Myelin toxicity of chlorhexidine in zebrafish larvae.

BACKGROUND: Chlorhexidine gluconate (CHG) is a topical antiseptic solution recommended for skin preparation before central venous catheter placement and maintenance in adults and children. Although CHG is not recommended for use in children aged <2 months owing to limited safety data, it is commonly used in neonatal intensive care units worldwide. We used zebrafish model to verify the effects of early-life exposure to CHG on the developing nervous system, highlighting its impact on oligodendrocyte development and myelination. METHODS: Zebrafish embryos were exposed to different concentrations of CHG from 4 h post fertilization to examine developmental toxicity. The hatching rate, mortality, and malformation of the embryos/larvae were monitored. Oligodendrocyte lineage in transgenic zebrafish embryos was used to investigate defects in oligodendrocytes and myelin. Myelin structure, locomotor behavior, and expression levels of genes involved in myelination were investigated. RESULTS: Exposure to CHG significantly induced oligodendrocyte defects in the central nervous system, delayed myelination, and locomotor alterations. Ultra-microstructural changes with splitting and fluid-accumulated vacuoles between the myelin sheaths were found. Embryonic exposure to CHG decreased myelination, in association with downregulated mbpa, plp1b, and scrt2 gene expression. CONCLUSION: Our results suggest that CHG has a potential for myelin toxicity in the developing brain. IMPACT: To date, the neurodevelopmental toxicity of chlorhexidine gluconate (CHG) exposure on the developing brains of infants remains unknown. We demonstrated that CHG exposure to zebrafish larvae resulted in significant defects in oligodendrocytes and myelin sheaths. These CHG-exposed zebrafish larvae exhibited structural changes and locomotor alterations. Given the increased CHG use in neonates, this study is the first to identify the risk of early-life CHG exposure on the developing nervous system.

Particulate matter induces arrhythmia-like cardiotoxicity in zebrafish embryos by altering the expression levels of cardiac development- and ion channel-related genes.

Air pollution is a risk factor that increases cardiovascular morbidity and mortality. In this study, we investigated the cardiotoxicity of particulate matter (PM) exposure using a zebrafish embryo model. We found that PM exposure induced cardiotoxicity, such as arrhythmia, during cardiac development. PM exposure caused cardiotoxicity by altering the expression levels of cardiac development (T-box transcription factor 20, natriuretic peptide A, and GATA-binding protein 4)- and ion-channel (scn5lab, kcnq1, kcnh2a/b, and kcnh6a/b)-related genes. In conclusion, this study showed that PM induces the aberrant expression of cardiac development- and ion channel-related genes, leading to arrhythmia-like cardiotoxicity in zebrafish embryos. Our study provides a foundation for further research on the molecular and genetic mechanisms of cardiotoxicity induced by PM exposure.

Association of delayed initiation of non-invasive respiratory support with pulmonary air leakage in outborn late-preterm and term neonates.

The frequency of non-invasive respiratory support use has increased in neonates of all gestational ages with respiratory distress (RD). However, the impact of delayed initiation of non-invasive respiratory support in outborn neonates remains poorly understood. This study aimed to identify the impact of the delayed initiation of non-invasive respiratory support in outborn, late-preterm, and term neonates. Medical records of 277 infants (gestational age of ≥ 35 weeks) who received non-invasive respiratory support as primary respiratory therapy < 24 h of age between 2016 and 2020 were retrospectively reviewed. Factors associated with respiratory adverse outcomes were investigated in 190 outborn neonates. Infants with RD were divided into two groups: mild (fraction of inspired oxygen [FiO2] ≤ 0.3) and moderate-to-severe RD (FiO2 > 0.3), depending on their initial oxygen requirements from non-invasive respiratory support. The median time for the initiation of non-invasive respiratory support at a tertiary center was 3.5 (2.2-5.0) h. Male sex, a high oxygen requirement (FiO2 > 0.3), high CO2 level, and respiratory distress syndrome were significant factors associated with adverse outcomes. Subgroup analysis revealed that in the moderate-to-severe RD group, delayed commencement of non-invasive respiratory support (≥ 3 h) was significantly associated with pulmonary air leakage (p = 0.033). CONCLUSION: Our study shows that outborn neonates with moderate-to-severe RD, who were treated with delayed non-invasive respiratory support, were associated with an increased likelihood of pulmonary air leakage. Additional prospective studies are required to establish the optimal timing and methods of non-invasive respiratory support for outborn, late-preterm, and term infants. WHAT IS KNOWN: • Non-invasive respiratory support is widely used in neonates of all gestational ages. • Little is known on the impact of delayed initiation of non-invasive respiratory support in outborn, late preterm, and term neonates. WHAT IS NEW: • Male sex, high oxygen requirement (FiO2 >0.3), high initial CO2 level, and respiratory distress syndrome significantly correlated with adverse outcomes. • Outborn late-preterm and term neonates with high oxygen requirement who were treated with delayed non-invasive respiratory support indicated an increased likelihood of pulmonary air leakage.

