Single-Center Experience Using Marginal Liver Grafts in Korea.

BACKGROUND: Liver transplantation (LT) is an established therapeutic modality for patients with end-stage liver disease. The use of marginal donors has become more common worldwide due to the sharp increase in recipients, with a consequent shortage of suitable organs. We analyzed our single-center experience over the last 8 years in LT to evaluate the outcomes of using so-called "marginal donors." METHODS: We retrospectively analyzed the database of all LTs performed at our institution from 2009 to 2017. Only patients undergoing deceased-donor LTs were analyzed. Marginal grafts were defined as livers from donors >60 years of age, livers from donors with serum sodium levels >155 mEq, graft steatosis >30%, livers with cold ischemia time ≥12 hours, livers from donors who were hepatitis B or C virus positive, livers recovered from donation after cardiac death, and livers split between 2 recipients. Patients receiving marginal grafts (marginal group) were compared with patients receiving standard grafts (standard group). RESULTS: A total of 106 patients underwent deceased-donor LT. There were 55 patients in the standard group and 51 patients in the marginal group. There were no significant differences in terms of age, sex, Model for End-Stage Liver Disease score, underlying liver disease, presence of hepatocellular carcinoma, and hospital stay between the 2 groups. Although the incidence of acute cellular rejection, cytomegalovirus infection, and postoperative complications was similar between the 2 groups, the incidence of early allograft dysfunction was higher in the marginal group. With a median follow-up of 26 months, the 1-, 3-, and 5-year overall and graft (death-censored) survivals in the marginal group were 85.5%, 75%, and 69.2% and 85.9%, 83.6%, and 77.2%, respectively. Patient overall survival and graft survival (death-censored) were significantly lower in the marginal group (P = .023 and P = .048, respectively). On multivariate analysis, receiving a marginal graft (hazard ratio [HR], 4.862 [95% confidence interval (CI), 1.233-19.171]; P = .024) and occurrence of postoperative complications (HR, 4.547 [95% CI, 1.279-16.168]; P = .019) were significantly associated with worse patient overall survival. Also, when factors associated with marginal graft were analyzed separately, graft steatosis >30% was independently associated with survival (HR, 5.947 [95% CI, 1.481-23.886]; P = .012). CONCLUSIONS: Patients receiving marginal grafts showed lower but acceptable overall survival and graft survival. However, because graft steatosis >30% was independently associated with worse survival, caution must be exercised when using this type of marginal graft by weighing the risk and benefits.

Highly Dispersible Buckled Nanospring Carbon Nanotubes for Polymer Nano Composites.

We propose the unique structure of highly dispersible single-walled carbon nanotubes (SWCNTs) in various solvents and polymers using the ZnO nano particle template. Buckled nanospring-shaped carbon nanotubes (NS-CNTs) were synthesized by a chemical reaction of ZnO nanoparticles with acid-treated SWCNTs and then dissolving ZnO through chemical etching. The unique structure of distorted hexagonal NS-CNTs encircled around ZnO nanoparticles was formed by the bending of SWCNTs caused by the agglomeration of chemically adsorbed Zn(OH)2, which is further crystallized as the polycrystalline ZnO inner core. The highly dispersible NS-CNTs could be incorporated in the poly[(vinylidenefluoride-co-trifluoroethylene] [P(VDF-TrFE)] copolymer, one of widely studied ferro- and piezo-electric polymer, up to the value of 15 wt% as nanofillers. The relative dielectric constant (K) of polymer nanocomposite, at 1 kHz, was greatly enhanced from 12.7 to the value of 62.5 at 11 wt% of NS-CNTs, corresponding to a 492% increase compared to that of pristine P(VDF-TrFE) with only a small dielectric loss tangent (D) of 0.1.

Trends in device utilization ratios in intensive care units over 10-year period in South Korea: device utilization ratio as a new aspect of surveillance.

