, global health security index (GHSI), healthcare capacity, and major health behavior indexes in multivariate models to explain this variation. Multiple linear regression highlighted that incidence was associated with ethnic region (p < 0.05), global health security index 4 (GHSI4) (beta coefficient [β] 0.50, 95% Confidence Interval [CI] 0.14–0.87), population density (β 0.35, 95% CI 0.10–0.60), and water safety level (β 0.51, 95% CI 0.19–0.84). The CFR was associated with ethnic region (p < 0.05), GHSI4 (β 0.53, 95% CI 0.14–0.92), proportion of population over 65 (β 0.71, 95% CI 0.19–1.24), international tourism receipt level (β − 0.23, 95% CI − 0.43 to − 0.03), and the number of physicians (β − 0.37, 95% CI − 0.69 to − 0.06). Ethnic region was the most influential factor for both COVID-19 incidence (partial R 2 = 0.545) and CFR (partial R 2 = 0.372), even after adjusting for various confounding factors. [ABSTRACT FROM AUTHOR]

We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients' blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset. [ABSTRACT FROM AUTHOR]

Abstract: Alkali earth selenide phosphor, SrSe:Eu2+ and Sr1−x Zn x Se:Eu2+, was prepared using a solid-state chemical reaction method. The synthesized phosphor displayed a broad excitation band, which is suitable for blue or near UV LED applications and emits green light (563nm). Zn2+ substitution for Sr2+ greatly enhances the green emission of the phosphors. The samples were also excited with various wavelength emitting diodes (410, 425, and 455nm) to assess their potential use as phosphors for white LED applications. The LED fabricated with the synthesized phosphor produced white light using blue LED with a CIE-1931 coordinate, T c and R a of (0.3199, 0.2777) 6499K and 49.7, respectively. [Copyright &y& Elsevier]

Abstract: Phosphor conversion white LED was developed using a 460nm InGaN LED chip as an excitation source and yellow emitting Ce-activated YAG as the phosphor. YAG:Ce phosphor was obtained through solid state reaction (SSR) at 1500°C, and spray pyrolysis (SP) at 900°C. The SSR and SP prepared YAG:Ce had strong excitation peaks at 460nm, and broad band emissions from 540nm to 580nm due to d–f transition of the Ce ion. The fabricated white LED using SSR-YAG:Ce and SP-YAG:Ce showed a luminous efficiency of 65.8lmW−1 with CRI of 65.1, and 92.1lmW−1 with CRI of 67.7 at 20mA, respectively. For high CRI values, CdSe/ZnSe nanoparticles emitting at 622nm were prepared via the wet chemical method. The high CRI values of the white LED were achieved by efficient energy transfer from YAG:Ce to CdSe/ZnSe nanoparticles in hybrid phosphor system. The luminous efficiency of the hybrid phosphor white LED was 77.1lmW−1 and this device showed an excellent CRI of 92.3 at 20mA. The CIE of the white LED was varied from (0.34, 0.31) to (0.35, 0.31) when the applied currents increased from 20 to 60mA. [ABSTRACT FROM AUTHOR]

Abstract: Gastrointestinal digestibility of new proteins inserted in food supply is one of significant parameters for assessing safety of genetically modified (GM) foods on the assumption that digestive stability is undesirable. Digestive stability of GM soybean was evaluated under the physiologically based in vitro digestion model. Electrophoresis was used to follow the in vitro sequential digestions/fermentation procedure and Western blotting was employed to confirm the new protein in GM soybean. CP4EPSPS newly expressed in GM soybean was completely digested in 15s in the gastric fluid in this model. In the assay of fermentation of new protein, CP4EPSPS was also complete degraded and no fermentation products were found during 24h of colon fermentation. Results from this study suggested that CP4EPSPS in GM soybean does not have a potential allergenicity due to its complete digestion within a very short time in gastric fluid. No formation of colonic protein fermentation products confirms that new protein is not capable of initiating colon cancer. [Copyright &y& Elsevier]

Abstract: To gauge the sensitivity of the female zebra finch song system to estradiol (E2), we used subcutaneous implants to administer various doses of E2 to hatchling female zebra finches. Four different doses of E2 were administered: 50, 15, 5 and 0-μg via subcutaneous silicon “ropes” at hatching, and the brains were examined in adulthood. Further, we examined whether masculinization was all-or-none once a threshold was reached or if the morphology of the song system would show a graded response to the various doses of E2. Finally, we asked if the various dependent measures – volume of song nuclei, neuron size, and neuron number – would show differential sensitivity to E2. Fifteen micrograms was sufficient to masculinize many aspects of the song system and was often as effective as 50-μg, causing a dramatic difference relative to the 0-μg group. Different aspects of the song system seemed differentially sensitive to the effects of E2: volumes of song control nuclei, the size of RA neurons, and the number of HVC neurons were significantly masculinized by 15-μg E2, but the number of RA neurons and HVC and lMAN soma sizes required 50-μg. The results suggest that several developmental processes are influenced by E2, possibly because of multiple sites of action or multiple processes that respond to E2. [Copyright &y& Elsevier]