6,4'-dihydroxy-7-methoxyflavanone protects against H2O2-induced cellular senescence by inducing SIRT1 and inhibiting phosphatidylinositol 3-kinase/Akt pathway activation.

6, 4'-Dihydroxy-7-methoxyflavanone (DMF) has been shown to possess anti-inflammatory, anti-oxidative, and neuroprotective activities. However, its effect on oxidative stress-induced aging remains undemonstrated. This study aimed at investigating the anti-senescence effect of DMF on hydrogen peroxide (H2O2)-induced premature senescence, and associated molecular mechanisms in human dermal fibroblasts (HDFs). The cells were DMF pretreated with small interfering RNA (siRNAs) of control or sirtuin 1 (SIRT1) before H2O2 exposure, and western blot analysis, senescence-associated ß-galactosidase (SA-ß-gal) activity, cell counting, gene silencing, and SIRT1 activity assay were performed. Pretreatment with DMF inhibited H2O2-induced senescence phenotypes, which showed decreased SA-ß-gal activity and increased cell growth in comparison with H2O2-treated HDFs. Meanwhile, the decreases in ac-p53, p21Cip1/WAF1, and p16Ink4a and the increases in pRb and cyclin D1 were observed. DMF was also found to induce SIRT1 expression and activity level concentration- and time-dependently. Moreover, SIRT1 inhibition abrogated DMF senescence prevention. Additionally, Akt and ERK were activated with different kinetics after H2O2 exposure, and Akt activity inhibition attenuated SA-ß-gal activity augmentation. We also found that DMF inhibited H2O2-induced Akt phosphorylation. This study indicates that DMF effectively protects against oxidative stress-induced premature senescence through SIRT1 expression up-regulation and Akt pathway inhibition in HDFs. These results suggest that DMF can be a potential therapeutic molecule for age-related diseases, or a protective agent against the aging process.

Hemodynamics of different volumes of red blood cell transfusion in preterm infants.

BACKGROUND: Although many controversies exist regarding the risk of red blood cell (RBC) transfusions, half of preterm infants born at <32 weeks of gestational age receive such transfusions because of anemia of prematurity. Because of the costs and risks associated with multiple transfusions, it has been suggested that a large transfusion volume reduces the number of transfusions. However, there have been persistent concerns that RBC transfusion might lead to volume overload. METHODS: We examined the impacts of large (20 mL/kg) compared to standard volume (15 mL/kg) transfusions on the hemodynamic variables of stable, electively transfused, preterm infants, by serially measuring echocardiographic parameters and plasma B-type natriuretic peptide levels. RESULTS: A total of 39 infants born at <34 weeks of gestation and aged >2 weeks at the time of enrollment were randomly allocated to either a standard volume (15 mL/kg) or a large volume (20 mL/kg) group. Significant reductions in cardiac output and transient increases in plasma B-type natriuretic peptide levels were found after RBC transfusion in both the standard and large volume (20 mL/kg) groups. However, these changes were not significantly different between the two groups. CONCLUSIONS: Large-volume transfusions could be tolerable in stable preterm infants with anemia.

Luteolin inhibits H2O2-induced cellular senescence via modulation of SIRT1 and p53.

Luteolin, a sort of flavonoid, has been reported to be involved in neuroprotective function via suppression of neuroinflammation. In this study, we investigated the protective effect of luteolin against oxidative stress-induced cellular senescence and its molecular mechanism using hydrogen peroxide (H2O2)-induced cellular senescence model in House Ear Institute-Organ of Corti 1 cells (HEI-OC1). Our results showed that luteolin attenuated senescent phenotypes including alterations of morphology, cell proliferation, senescence-associated ß-galactosidase expression, DNA damage, as well as related molecules expression such as p53 and p21 in the oxidant challenged model. Interestingly, we found that luteolin induces expression of sirtuin 1 in dose- and time-dependent manners and it has protective role against H2O2-induced cellular senescence by upregulation of sirtuin 1 (SIRT1). In contrast, the inhibitory effect of luteolin on cellular senescence under oxidative stress was abolished by silencing of SIRT1. This study indicates that luteolin effectively protects against oxidative stress-induced cellular senescence through p53 and SIRT1. These results suggest that luteolin possesses therapeutic potentials against age-related hearing loss that are induced by oxidative stress.