BACKGROUND: Device-associated infection (DAI) is an important issue related to patient safety. It is important to reduce unnecessary device utilization in order to decrease DAI rates. AIM: To investigate the time trend of device utilization ratios (DURs) of voluntarily participating hospitals, collected over a 10-year period through the Korean National Healthcare-associated Infections Surveillance System (KONIS). METHODS: DURs from 2006 to 2015 in 190 intensive care units (ICUs) participating in KONIS were included in this study. DURs were calculated as the ratio of device-days to patient-days. The pooled incidences of DAIs and DURs were calculated for each year of participation, and the year-wise trends were analysed. FINDINGS: Year-wise ventilator utilization ratio (V-DUR) increased significantly from 0.40 to 0.41 (F = 6.27, P < 0.01), urinary catheter utilization ratio (U-DUR) increased non-significantly from 0.83 to 0.84 (F = 1.66, P = 0.10), and C-line utilization ratio (CL-DUR) decreased non-significantly from 0.55 to 0.51 (F = 1.62, P = 0.11). In the subgroup analysis, 'medical ICU' (F = 2.79, P < 0.01) and 'hospital with >900 beds' (F = 3.07, P < 0.01) were associated with the significant increase in V-DUR. CONCLUSION: In Korea, V-DUR showed a significant, year-wise increasing trend. The trends for U-DUR and CL-DUR showed no significant decrease. Efforts are required to ensure the reduction of DURs.

EMP2 is a novel therapeutic target for endometrial cancer stem cells.

Previous studies have suggested that overexpression of the oncogenic protein epithelial membrane protein-2 (EMP2) correlates with endometrial carcinoma progression and ultimately poor survival from disease. To understand the role of EMP2 in the etiology of disease, gene analysis was performed to show transcripts that are reciprocally regulated by EMP2 levels. In particular, EMP2 expression correlates with and helps regulate the expression of several cancer stem cell associated markers including aldehyde dehydrogenase 1 (ALDH1). ALDH expression significantly promotes tumor initiation and correlates with the levels of EMP2 expression in both patient samples and tumor cell lines. As therapy against cancer stem cells in endometrial cancer is lacking, the ability of anti-EMP2 IgG1 therapy to reduce primary and secondary tumor formation using xenograft HEC1A models was determined. Anti-EMP2 IgG1 reduced the expression and activity of ALDH and correspondingly reduced both primary and secondary tumor load. Our results collectively suggest that anti-EMP2 therapy may be a novel method of reducing endometrial cancer stem cells.

Validation of the Korean National Healthcare-associated Infections Surveillance System (KONIS): an intensive care unit module report.

BACKGROUND: National surveillance data should be validated to identify methodological problems within the surveillance programme and data quality issues. AIM: To test the validity of healthcare-associated infection (HAI) rate data from the Korean National Healthcare-associated Infections Surveillance System (KONIS). METHODS: Records from intensive care units of 12 (14.8%) of 81 participating hospitals for January-March 2014 were examined. The validation team reviewed 406 medical records of 110 patients with 114 reported HAIs - including 34 urinary tract infections (UTIs), 57 bloodstream infections (BSIs) and 23 cases of pneumonia (PNEU) - and 296 patients with no reported HAIs during one-day visits conducted in August and September 2014. The reviewers' diagnosis of HAI was regarded as the reference standard; in ambiguous cases, the KONIS Steering Committee confirmed the diagnosis of HAI. FINDINGS: Sensitivity values for UTIs, BSIs and PNEU were 85.3%, 74.0% and 66.7%, and specificity values were 98.7%, 99.1% and 98.7%, respectively. Positive predictive values were 85.3%, 94.7% and 78.3%, and negative predictive values were 98.7%, 94.6% and 97.7%, respectively. Sensitivity for PNEU was lower than that for UTIs and BSIs. The hospitals participating in KONIS infrequently reported conditions that were not HAIs. Sensitivity for BSIs was lower in this study than in KONIS validation studies conducted in 2008 and 2010. CONCLUSIONS: KONIS data are generally reliable; however, sensitivity for BSIs exhibited a decrease. This study shows the need for ongoing validation and continuous training of surveillance personnel to maintain the accuracy of surveillance data.

Population genetic characterization of the Japanese oak silkmoth, Antheraea yamamai (Lepidoptera: Saturniidae), using novel microsatellite markers and mitochondrial DNA gene sequences.