Expression of TGF-β–induced matrix protein βig-h3 is up-regulated in the diabetic rat kidney and human proximal tubular epithelial cells treated with high glucose. Backgrounds. βig-h3 is an extracellular matrix protein whose expression in several cell types is greatly increased by transforming growth factor-β (TGF-β). TGF-β is believed to be involved in the development of diabetic nephropathy and thus we have assessed the possibility that βig-h3 may be a downstream molecule in this pathogenic process. Methods. Immunoblotting and immunohistochemistry were done using an antibody against mouse βig-h3 protein. βig-h3 and TGF-β concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Cell adhesion and migration were assessed by measuring activity of N -acetyl-β-d-glucosaminidase and using a transwell plate, respectively. Results. Immunohistochemistry revealed that βig-h3 occurs mainly in the basement membrane of proximal tubules, particularly the S3 segment but also to lesser extents in the basement membranes of the cortical thick ascending limb cells and the parietal glomerular epithelial cells in Bowman's capsule. Immunoblotting revealed that ∼68 kD bands were seen only in the cortex + the outer stripe of the outer medulla. Rats with streptozotocin (STZ)-induced diabetes exhibited a marked and sustained increase in renal βig-h3 abundance. This was mirrored by urinary βig-h3 levels. In vitro experiments with human primary renal proximal tubular epithelial cells revealed that their expression of βig-h3 was greatly increased by either TGF-β or glucose. High glucose levels also stimulated TGF-β production by renal proximal tubular epithelial cells and the high glucose–induced βig-h3 expression was almost completely blocked by anti-TGF-β antibody. βig-h3 mediated renal proximal tubular epithelial cells adhesion and migration. Conclusion. βig-h3 may be important in the development of diabetic nephropathy. Furthermore, the level of urinary βig-h3 may be useful as an early marker reflecting disease onset and progression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • DRAD is one of the major factors in determining organ acceptance in DDKT. • Although donors were of the same age or older than recipients, DDKT showed acceptable graft outcomes. • Donors more than 20 years older than recipients showed a decreased graft survival. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Thio-selenide phosphor, SrGa2SeS3:Eu2+, was prepared using a solid-state chemical reaction method without the addition of toxic gases or other excess materials. The synthesized phosphor displayed a broad excitation band, which is suitable for blue or NUV LED applications and emits green light (528nm). The samples were also excited with various wavelength emitting diodes (410nm, 425nm, and 455nm) to assess their potential use as phosphors for white LED applications. The LED fabricated with the synthesized phosphor produced bluish green light using NUV LED with a CIE-1931 coordinate, Tc and Ra of (0.2309, 0.3436), 11732.3K and 18.2, respectively. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Medium cut-off (MCO) dialyzers help remove larger middle molecules associated with symptoms related to the accumulation of uremic retention solutes. We investigated the effect of an MCO dialyzer on the improvement of quality of life (QOL) in maintenance hemodialysis (HD) patients. Forty-nine HD patients with high-flux dialysis were randomly assigned to either an MCO (Theranova 400, Baxter) or a high-flux (FX CorDiax 80 or 60, Fresenius Medical Care) dialyzer and completed the study. QOL was assessed at baseline and after 12 weeks of treatment using the Kidney Disease Quality of Life Short Form-36, and pruritus was assessed using a questionnaire and visual analog scale. The reduction ratios of middle molecules were also evaluated. Laboratory markers, including serum albumin, did not differ between the two groups after 12 weeks. Removals of kappa and lambda free light chains were greater for MCO dialyzer than high-flux dialyzer. The MCO group had higher scores than the high-flux group in the domains of physical functioning and physical role (75.2 ± 20.8 vs. 59.8 ± 30.1, P = 0.042; 61.5 ± 37.6 vs. 39.0 ± 39.6, P = 0.047, respectively), and the MCO group had lower mean scores for morning pruritus distribution and the frequency of scratching during sleep (1.29 ± 0.46 vs. 1.64 ± 0.64, P = 0.034; 0.25 ± 0.53 vs. 1.00 ± 1.47, P = 0.023, respectively). MCO dialyzers may improve patient-reported outcomes, particularly the physical components of QOL and uremic pruritus, in patients with high-flux dialyzers. [ABSTRACT FROM AUTHOR]

Background: Our study aim was to evaluate neuromuscular ultrasound (NMUS) for the assessment of taxane chemotherapy-induced peripheral neuropathy (CIPN), the dose-limiting toxicity of this agent.Methods: This cross-sectional study of breast cancer patients with taxane CIPN measured nerve cross-sectional area (CSA) by NMUS and compared with healthy historical controls. Correlations were determined between CSA and symptom scale, nerve conduction studies, and intraepidermal nerve fiber density (IENFD).Results: A total of 20 participants reported moderate CIPN symptoms at a median of 3.8 months following the last taxane dose. Sural nerve CSA was 1.2 mm2 smaller than healthy controls (P ≤ .01). Older age and time since taxane were associated with smaller sural nerve CSA. For each 1 mm2 decrease in sural nerve CSA, distal IENFD decreased by 2.1 nerve/mm (R2 0.30; P = .04).Conclusions: These data support a sensory predominant taxane neuropathy or neuronopathy and warrant future research on longitudinal NMUS assessment of CIPN. [ABSTRACT FROM AUTHOR]

Slow graft function (SGF) is considered to be an intermediate state between immediate graft function (IGF) and delayed graft function (DGF). However, the criteria of SGF is still arbitrary, and the clinical outcomes of SGF are not fully understood. A total of 212 deceased donor kidney transplantation recipients were enrolled. Three schemas were adopted, which classified SGF according to the serum creatinine (Cr) level by a given postoperative day (POD). SGF was defined as Cr ≥ 3.0 mg/dL on POD5, Cr ≥ 2.5 mg/dL on POD7, and Cr ≥ 1.5 mg/dL on POD14 without dialysis in schema I, II, and III, respectively. Estimated glomerular filtration rate (eGFR) after transplantation, acute rejection, and graft survival were compared in each schema. Decreased renal function, defined as eGFR less than 30.0 mL/min/1.73m2, was also compared. In schema I and III, SGF had significantly lower eGFR at 3 months after transplantation compared with IGF (P <. 017), and only schema III maintained the difference until 36 months after transplantation. The incidence of decreased renal function showed significant difference among groups in schema I and III (P <. 05). Graft survival did not show significant difference among groups in all schemas. However, SGF and DGF groups showed a higher probability of decreased renal function than the IGF group (P <. 017) in schema I and III. In deceased donor kidney transplantation, certain definitions of SGF identified significantly worse clinical outcomes compared with IGF, suggesting similar impact with DGF. It is necessary to reach a consensus on a clearer definition of SGF with further studies. [ABSTRACT FROM AUTHOR]

There is a high risk of fracture after kidney transplantation (KT). Recipients of KT are susceptible to persistent hyperparathyroidism and other disorders of bone and mineral metabolism. However, the risk factors for fractures after KT remain uncertain. The aim of the present study was to investigate the risk factors for fracture after KT. A total of 941 recipients of KT were enrolled from a multicenter observational cohort study in Korea from 2012 to 2016. The biochemical markers were measured at the time of KT, then annually for 5 years following KT. All fracture events were recorded. A Cox proportional hazards analysis was performed to calculate hazard ratios (HR) for the association of risk factors with fractures. Twenty-two fractures had occurred in 20 patients during the study period. Baseline and serial changes of mineral and bone biochemical markers were similar between fracture and nonfracture patient groups. Among the total study population, 104 patients were diagnosed with osteoporosis and 422 patients were diagnosed with osteopenia in a pretransplant bone mineral density test. In a multivariate Cox analysis, pretransplant osteoporosis (HR = 11.76; 95% confidence interval [CI], 2.28-60.69; P =. 003) and pretransplant osteopenia (HR = 5.21; 95% CI, 1.15-23.57; P =. 032) were independent risk factors for fracture in recipients of KT. Pretransplant osteoporosis and osteopenia were independent risk factors for fracture after KT. More careful monitoring of bone mineral density before and after KT might be beneficial to predict the risk for fracture after KT. • Twenty out of 941 patients had fractures in the Korean cohort study for Outcome in Patients With Kidney Transplantation. • Pretransplant osteoporosis and osteopenia were risk factors for fracture in kidney transplantation. • Mineral and bone biochemical marker changes were not related to fracture. [ABSTRACT FROM AUTHOR]