Isoparvifuran isolated from Dalbergia odorifera attenuates H2O2-induced senescence of BJ cells through SIRT1 activation and AKT/mTOR pathway inhibition.

Isoparvifuran is a benzofuran compound isolated from the heartwood of Dalbergia odorifera. Related research reported that isoparvifuran has antioxidant property. However, it is unclear whether isoparvifuran has anti-aging effects. In this research, we established an aging model, hydrogen peroxide (H2O2)-induced BJ cell senescence, to explore the protective effect of isoparvifuran on cell senescence and its related mechanisms. Our results revealed that isoparvifuran obviously attenuated H2O2-induced cell senescence, increased the cell proliferation rate,and reversed senescence-associated molecular markers expression such as cyclin D1, pRb, caveolin-1, ace-p53, p21 and p16. Moreover, isoparvifuran dose and time dependently increased the expression level of Sirtuin 1 (SIRT1) in BJ cells. The inhibition of SIRT1 obviously reversed the reduction of SA-ß-gal activity and the alteration of senescence-associated molecular markers induced by isoparvifuran. Additionally, isoparvifuran also inhibited H2O2-induced AKT and S6 phosphorylation and increase of SA-ß-gal activity. In summary, isoparvifuran protects BJ cells from H2O2-induced premature senescence, the anti-senescence effect of isoparvifuran is associated with the activation of SIRT1 and the suppression of AKT/mTOR signaling pathway.

Latifolin Inhibits Oxidative Stress-Induced Senescence via Upregulation of SIRT1 in Human Dermal Fibroblasts.

Latifolin, a natural flavonoid found in Dalbergia odorifera T. Chen, has been reported to exhibit anti-inflammatory and anticarcinogenic activities in vitro. However, the anti-aging effects of latifolin are unknown. In this study, we selected a model in vitro system, hydrogen peroxide (H2O2)-induced senescence in human dermal fibroblasts (HDFs), to examine the protective effects of latifolin against senescence and the detailed molecular mechanisms involved. Latifolin reversed the senescence-like phenotypes of the oxidant-challenged model, including senescence-associated ß-galactosidase (SA-ß-gal) staining, cell proliferation, and the expression of senescence-related proteins, such as caveolin-1, ac-p53, p21Cip1/WAF1, p16Ink4α, pRb, and cyclinD1. We also found that latifolin induced the expression of silent information regulator 1 (SIRT1) in a concentration- and time-dependent manner, and the anti-senescence effect of latifolin was abrogated by SIRT1 inhibition. Latifolin also suppressed the activation of Akt and S6K1 and attenuated the increase in SA-ß-gal activity after H2O2 exposure. Our results indicate that latifolin exerts protective effects against senescence in HDFs and that induction of SIRT1 and inhibition of the mammalian target of rapamycin (mTOR) pathway are key mediators of its anti-aging effects.

Effectiveness of nCPAP for moderate preterm infants compared to BiPAP: A Randomized, Controlled Non-Inferiority Trial.

BACKGROUND: Bilevel positive airway pressure (BiPAP) has recently been used in preterm infants with respiratory distress as an alternative to nasal continuous positive airway pressure (nCPAP) because, theoretically, BiPAP is thought to be more effective than nCPAP. However, the results of some studies comparing nCPAP with BiPAP as the initial respiratory support were controversial. The aim of this study is to compare the clinical effectiveness and safety of nCPAP with BiPAP at gestational ages of 30+0 to 34+6  weeks. METHODS: A total of 93 infants with gestational ages of 30+0 to 34+6  weeks, who presented with respiratory distress within 24 h after birth, were randomized to the nCPAP group or the BiPAP group. The primary outcome was the incidence of treatment failure with these two non-invasive respiratory support devices. Criteria for treatment failure included any of the following: respiratory acidosis (PaCO2 >65 mmHg with pH <7.2), hypoxia (FiO2 >0.4), or apnea (>2-3 episodes of apnea/h). RESULTS: There was no statistically significant difference in treatment failure between the two groups (P = 0.576). The risk difference comparing treatment failure rate between nCPAP and BiPAP groups was -4.7% (95% CI: -21.5-11.9). CONCLUSIONS: Nasal continuous positive airway pressure is not inferior to BiPAP as an initial management of respiratory distress in these premature infants. We therefore conclude that nCPAP can be used as an initial management for preterm infants at gestational age of between 30 and 35 weeks as a substitute for BiPAP.

Effect of Angelica gigas Nakai Ethanol Extract and Decursin on Human Pancreatic Cancer Cells.