The Japanese oak silkmoth, Antheraea yamamai Guérin-Méneville, 1861 (Lepidoptera: Saturniidae), is an important natural resource of industrial value for silk fiber production. Owing to a lack of geographic and population genetic information, systematic domestication of An. yamamai has not been possible yet. In this study, 10 microsatellite markers developed using next-generation sequencing and two mitochondrial DNA (mtDNA) gene sequences (COI and ND4) were used to investigate the genetic variation and geographic structure of An. yamamai populations in South Korea. The two mtDNA gene sequences revealed very low total genetic variation and, consequently, low geographic variation, validating the use of more variable molecular markers. Genotyping of 76 An. yamamai individuals from nine localities in South Korea showed that the observed number of alleles at each locus ranged from 3 to 26, the polymorphism information content was 0.2990-0.9014, the observed and expected heterozygosities were 0.3252-0.9076 and 0.2500-0.9054, respectively, and FIS was -0.654-0.520. The population-based FIS, FST, RST, and global Mantel tests all suggested that the An. yamamai populations were overall well-interconnected, suggesting that any population can be used as a genetic source for domestication. Nevertheless, STRUCTURE analyses using microsatellite data and mtDNA sequences indicated the presence of two genetic pools in many populations, although a plausible explanation for this observation requires further studies.

Varied incidence of immediate adverse reactions to low-osmolar non-ionic iodide radiocontrast media used in computed tomography.

BACKGROUND: Low-osmolar non-ionic radiocontrast media (RCMs) are commonly used throughout hospitals. However, the incidence of immediate adverse drug reactions (ADRs) to various low-osmolar non-ionic RCMs is not well studied. We compared the incidence of immediate ADRs among different low-osmolar non-ionic RCMs used in computed tomography (CT). METHODS: Severance Hospital has collected data for adverse reactions occurring in-hospital using an internally developed system. Using this data, we reviewed 1969 immediate ADRs from 286 087 RCM-contrasted CT examinations of 142 099 patients and compared the immediate ADRs of iobitridol, iohexol, iopamidol, and iopromide. We analysed the incidence of immediate ADRs to different RCMs, as well as the effect of single or multiple CT examinations per day. RESULTS: Iopromide showed the highest incidence of immediate ADRs (1.03%) and was followed by iopamidol (0.67%), iohexol (0.64%), and iobitridol (0.34%). In cases of anaphylaxis, iopromide also showed the highest incidence (0.041%), followed by iopamidol (0.023%), iohexol (0.018%), and iobitridol (0.012%). Risk of immediate ADR due to multiple CT examinations (1.19%) was significantly higher than the risk due to a single CT examination (0.63%). Risk of anaphylaxis was also higher for multiple CT examinations (0.052%) than for a single CT examination (0.020%). CONCLUSIONS AND CLINICAL RELEVANCE: The incidence of immediate ADRs varied according to the low-osmolar non-ionic RCM used. Iopromide-induced immediate ADRs were more frequent, while iobitridol was associated with fewer immediate ADRs than other RCMs. Multiple CT examinations per day resulted in a higher incidence of immediate ADRs and anaphylaxis than a single CT examination. Clinicians should consider these risk differences of immediate ADRs when prescribing contrasted CT examinations.

A New Practical Desensitization Protocol for Oxaliplatin-Induced Immediate Hypersensitivity Reactions: A Necessary and Useful Approach.

BACKGROUND AND OBJECTIVE: Desensitization protocols for patients with immediate hypersensitivity reactions (IHSRs) have proven to be effective, but they are not widely used in clinical practice because of impracticalities such as high cost, long procedure duration, and a lack of trained personnel. We aimed to determine the clinical characteristics of oxaliplatin-induced IHSRs and assess measures to protect against these reactions and to validate a new practical desensitization protocol. METHODS: We retrospectively reviewed 2640 cases of oxaliplatin IHSRs in 271 oxaliplatin users and prospectively used a newly designed desensitization protocol 32 times in 12 patients with hypersensitivity to platinum-based chemotherapy. The protocol consisted of increases in infusion rate every 15 minutes, regardless of the concentration of the chemotherapy agent in the infusion bags. RESULTS: Of the 271 patients administered oxaliplatin, 45 (16.6%) experienced IHSRs. Of 39 patients who experienced an IHSR but needed to continue oxaliplatin, 6 (15.4%) stopped treatment due to the reaction, and 33 (84.6%) continued despite the risk of further reactions. The new desensitization protocol was successfully completed in 12 patients (100%), but it was ineffective in 3 patients (all with a negative skin prick test), who experienced fever without urticaria. CONCLUSIONS: Many patients who experience oxaliplatin-induced IHSRs are required to stop first-line oxaliplatin-based chemotherapy or to continue without desensitization, with the associated risks. Our new desensitization protocol is practical and easy to use in clinical practice.