Compared to tacrolimus, cyclosporine increases cardiovascular risk. Furthermore, tacrolimus has a negative effect on glucose metabolism compared to cyclosporine. This study investigated the effect of the conversion from cyclosporine to tacrolimus for immunosuppressive therapy on glucose metabolism and cardiovascular risk profiles in long-term stable kidney transplant recipients (KTRs). In this prospective, open-label, single-arm study, 36 KTRs were enrolled; 3 were excluded. Patients were evaluated for glucose metabolism and cardiovascular risk factors at baseline, 3, and 6 months after conversion of medication. Serial changes were analyzed by repeated analysis of variance. The mean duration from transplantation was 12.6 ± 4.0 years and baseline serum creatinine levels were 1.10 ±.23 mg/dL. After conversion, fasting plasma glucose levels increased sequentially from 101.7 ± 18.5 to 107.4 ± 21.3 mg/dL (P =. 007), and glycated hemoglobin levels increased from 5.7 ±.8 to 6.0 ± 1.2% (P =. 016). Among cardiovascular risk factors, fibrinogen levels were decreased (P =. 015), but other factors, including blood pressure and lipid profile, did not change (all P >. 05). There was no change in renal function, including serum creatinine (P =. 611) and urine protein-to-creatinine ratio (P =. 092). Body mass index levels were decreased (P =. 037) and body weight tended to decrease (P =. 063). Switching immunosuppressant therapy to tacrolimus has an apparent negative effect on glucose metabolism and imparts an unclear advantage on cardiovascular risk profiles for long-term stable KTRs. • The conversion effect of calcineurin inhibitors in long-term stable KTRs was prospectively evaluated. • Conversion cyclosporine to tacrolimus was detrimental for glucose metabolism. • No clear benefits on cardiovascular risk profiles and graft function. [ABSTRACT FROM AUTHOR]

α 1 -Antitrypsin (AAT) is an important protein in the anti-inflammatory response that functions to regulate the activity of serine proteinases. We aimed to evaluate the protective effect of AAT on ischemia-reperfusion injury (IRI) in a mouse model. We investigated the effects of AAT in a C57BL/6 mouse model of IRI by dividing them into 4 groups: normal control, sham operated, ischemia-reperfusion (IR), and IR after AAT pretreatment (IR-AAT). In the IR-AAT group, mice were pretreated with AAT (80 mg/kg/d) for 3 days before renal ischemia was induced by clamping the bilateral renal vascular pedicles for 30 minutes. At 24 hours after IRI, biochemistry, histology, inflammatory cytokines, and apoptosis were assayed. Blood urea nitrogen and serum creatinine levels were significantly lower in the IR-AAT group than in the IR group. Neutrophil gelatinase-associated lipocalin and kidney injury molecule 1 protein levels were significantly lower in the IR-AAT group than in the IR group. In addition, there were fewer tubular injuries and less interstitial fibrosis in the IR-AAT group than in the IR group, and the expression levels of transforming growth factor β, interleukin 1β, and interleukin 6 were significantly lower in the IR-AAT group than in the IR group. When compared with the IR group, there were fewer terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay–positive cells, lower caspase 3 activity and B-cell lymphoma 2-associated X protein (Bax), and higher B-cell lymphoma 2 (Bcl–2) in the IR-AAT group. α 1 -Antitrypsin preserved renal function, attenuated tubular injuries and interstitial fibrosis, and inhibited inflammation and apoptosis after renal IRI. Our results suggest that AAT has protective effects against renal IRI by inhibiting inflammatory and apoptosis pathways. • α 1 -Antitrypsin (AAT) is an important protein in the anti-inflammatory response that functions to regulate the activity of serine proteinases. • Treatment with AAT before renal ischemia-reperfusion injury (IRI) reduced IRI, as shown by the significantly lower levels of blood urea nitrogen, serum creatinine, • Neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and fewer tubular injuries and interstitial fibrosis were in the AAT pretreatment group compared with the ischemia-reperfusion group. • With respect to the mechanisms underlying the protective effect of AAT against renal IRI, administration of AAT before renal IRI decreased inflammation, as demonstrated by the reduced expression of transforming growth factor β, interleukin 1β, and interleukin 6. • In addition, apoptosis, as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, caspase 3 activity, and the expression of B-cell leukemia/lymphoma 2-associated X protein, was inhibited by AAT pretreatment. • Based on these results, AAT protects against ischemia reperfusion–induced kidney damage through anti-inflammatory and antiapoptotic pathways. [ABSTRACT FROM AUTHOR]

Introduction: HLA-incompatible (HLAi) and ABO-incompatible (ABOi) kidney transplantation (KT) has been on the increase over the last decade. However, there are wide variations in outcomes from these procedures. In this study we evaluated the graft and patient outcomes in incompatible KT and non-sensitized KT. Methods: Patients who underwent KT between January 2012 and April 2018 were enrolled and reviewed. We divided kidney transplant recipients (KTRs) into five groups as follows: HLAi (n = 50); ABOi (n = 65); HLAi+ABOi (n = 5); control (n = 428); and living-donor control (LD control, n = 218). We compared the risk of rejection, graft function, graft survival, and patient survival between incompatible KTRs and control/LD control KTRs. Results: Although the incidence of active antibody-mediated rejection in HLAi group tends to be higher than in control and LD control groups (6.0% vs. 2.8%, P = 0.20; 6.0% vs. 3.7%, P = 0.44, respectively), the rejection-free survival, graft survival, and patient survival were not significantly different from those of the control and LD control groups in all three incompatible KT groups (all P>0.05). Graft function during the study period was also not different between incompatible KTRs and control/LD control groups (both P>0.05). Using Cox regression analysis, neither HLAi nor ABOi were risk factors for graft failure. Some infectious diseases such as urinary tract infection and cytomegalovirus infection were more common in the HLAi group than in the control/LD control group (both P<0.05), but only one infection-related death occurred in HLAi KTRs. Infection risks were similar in the ABOi and HLAi+ABOi groups compared to controls. Conclusion: Our results showed favorable outcomes for incompatible KT after desensitization. Although desensitization therapy for incompatible KT has improved access to transplantation for KT candidates with high immunological risk, more clinical data are clearly needed. [ABSTRACT FROM AUTHOR]

Background Increasing prevalence of mupirocin-resistant Staphylococcus aureus have been reported, and chlorhexidine resistance has become an issue. This study aimed to investigate the prevalence of mupirocin and chlorhexidine resistance in both colonized and infection causing Staphylococcus aureus in children, and find factors associated with increased virulence. Methods S taphylococcus aureus, isolated from children <18 years old admitted at a single center, were collected prospectively from August 2017 to July 2018. The isolates underwent multilocus sequence typing and were screened for genes causing chlorhexidine resistance (qac A/B), quaternary ammonium resistance (smr), mupirocin resistance (ileS mutation, Mup A, Mup B), and Pantone Valentine Leucocidin (pvl) toxin. Results During the study period, a total of 49 non-duplicate isolates were included, of which 69.4% (n = 34) were Methicillin-resistant Staphylococcus aureus (MRSA). Of the colonizers (n = 25), the most common sequence type was ST 72 (68.0%), whereas among pathogens (n = 24), ST 72 (29.2%) and ST 89 (29.2%) were most prevalent. Pathogens in this study caused abscess formation (n = 3), sepsis (n = 4), and skin infections such as cellulitis and omphalitis (n = 17). Mupirocin resistance was found in 16.0% among colonizers vs. 45.8% among pathogens (P = 0.023). High-level mupirocin resistance was more common (n = 3/25, 12.0%) than low-level mupirocin resistance (n = 1/25, 4.0%) in colonizers, whereas, pathogens had similar rates of low-level (25.0%) and high-level (n = 20.8%) mupirocin resistance. PVL toxin gene was more frequently found in colonizers than pathogens (64.0% vs. 33.3%, P = 0.032), and all isolates had quaternary ammonium resistance genes. Chlorhexidine resistance gene was found in only 3 MRSA isolates colonized in the nares of preterm infants. All were SCCmec type 4, however, two were ST 72, spa type t1054, which had high -level mupirocin resistance and PVL toxin gene. Conclusion A PVL toxin gene-positive MRSA which had genes causing mupirocin and chlorhexidine resistance were found in the nasal carriages of preterm infants. These stains may cause failure of MRSA eradication in hospital settings, using conventional methods of nasal mupirocin application and chlorhexidine bathing. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background: Acute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary exosomes of KTRs. Methods: Among 458 graft biopsies enrolled in a cross-sectional multicenter study, 22 patients with stable graft function (STA) who had not shown pathologic abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We performed proteomic analysis using nano-ultra performance liquid chromatography-tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for early TCMR diagnosis on urinary exosomes. We confirmed the protein levels of each candidate biomarker by western blot analysis. Results: A total of 169 urinary exosome proteins were identified by nano-UPLC-MS/MS. Forty-six proteins showed increased expression in STA patients, while 17 proteins were increased in TCMR patients. Among them, we selected five proteins as candidate biomarkers for early diagnosis of TCMR according to significance, degree of quantity variance, and information from the ExoCarta database. We confirmed the proteomic expression levels of five candidate biomarkers by western blot analysis in each patient. Of all candidate biomarkers, tetraspanin-1 and hemopexin were significantly higher in TCMR patients (STA:TCMR ratio = 1:1.8, P = 0.009, and 1:3.5, P = 0.046, respectively). Conclusions: Tetraspanin-1 and hemopexin were detected in KTR urine and could act as potential diagnostic proteins for TCMR. [ABSTRACT FROM AUTHOR]

This study assessed the seismic vulnerability of reinforced concrete columns jacketed by fiber-reinforced polymer (FRP) wires. To achieve this goal, four column specimens subjected to cyclic load tests were selected to validate the analytical model of existing and FRP retrofitted columns in OpenSees; the specimens included two existing columns with lap-spliced and continuous longitudinal reinforcement and two FRP wire-jacketed columns with lap-spliced and continuous longitudinal reinforcement. Two types of material models (‘Concrete’ versus ‘Pinching’) were used to simulate the concrete material models of columns. Based on the validation results, the advantages and disadvantages of using of two material models were considered. Additionally, to compare the seismic performance of the columns subjected to ground motions, their fragility curves were developed. Comparison results revealed that the retrofitting effect using the ‘Pinching’ model is superior, but use of the ‘Concrete’ model is also acceptable. However, the ‘Pinching’ model is more vulnerable than the ‘Concrete’ model for specimens exhibiting limited ductility. [ABSTRACT FROM AUTHOR]