The C/EBPδ protein is stabilized by estrogen receptor α activity, inhibits SNAI2 expression and associates with good prognosis in breast cancer.

Hypoxia and inflammatory cytokines like interleukin-6 (IL-6, IL6) are strongly linked to cancer progression, and signal in part through the transcription factor Ccaat/enhancer-binding protein δ (C/EBPδ, CEBPD), which has been shown to promote mesenchymal features and malignant progression of glioblastoma. Here we report a different role for C/EBPδ in breast cancer. We found that the C/EBPδ protein is expressed in normal breast epithelial cells and in low-grade cancers. C/EBPδ protein (but not mRNA) expression correlates with estrogen receptor (ER+) and progesterone receptor (PGR) expression and longer progression-free survival of breast cancer patients. Specifically in ER+ breast cancers, CEBPD-but not the related CEBPB-mRNA in combination with IL6 correlated with lower risk of progression. Functional studies in cell lines showed that ERα promotes C/EBPδ expression at the level of protein stability by inhibition of the FBXW7 pathway. Furthermore, we found that C/EBPδ attenuates cell growth, motility and invasiveness by inhibiting expression of the SNAI2 (Slug) transcriptional repressor, which leads to expression of the cyclin-dependent kinase inhibitor CDKN1A (p21CIP1/WAF1). These findings identify a molecular mechanism by which ERα signaling reduces the aggressiveness of cancer cells, and demonstrate that C/EBPδ can have different functions in different types of cancer. Furthermore, our results support a potentially beneficial role for the IL-6 pathway specifically in ER+ breast cancer and call for further evaluation of the role of intra-tumoral IL-6 expression and of which cancers might benefit from current attempts to target the IL-6 pathway as a therapeutic strategy.

Five-year decreased incidence of surgical site infections following gastrectomy and prosthetic joint replacement surgery through active surveillance by the Korean Nosocomial Infection Surveillance System.

BACKGROUND: Surveillance of healthcare-associated infection has been associated with a reduction in surgical site infection (SSI). AIM: To evaluate the Korean Nosocomial Infection Surveillance System (KONIS) in order to assess its effects on SSI since it was introduced. METHODS: SSI data after gastrectomy, total hip arthroplasty (THA), and total knee arthroplasty (TKA) between 2008 and 2012 were analysed. The pooled incidence of SSI was calculated for each year; the same analyses were also conducted from hospitals that had participated in KONIS for at least three consecutive years. Standardized SSI rates for each year were calculated by adjusting for SSI risk factors. SSI trends were analysed using the Cochran-Armitage test. FINDINGS: The SSI rate following gastrectomy was 3.12% (522/16,918). There was a significant trend of decreased crude SSI rates over five years. This trend was also evident in analysis of hospitals that had participated for more than three years. The SSI rate for THA was 2.05% (157/7656), which decreased significantly from 2008 to 2012. The risk factors for SSI after THA included the National Nosocomial Infections Surveillance risk index, trauma, reoperation, and age (60-69 years). The SSI rate for TKA was 1.90% (152/7648), which also decreased significantly during a period of five years. However, the risk-adjusted analysis of SSI did not show a significant decrease for all surgical procedures. CONCLUSION: The SSI incidence of gastrectomy and prosthetic joint replacement declined over five years as a result of active surveillance by KONIS.

Mesenteric vasculitis after G-CSF administration in a severe neutropenic patient with systemic lupus erythematosus.

Granulocyte colony-stimulating factor (G-CSF) is commonly used with neutropenic patients to accelerate recovery. G-CSF is a hematopoietic cytokine that regulates the proliferation and differentiation of neutrophil precursors, and is known as a safe and effective treatment for chemotherapy-induced neutropenia. However, we encountered a case in which a patient with systemic lupus erythematosus (SLE) developed mesenteric vasculitis after G-CSF administration. The patient was a 36-year-old female admitted with fever, arthralgia, and generalized erythematous rash. Despite symptomatic improvement with a high-dose steroid, severe neutropenia persisted for three weeks, precipitating a decision to use G-CSF to enhance recovery. Mesenteric vasculitis developed 15 hours after administration of G-CSF injection. Because the response of immune cells such as neutrophils and T cells is uncontrolled and dysfunctional in patients with lupus, G-CSF therapy should be used with caution.