Background: The incidence of many chronic diseases is increasing rapidly in South Korea. Rheumatoid arthritis is a chronic disease for which treatment by both doctors and long-term self-care by patients is deemed very important for successful disease management. Purpose: This study is designed to examine and identify the factors influencing self-care competence in Korean women with rheumatoid arthritis. Methods: A cross-sectional descriptive design was employed. Participants included 132 women aged 20 years or older who were visiting rheumatoid arthritis outpatient clinics at hospitals in Seoul and Gyeonggi-do, South Korea. Measures included a demographics form, Self-as-Carer Inventory, Korean Activities of Daily Living scale, Visual Analogue Scale, Mishel Uncertainty in Illness Scale–Community Form, and Self-esteem Scale. Results: The analyses illustrated the significance of the prediction model (F = 21.744, p <.001). The value of the adjusted R 2 was set at.401, corresponding to 40.1% explanatory power. Uncertainty (β = −.43) and self-esteem (β =.26) were identified as having the most influence on self-care competence in Korean women with rheumatoid arthritis. Conclusions/Implications for Practice: This cross-sectional study yielded preliminary evidence that nursing interventions that reduce uncertainty and improve self-esteem in Korean women with rheumatoid arthritis are necessary to promote the self-care competence of this vulnerable population. Healthcare professionals should recognize uncertainty and self-esteem as factors that influence self-care competence in Korean women with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background: The incidence of many chronic diseases is increasing rapidly in South Korea. Rheumatoid arthritis is a chronic disease for which treatment by both doctors and long-term self-care by patients is deemed very important for successful disease management. Purpose: This study is designed to examine and identify the factors influencing self-care competence in Korean women with rheumatoid arthritis. Methods: A cross-sectional descriptive design was employed. Participants included 132 women aged 20 years or older who were visiting rheumatoid arthritis outpatient clinics at hospitals in Seoul and Gyeonggi-do, South Korea. Measures included a demographics form, Self-as-Carer Inventory, Korean Activities of Daily Living scale, Visual Analogue Scale, Mishel Uncertainty in Illness Scale–Community Form, and Self-esteem Scale. Results: The analyses illustrated the significance of the prediction model (F = 21.744, p <.001). The value of the adjusted R 2 was set at.401, corresponding to 40.1% explanatory power. Uncertainty (β = −.43) and self-esteem (β =.26) were identified as having the most influence on self-care competence in Korean women with rheumatoid arthritis. Conclusions/Implications for Practice: This cross-sectional study yielded preliminary evidence that nursing interventions that reduce uncertainty and improve self-esteem in Korean women with rheumatoid arthritis are necessary to promote the self-care competence of this vulnerable population. Healthcare professionals should recognize uncertainty and self-esteem as factors that influence self-care competence in Korean women with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background: The association of a higher body mass index (BMI) with better survival is a well-known “obesity paradox” in patients on hemodialysis (HD). However, men and women have different body compositions, which could impact the effect of BMI on mortality. We investigated the effect of gender on the obesity-mortality relationship in Korean patients on HD. Methods: This study included 2,833 maintenance patients on HD from a multicenter prospective cohort study in Korea (NCT00931970). The relationship between categorized BMI and gender-specific mortality was evaluated by an adjusted Cox proportional hazard model with restricted cubic spline analyses and the Competing risk analysis. We also investigated the effect of changes in BMI over 12 months and serum creatinine level on survival in male and female patients on HD. Results: The mean BMI was 22.6 ± 3.3 kg/m2 and the mean follow up duration was 24.2 ± 3.4 months. The patients with the highest quintile of BMI (≥25.1 kg/m2) showed lower mortality (subdistributional hazard ratio [SHR] = 0.63, 95% confidence interval [CI] = 0.43–0.93, P = 0.019) compared with those with the reference BMI quintile. When analyzed by gender, male patients with a BMI over 25.1 kg/m2 had lower mortality risk (HR = 0.43, 95% CI = 0.25–0.75, P = 0.003); however, no significant difference was found in female patients. Increased BMI after 12 months and high serum creatinine were associated with better survival only in male patients on HD. Conclusions: BMI could be used as a risk factor for mortality in male patients on HD. However, the mortality of female patients on HD was not related with baseline and follow-up BMI. This suggests that BMI is a good surrogate marker of lean body composition, especially in male patients on HD. [ABSTRACT FROM AUTHOR]

Prevalent anuric peritoneal dialysis (PD) patients usually have higher mortality than PD patients with residual urine volume. We aimed to evaluate the predictors of survival in anuric PD patients. Anuric PD patients (n = 505, <100 mL of daily urine) enrolled in Korean nationwide prospective cohort were analyzed. Survived and non-survived anuric PD patients were compared by propensity score matching analysis with a ratio of two to one. The propensity method was used to adjust for patient age, dialysis duration, and presence of diabetes. Among the total anuric PD patients, non-survived patients showed a significantly older age, higher incidence of diabetes, coronary artery disease, and arrhythmia, and lower serum creatinine and albumin. After propensity score matching, multivariate Cox regression analysis for patient survival showed a decreasing risk as serum albumin increased (HR = 0.347, p = 0.0094). Analysis using the receiver-operating-characteristic (ROC) curve showed that survival could be predicted with a sensitivity of 59.4% and a specificity of 63.2% using a cutoff value of 3.6 g/dL of serum albumin in unmatched total PD patients. The beneficial impact of high albumin level on death was significantly greater for patients with older age (≥50 years), no diabetes, low ultrafiltration (UF) volume (<1000 mL/day), and low levels of serum creatinine (<10 mg/dL), total cholesterol (<177.5 mg/dL), ferritin (<100 ng/mL), and high-sensitivity C-reactive protein (hs-CRP) (<0.1 mg/dL). Survival in anuric PD patients was associated with age, comorbidities, and nutritional factors such as creatinine and albumin. After adjustment by propensity score matching, serum albumin level was an independent predictor for survival in anuric PD patients. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate whether the combination of inflammatory markers could provide predictive powers for mortality in individual patients on dialysis and develop a predictive model for mortality according to dialysis modality. Data for inflammatory markers were obtained at the time of enrollment from 3,309 patients on dialysis from a prospective multicenter cohort. Net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated. Cox proportional hazards regression analysis was used to derive a prediction model of mortality and the integrated area under the curve (iAUC) was calculated to compare the predictive accuracy of the models. The incremental additions of albumin, high-sensitive C-reactive protein (hsCRP), white blood count (WBC), and ferritin to the conventional risk factors showed the highest predictive powers for all-cause mortality in the entire population (NRI, 21.0; IDI, 0.045) and patients on peritoneal dialysis (NRI, 25.7; IDI, 0.061). The addition of albumin and hsCRP to the conventional risk factors markedly increased predictive powers for all-cause mortality in HD patients (NRI, 19.0; IDI, 0.035). The prediction model for all-cause mortality using conventional risk factors and combination of inflammatory markers with highest NRI value (iAUC, 0.741; 95% CI, 0.722–0.761) was the most accurate in the entire population compared with a model including conventional risk factors alone (iAUC, 0.719; 95% CI, 0.700–0.738) or model including only significant conventional risk factors and inflammatory markers (iAUC, 0.734; 95% CI, 0.714–0.754). Using multiple inflammatory markers practically available in a clinic can provide higher predictive power for all-cause mortality in patients on dialysis. The predictive model for mortality based on combinations of inflammatory markers enables a stratified risk assessment. However, the optimal combination for the predictive model was different in each dialysis modality. [ABSTRACT FROM AUTHOR]

Aims: The long‐term safety and efficacy of gemigliptin was evaluated in the present extension study after a 12‐week study during a 40‐week follow‐up period. Methods: The main study was a randomized, placebo‐controlled, double‐blinded, phase IIIb study in which 50 mg of gemigliptin (N = 66) or placebo (N = 66) was administered to patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment over a 12‐week period. Patients with a glycated haemoglobin (HbA1c) level of 7% to 11% and an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m2 were enrolled in the main study. After 12 weeks, patients in the gemigliptin group continued to receive gemigliptin (N = 50), whereas patients in the placebo group were transitioned from placebo to linagliptin (N = 52). Each group received the indicated treatment over the subsequent 40‐week period. A total of 102 patients consented to participate in the extension study, and 79 patients ultimately completed the study. Results: The HbA1c levels of both groups were significantly reduced at week 52 compared with baseline. Specifically, the adjusted mean change ± standard error in HbA1c level in the gemigliptin and placebo/linagliptin groups was 1.00% ± 0.21% and 0.65% ± 0.22% lower at week 52 than at baseline (P < .001 and P = .003), respectively. No significant difference in the change in HbA1c level was found between the 2 groups (P = .148). Trends in fasting plasma glucose, fructosamine and glycated albumin levels in the 2 groups were similar to trends in HbA1c levels. The eGFR of both groups was also significantly lower at week 52 than at baseline, and no significant difference in change in eGFR was found between the 2 groups. In contrast, both drugs had little effect on urinary albumin excretion, although both drugs significantly reduced the urinary type IV collagen level. The overall rates of adverse events were similar between the 2 groups. Conclusions: Gemigliptin and linagliptin did not differ with respect to safety and efficacy in patients with T2DM and renal impairment. The 2 drugs had similar glucose‐lowering effects, and the changes in eGFR and albuminuria were also similar. Additionally, the risk of side effects, including hypoglycaemia, was similar between the 2 groups. [ABSTRACT FROM AUTHOR]

Contrast-induced acute kidney injury (CIAKI) is a leading cause of acute kidney injury following radiographic procedures. Intrarenal oxidative stress plays a critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidases (Noxs) are important sources of reactive oxygen species (ROS). Among the various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents. Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using in vivo and in vitro models. HK-2 cells were treated with iohexol, with or without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831). Effects of Nox4 inhibition on CIAKI mice were examined. Expression of Nox4 in HK-2 cells was significantly increased following iohexol exposure. Silencing of Nox4 rescued the production of ROS, downregulated pro-inflammatory markers (particularly phospho-p38) implicated in CIAKI, and reduced Bax and caspase 3/7 activity, which resulted in increased cellular survival in iohexol-treated HK-2 cells. Pretreatment with GKT137831 replicated these effects by decreasing levels of phospho-p38. In a CIAKI mouse model, even though the improvement of plasma blood urea nitrogen was unclear, pretreatment with GKT137831 resulted in preserved structure, reduced expression of 8-hydroxy-2’-deoxyguanosine (8OHdG) and kidney injury molecule-1 (KIM-1), and reduced number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive cells. These results suggest Nox4 as a key source of reactive oxygen species responsible for CIAKI and provide a novel potential option for prevention of CIAKI. [ABSTRACT FROM AUTHOR]

Purpose Sevelamer, a noncalcium phosphate binder, has been shown to attenuate the progression of vascular calcification and improve survival in patients with chronic kidney disease undergoing dialysis compared with calcium-based binders. Using real-world data from a cohort study and the Health Insurance Review and Assessment Service database, we conducted a cost-effectiveness analysis comparing sevelamer with calcium acetate in dialysis patients from the perspective of the National Health Insurance Service in South Korea. Methods Data (demographic, diagnostic, laboratory, and survival) from 4674 patients undergoing dialysis enrolled in a multicenter prospective cohort study conducted in South Korea between September 2008 and December 2012 were linked to phosphate binder use, hospitalization, and cost data available from the Health Insurance Review and Assessment Service database. After propensity score matching, a dataset comprising comparable patients treated with either sevelamer (n = 501) or calcium acetate (n = 501) was used in the cost-effectiveness analysis. A Markov model was used to estimate costs, life years, quality-adjusted life years (QALYs), and cost-effectiveness over each patient’s lifetime. Forty-month treatment-specific overall survival (OS) data available from the dataset were extrapolated to lifetime survival with the use of regression analysis. Findings Patients had a mean age of 56.3 years and were treated with dialysis for a mean duration of 67.6 months. Compared with calcium acetate, sevelamer was associated with an incremental cost of South Korean Won (₩) 12,246,911 ($10,819) and a gain of 1.758 life years and 1.108 QALYs per patient. This outcome yielded incremental cost-effectiveness ratios of ₩6,966,350 ($6154) and ₩11,057,699 ($9768) per life year and QALY gained, respectively. Conclusions regarding sevelamer’s cost-effectiveness were insensitive to alternative assumptions in time horizon, discount rate, hospitalization rate, costs, and health utility estimates, and they remained consistent in 100% of the model iterations, considering a willingness-to-pay threshold of ₩31,894,720 ($28,176) per QALY gained. Implications This analysis of real-world data found that sevelamer’s higher cost relative to calcium acetate was adequately offset by improved survival among patients undergoing dialysis in South Korea. As such, sevelamer offers good value for money, representing a cost-effective alternative to calcium-based binders. [ABSTRACT FROM AUTHOR]

Background: Immunosuppression non-adherence in kidney transplant recipients (KTRs) not only increases the risk of medical intervention due to acute rejection and graft loss but burdens the socioeconomic system in the form of increased healthcare costs. An aggressive preemptive effort by healthcare professionals, geared to ensure adherence to immunosuppressants in KTRs, is significant and imperative.Methods/design: This study was designed as a prospective, open-label, multicenter, randomized controlled study aimed at evaluating the efficacy and stability of an information and communication technology (ICT)-based centralized monitoring system in boosting medication adherence in KTRs. One hundred fourteen KTRs registered throughout the year 2017 to 2018 are randomized into either the ICT-based centralized home monitoring system or to ambulatory follow-up. The planned follow-up duration is 6 months. The ICT-based centralized home monitoring system described consists of a smart pill box equipped with personal identification system, a home monitoring system, an electronic Case Report Form (eCRF) system, and a comprehensive clinical trial management system (CTMS). It alerts both patients and medical staff with texts and pill box alarms if there is a dosage/dosing time error or a missed dose. Medication adherence and transplant outcomes for the follow-up period are compared between the two groups, while patient satisfaction as well as the stability and cost-effectiveness of the ICT-based monitoring system are to be evaluated.Discussion: This on-going study is expected to determine if consistent use of the ICT-based centralized monitoring system described could maximize mediation adherence and subsequently enhance transplant outcomes in KTRs. Further, it would lay the foundation for successful implementation of this ICT-based monitoring system for effective management of medication adherence in KTRs.Trials Registration: ClinicalTrials.gov, Identifier: NCT03136588 . Registered on 20 April 2017. [ABSTRACT FROM AUTHOR]