Trends in the distribution and antimicrobial susceptibility of causative pathogens of device-associated infection in Korean intensive care units from 2006 to 2013: results from the Korean Nosocomial Infections Surveillance System (KONIS).

BACKGROUND: For all countries, information on pathogens causing healthcare-associated infections is important in order to develop proper strategies for preventing and treating nosocomial infections. AIM: To assess the change in frequencies and antimicrobial resistance of pathogens causing device-associated infections (DAIs) in intensive care units (ICUs) in South Korea between July 2006 and June 2014. METHODS: Data from the Korean Nosocomial Infections Surveillance System (KONIS) were analysed, including three major DAI types in ICUs. FINDINGS: The frequency of Gram-negative bacteria gradually increased for central line-associated bloodstream infection (CLABSI) and ventilator-associated pneumonia (VAP) (from 24.6% to 32.6% and from 52.8% to 73.5%, respectively). By contrast, the frequency of Gram-positive bacteria decreased from 58.6% to 49.2% for CLABSI, and from 44.3% to 23.8% for VAP (P < 0.001). Staphylococcus aureus was the most frequent causative pathogen in CLABSI throughout the surveillance period, but for VAP was replaced as the most frequent pathogen by Acinetobacter baumannii as of 2010. Candida albicans was the most frequent pathogen for catheter-associated urinary tract infection. The meticillin resistance rate in S. aureus decreased from 95% to 90.2% (P < 0.001); amikacin resistance in Klebsiella pneumoniae and Escherichia coli decreased from 43.8% to 14.7% and from 15.0% to 1.8%, respectively (P < 0.001); imipenem resistance in A. baumannii increased from 52.9% to 89.8% (P < 0.001). CONCLUSION: The proportion of Gram-negative bacteria as nosocomial pathogens for CLABSI and VAP has increased. The prevalence of A. baumannii causing DAIs in Korean ICUs has increased rapidly, as has the rate of carbapenem resistance in these bacteria.

Contrast-enhanced angiographic cone-beam computed tomography without pre-diluted contrast medium.

INTRODUCTION: Contrast-enhanced cone-beam computed tomography (CBCT) has been introduced and accepted as a useful technique to evaluate delicate vascular anatomy and neurovascular stents. Current protocol for CBCT requires quantitative dilution of contrast medium to obtain adequate quality images. Here, we introduce simple methods to obtain contrast-enhanced CBCT without quantitative contrast dilution. METHODS: A simple experiment was performed to estimate the change in flow rate in the internal carotid artery during the procedure. Transcranial doppler (TCD) was used to evaluate the velocity change before and after catheterization and fluid infusion. In addition, 0.3 cm(3)/s (n = 3) and 0.2 cm(3)/s (n = 7) contrast infusions were injected and followed by saline flushes using a 300 mmHg pressure bag to evaluate neurovascular stent and host arteries. RESULTS: Flow velocities changed -15 ± 6.8 % and +17 ± 5.5 % from baseline during catheterization and guiding catheter flushing with a 300 mmHg pressure bag, respectively. Evaluation of the stents and vascular structure was feasible using this technique in all patients. Quality assessment showed that the 0.2 cm(3)/s contrast infusion protocol was better for evaluating the stent and host artery. CONCLUSION: Contrast-enhanced CBCT can be performed without quantitative contrast dilution. Adequate contrast dilution can be achieved with a small saline flush and normal blood flow.

Trends in the incidence rate of device-associated infections in intensive care units after the establishment of the Korean Nosocomial Infections Surveillance System.