Background: The role of mineral metabolism in mortality among dialysis patients has received increased attention, but some aspects remain unclear. The aim of the present study was to investigate the prognostic value of serum calcium and phosphate levels for all-cause mortality and cause-specific mortality in dialysis patients. Methods: Patients on hemodialysis and peritoneal dialysis were enrolled from a multicenter prospective cohort study in Korea (NCT00931970). The patients were divided into low, normal, and high groups according to their baseline serum calcium or phosphate levels. Cox proportional analysis and a proportional hazards model for the subdistribution of a competing risk were used to calculate hazard ratios (HRs) for the association of serum calcium and phosphate levels with all-cause and cause-specific mortality. Time-dependent values of calcium and phosphate were also evaluated to assess the effect of longitudinal change in mineral metabolism parameters on mortality types. Results: A total of 3,226 dialysis patients were followed up for a mean of 19.8 ± 8.2 months. Infection was the most common cause of death. Low serum phosphate was significantly associated with all-cause and infection-related death using time-dependent values (HR, 1.43 [95% confidence interval (CI), 1.06–1.93], P = 0.02, and HR, 1.66 [95% CI, 1.02–2.70], P = 0.04, respectively). Low serum phosphate was associated with significantly higher infection-related mortality, especially in patients older than 65 years or on dialysis more than one year or with serum albumin lower than 3.9 g/dL (HR, 2.06 [95% CI, 1.13–3.75], P = 0.02, HR, 2.19 [95% CI, 1.20–4.01], P = 0.01, and HR, 1.77 [95% CI, 1.00–3.13], P = 0.05, respectively). Multinomial logistic regression analysis results suggested that low serum albumin, creatinine, and body mass index correlated with low serum phosphate. Conclusions: Low serum phosphate in dialysis patients was an independent risk factor for infection-related death, especially in elderly patients. Persistently low serum phosphate might be a nutritional biomarker to predict increased susceptibility to infection and in turn worse outcomes in dialysis patients. [ABSTRACT FROM AUTHOR]

Although dipeptidyl peptidase-4 inhibitors, a class of antidiabetic drugs, have various pleiotropic effects, it remains undetermined whether gemigliptin has a beneficial effect on vascular calcification. Therefore, this study was performed to evaluate the effect of gemigliptin on vascular calcification in a rat model of adenine-induced chronic kidney disease and in cultured vascular smooth muscle cells. Gemigliptin attenuated calcification of abdominal aorta and expression of RUNX2 in adenine-induced chronic kidney disease rats. In cultured vascular smooth muscle cells, phosphate-induced increase in calcium content was reduced by gemigliptin. Gemigliptin reduced phosphate-induced PiT-1 mRNA expression, reactive oxygen species generation, and NADPH oxidase mRNA expression (p22phox and NOX4). The reduction of oxidative stress by gemigliptin was associated with the downregulation of phospho-PI3K/AKT expression. High phosphate increased the expression of frizzled-3 (FDZ3) and decreased the expression of dickkopf-related protein-1 (DKK-1) in the Wnt pathway. These changes were attenuated by gemigliptin treatment. Gemigliptin restored the decreased expression of vascular smooth muscle cells markers (α-SMA and SM22α) and increased expression of osteogenic makers (CBFA1, OSX, E11, and SOST) induced by phosphate. In conclusion, gemigliptin attenuated vascular calcification and osteogenic trans-differentiation in vascular smooth muscle cells via multiple steps including downregulation of PiT-1 expression and suppression of reactive oxygen species generation, phospho-PI3K/AKT, and the Wnt signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The risk of developing tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is expected to be relatively high in an intermediate TB burden country. This single-center retrospective study was conducted to investigate risk factors and the incidence of TB after allogeneic HSCT. Methods: From January 2004 to March 2011, 845 adult patients were enrolled. Starting April 2009, patients were given isoniazid (INH) prophylaxis based on interferon-γ release assay results. The incidence of TB was analyzed before and after April 2009, and compared it with that of the general population in Korea. Results: TB was diagnosed in 21 (2.49%) of the 845 allogeneic HSCT patients. The median time to the development of TB was 386 days after transplantation (range, 49–886). Compared with the general population, the standardized incidence ratio of TB was 9.10 (95% CI; 5.59–14.79). Extensive chronic graft-versus-host disease (GVHD) was associated with the development of TB (P = 0.003). Acute GVHD, conditioning regimen with total body irradiation and conditioning intensity were not significantly related. INH prophylaxis did not reduce the incidence of TB (P = 0.548). Among 21 TB patients, one patient had INH prophylaxis. Conclusion: Allogeneic HSCT recipients especially those who suffer from extensive chronic GVHD are at a high risk of developing TB. INH prophylaxis did not statistically change the incidence of TB, however, further well-designed prospective studies are needed. [ABSTRACT FROM AUTHOR]

Endothelial cell injury and dysfunction caused by reactive oxygen species (ROS) are implicated in the pathogenesis of vascular diseases. ROS are generated and hypoxanthine is degraded by xanthine oxidase. Smoking and alcohol consumption are associated with an increased level of hypoxanthine. We aimed to study the direct role of hypoxanthine in endothelial dysfunction in human umbilical vascular endothelial cells (HUVECs). Hypoxanthine induced cell death and production of ROS. Furthermore, hypoxanthine induced apoptosis through regulation of protein expression related to apoptosis. When cells were pretreated with N -acetylcysteine or a pancaspase inhibitor (Z-VAD-fmk) and stimulated with hypoxanthine, Z-VAD-fmk and N -acetylcysteine prevented hypoxanthine-induced apoptosis by inhibiting the ROS production and caspase pathway. Thus, an increased extracellular concentration of hypoxanthine induces endothelial dysfunction through ROS production and regulates expression of apoptosis-related proteins in HUVECs. These effects are expected to be associated with some vascular diseases. [ABSTRACT FROM AUTHOR]

Nonislet cell tumor hypoglycemia (NICTH) is a rare but serious paraneoplastic syndrome in which a tumor secretes incompletely processed precursors of insulin-like growth factor-II (IGF-II), causing hypoglycemia. Here, we report an exceptional case of NICTH caused by nonfunctioning adrenocortical carcinoma in a 39-year-old male with recurrent hypoglycemia. The patient’s serum IGF-II/IGF-I ratio had increased to 27.8. The serum level of the IGF-II/IGF-I ratio was normalized after removal of the tumor, and the hypoglycemic attacks no longer occurred after the operation. [ABSTRACT FROM AUTHOR]

Because of concerns about accumulation of cyclodextrin, oral voriconazole is recommended for patients with renal impairment. However, intravenous voriconazole may occasionally be imperative in critically ill patients with life-threatening invasive aspergillosis. We investigated the clinical effects of intravenous voriconazole formulated with sulfobutylether β-cyclodextrin ( SBECD) in patients with renal impairment. A prospective observational study was conducted on 25 adult patients with haematological malignancies who were treated with intravenous voriconazole for invasive aspergillosis. Among them, seven patients had a baseline creatinine clearance (CrCl) <50 ml min−1 (case). Although voriconazole trough concentrations were significantly higher in cases (5.84 mg l−1) than controls (2.28 mg l−1), the proportion of concentrations within the target range did not differ between two groups (4/7 and 12/18, respectively; P = 0.658). The frequency of severe adverse events in cases (3/7) was comparable to that of controls (4/18; P = 0.355). No patients showed significant deterioration in renal function after the voriconazole therapy even in patients with renal impairment. Although CrCl <50 ml min−1 was associated with higher voriconazole concentrations, its clinical impact remains unclear. SBECD-formulated intravenous voriconazole did not lead to a higher incidence of severe adverse events including nephrotoxicity in haematological patients with CrCl <50 ml min−1. [ABSTRACT FROM AUTHOR]

Alpha1-antitrypsin (AAT) exerts its anti-inflammatory effect through regulating the activity of serine proteinases. This study evaluated the inhibitory effects of AAT against the transforming growth factor (TGF)-β1 induced epithelial-to-mesenchymal transition (EMT) in unilateral ureter obstruction (UUO) mice and Madin-Darby canine kidney (MDCK) cells. C57BL/6 mice with induced UUO were injected intraperitoneally with AAT (80 mg/Kg) or vehicle for 7 days. MDCK cells were treated with TGF-β1 (2 ng/mL) for 48 hours to induce EMT, and co-treated with AAT (10 mg/mL) to inhibit the EMT. Masson’s trichrome and Sirius red staining was used to estimate the extent of renal fibrosis in UUO mice. The expression of alpha-smooth muscle actin (α-SMA), vimentin, fibronectin, collagen I, and E-cadherin in MDCK cells and kidney tissue were evaluated. Masson’s and Sirius red staining revealed that the area of renal fibrosis was significantly smaller in AAT treated UUO group compared with that of UUO and vehicle treated UUO groups. AAT treatment attenuated upregulation of Smad2/3 phosphorylation in UUO mouse model. Co-treatment of MDCK cells with TGF-β1 and AAT significantly attenuated the changes in the expression of α-SMA, vimentin, fibronectin, collagen I, and E-cadherin. AAT also decreased the phosphorylated Smad3 expression and the phosphorylated Smad3/Smad3 ratio in MDCK cells. AAT treatment inhibited EMT induced by TGF-β1 in MDCK cells and attenuated renal fibrosis in the UUO mouse model. The results of this work suggest that AAT could inhibit the process of EMT through the suppression of TGF-β/Smad3 signaling. [ABSTRACT FROM AUTHOR]

BackgroundTherapeutic drug monitoring of mycophenolic acid (MPA) is required to optimize the immunosuppressive effect and minimize toxicity. We validated a new particle-enhanced turbidimetric inhibition immunoassay (PETINIA) for the determination of MPA levels and evaluated the relationship of MPA trough level with drug-related adverse events.MethodsPETENIA and liquid chromatography-mass spectrometry (LC-MS) were used to determine MPA concentrations from 54 kidney transplant recipients (KTRs). Agreement between PETINIA and LC-MS results was assessed by Passing-Bablok regression and the Bland-Altman plot method. The association of adverse events with MPA trough level obtained by PETINIA was analyzed.ResultsPETINIA revealed a good agreement with the LC-MS; Regression analysis gave an equation of y = 1.27x − 0.12 (r2 = 0.975,p < 0.001). PETINIA showed a systemic positive bias with a mean difference of 0.66 mg/L compared to LC-MS. However, the magnitude of the positive bias decreased to 0.44 mg/L within the therapeutic range of MPA. Multiple logistic regression showed that MPA trough level determined by PETINIA was an independent risk factor for adverse events (odds ratio 2.28, 95% CI 1.25–4.16,p = 0.007). MPA trough level predicted adverse events with a sensitivity of 77.8% and a specificity of 86.7% using a cut-off level of 5.25 mg/L.ConclusionsGood correlation between the two methods indicates that PETINIA is an acceptable method for the monitoring of MPA therapeutic levels. Furthermore, MPA trough level obtained by PETINIA is a useful monitoring tool to minimize toxicity in KTRs. [ABSTRACT FROM PUBLISHER]

Ethnopharmacological relevance Acorus gramineus rhizoma ( AGR) is the dry rhizome of Acorus gramineus Solander from the family Araceae that has been used as sedative, analgesic, diuretic, digestive and antifungal agent. Aim of the study To evaluate the no-observed-adverse-effect level (NOAEL) and the toxicity of AGR, following repeated oral administration to rats for 13 weeks. Materials and methods AGR was administered by oral gavage to groups of rats (10 per group, each sex) at doses of 0 (control), 25, 74, 222, 667, or 2,000 mg/kg/day, 5 times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology, sperm motility, sperm morphology, organ weights, gross and histopathological findings were compared between control and AGR groups. Results No mortality or remarkable clinical signs were observed during this 13-week study. No adverse effects on body weight, food consumption, urinalysis, hematology, serum chemistry, organ weights, gross lesion, histopathology, vaginal cytology, sperm motility or deformity were observed in any of the male or female rats treated with AGR. Conclusions On the basis of these results, the NOAEL of AGR is determined to be 2,000 mg/kg/day for male and female rats. [ABSTRACT FROM AUTHOR]