BACKGROUND: The effectiveness of continuous nationwide surveillance on healthcare-associated infections should be investigated in each country. AIM: To assess the rate of device-associated infections (DAIs) in intensive care units (ICUs) since the establishment of the Korean Nosocomial Infections Surveillance System (KONIS). METHODS: Nationwide data were obtained on the incidence rate of DAI in ICUs reported to KONIS by all participating hospitals. The three major DAIs were studied: ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CABSI), and catheter-associated urinary tract infection (CAUTI). The pooled and year-wise incidence rates (cases per 1000 device-days) of these DAIs were determined for the period 2006 and 2012. In addition, data from institutions that had participated in KONIS for at least three consecutive years were analysed separately. FINDINGS: The number of ICUs participating in KONIS gradually increased from 76 in 2006 to 162 in 2012. Between 2006 and 2012, the incidence rate per 1000 device-days for VAP decreased significantly from 3.48 to 1.64 (F = 11, P < 0.01), for CAUTI the rate decreased non-significantly from 1.85 to 1.26 (F = 2.02, P = 0.07), and for CABSI the rate also decreased non-significantly from 3.4 to 2.57 (F = 1.73, P = 0.12). In the 132 ICUs that had participated in KONIS for at least three consecutive years, the VAP rate significantly decreased from the first year to third year (F = 20.57, P < 0.01), but the rates of CAUTI (F = 1.06, P = 0.35) and CABSI (F = 1.39, P = 0.25) did not change significantly. CONCLUSION: The decreased incidence rate of VAP in ICUs in Korea might be associated with the continuous prospective surveillance provided by KONIS.

Generation of Charged Nanoparticles During Thermal Evaporation of Silver at Atmospheric Pressure.

The generation of charged silver nanoparticles in the gas phase during thermal evaporation of silver at atmospheric pressure was confirmed by the nano-differential mobility analyzer (DMA). Effects of the evaporation temperature, the nitrogen gas flow rate and the amount of silver to be evaporated on the size distribution of charged nanoparticles (CNPs) were examined. Both positively and negatively-charged nanoparticles were generated under all processing conditions adopted in this study. The deposition behavior of CNPs was affected by the gas flow, which is affected by the temperature gradient in the reactor and by the applied electric bias. The electric bias, which not only enhanced the film growth rate but also produced a much denser film surface, turned out to be an important process parameter under the condition where an appreciable amount of CNPs is generated.

NLRP3 inflammasome activation by mitochondrial ROS in bronchial epithelial cells is required for allergic inflammation.

Abnormality in mitochondria has been suggested to be associated with development of allergic airway disorders. In this study, to evaluate the relationship between mitochondrial reactive oxygen species (ROS) and NLRP3 inflammasome activation in allergic asthma, we used a newly developed mitochondrial ROS inhibitor, NecroX-5. NecroX-5 reduced the increase of mitochondrial ROS generation in airway inflammatory cells, as well as bronchial epithelial cells, NLRP3 inflammasome activation, the nuclear translocation of nuclear factor-κB, increased expression of various inflammatory mediators and pathophysiological features of allergic asthma in mice. Finally, blockade of IL-1ß substantially reduced airway inflammation and hyperresponsiveness in the asthmatic mice. These findings suggest that mitochondrial ROS have a critical role in the pathogenesis of allergic airway inflammation through the modulation of NLRP3 inflammasome activation, providing a novel role of airway epithelial cells expressing NLRP3 inflammasome as an immune responder.

A possible role of serum uric acid as a marker of metabolic syndrome.

BACKGROUND/AIMS: The association between serum uric acid (SUA) levels and metabolic syndrome (MetS) has recently been reported in several cross-sectional and longitudinal studies. We investigated SUA as a biomarker to predict future development of MetS in healthy Korean men without diabetes or hypertension and determined the optimal cut-off levels of SUA. METHODS: A retrospective cohort study was conducted using data from healthy men who received a general health check-up in 2003. A total of 1809 participants free of MetS, diabetes and hypertension was enrolled. Participants were classified into three groups based on SUA levels: group 1 (<5.5 mg/dL), group 2 (5.5-6.9 mg/dL) and group 3 (≥7.0 mg/dL). RESULTS: During 13,802 person-years of follow up, 127 participants developed MetS. After adjusting for multiple associated parameters, SUA was significantly associated with incident MetS (hazard ratios comparing groups 2 and 3 vs group 1, 2.45 and 3.47 respectively; P < 0.001). In receiver operating characteristic curve analysis, the optimal cut-off level for SUA to predict the development of MetS was 6.5 mg/dL. CONCLUSION: Our results indicate that an increased level of SUA, even within the normal range, is associated with future development of MetS in healthy middle-aged men.