Pancreatic cancer (PC) is one of the most severe cancers, and its incidence and mortality rates have steadily increased in the past decade. In this study, we demonstrate the effect of Angelica gigas Nakai extract on pancreatic ductal adenocarcinoma cells. We prepared A. gigas Nakai ethanol extract (AGE) using roots of A. gigas Nakai and detected its active compound decursin from AGE by ultra-performance liquid chromatography analysis. AGE and decursin significantly decreased viability and colony formation of PANC-1 and MIA PaCa-2 cells. AGE and decursin induced G0/G1 phase arrest through downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). Caspase-3-dependent apoptosis of PANC-1 cells was promoted by AGE and decursin. Additionally, nontoxic concentrations of AGE and decursin treatment could suppress matrix metalloproteinase (MMP)-2 and MMP-9 expression and activity by inhibiting p38 phosphorylation. Taken together, this study demonstrates that AGE and decursin have potential properties to be considered in PC treatment.

The first case of congenital blood chimerism in two of the triplets in Korea.

BACKGROUND: Chimeras are composed of two or more different populations that originated from different zygotes. Blood chimerism arising from twins have been reported in the literature. Herein, we report the first blood group chimerism in triplets. METHODS: ABO blood grouping was carried out by manual tile methods (Merck Millipore, UK) and micro-column agglutination method (Bio-Rad, Cressier sur Morat, Switzerland). Flow cytometric analysis was performed with Anti-A-PE conjugated monoclonal antibodies (BD Biosciences, San Jose, CA, USA) and FACS Canto II (BD Biosciences). Molecular analysis was performed with allele-specific polymerase chain reaction (AS-PCR) and direct sequencing of the exons 6 and 7. RESULTS: Mixed-field agglutination and weak agglutination against anti-A were revealed by ABO blood grouping. Flow cytometric analysis revealed the presence of both A cells and O cells. AS-PCR and sequencing showed two neonates with chimerism, with each neonate`s genotype being A102/O01/O02. CONCLUSION: This is the first recorded case of blood chimera from a triplet in Korea. We recommend full investigation of blood group chimerism in neonates with ABO discrepancy, as blood chimerism is subject to certain caution in the clinical environment.

Hemodynamic Effects on Systemic Blood Flow and Ductal Shunting Flow after Loading Dose of Intravenous Caffeine in Preterm Infants according to the Patency of Ductus Arteriosus.

BACKGROUND: In preterm infants, caffeine citrate is used to stimulate breathing before they are weaned from mechanical ventilation and to reduce the frequency of apnea. In recent studies, effects of caffeine on the cardiovascular system have been emphasized in preterm infants with patent ductus arteriosus (PDA). METHODS: This study aimed to assess the short-term hemodynamic effects on systemic blood flow and ductal shunting flow after loading standard doses of intravenous caffeine in preterm infants. Echocardiographic studies were performed by a single investigator, before and at 1 hour and 4 hours after an intravenous infusion of a loading dose as 20 mg/kg caffeine citrate for 30 minutes. RESULTS: In 25 preterm infants with PDA, left ventricular output decreased progressively during 4 hours after caffeine loading. Superior vena cava (SVC) flow decreased and ductal shunting flow increased at 1 hour and then recovered at 4-hour to baseline values. A diameter of PDA significantly decreased only at 4-hour after caffeine loading. There were no significant changes of these hemodynamic parameters in 29 preterm infants without PDA. CONCLUSION: In preterm infants with PDA, a standard intravenous loading dose of 20 mg/kg caffeine citrate was associated with increasing ductal shunting flow and decreasing SVC flow (as a surrogate for systemic blood flow) 1 hour after caffeine loading, however, these hemodynamic parameters recovered at 4 hours according to partial constriction of the ductus arteriosus. Close monitoring of hemodynamic changes would be needed to observe the risk for pulmonary over-circulation or systemic hypo-perfusion due to transient increasing ductal shunting flow during caffeine loading in preterm infants with PDA.

Chronological Echocardiographic Changes in Healthy Term Neonates within Postnatal 72 Hours Using Doppler Studies.

BACKGROUND: This study evaluated echocardiographic changes in full-term healthy neonates during early transitional period from postnatal 0-72 hours at 12-hour intervals by echocardiography. METHODS: This was a prospective, observational, and longitudinal single-center cohort study. Morphometric, functional, systolic, diastolic, and tissue Doppler imaging (TDI) parameters (patent ductus arteriosus [PDA], aorta, superior vena cava [SVC], stroke volume [SV], cardiac output [CO], cardiac index [CI], early diastolic flow velocity [E], late diastolic flow velocity [A], early filling in TDI [E'], peak systolic annular velocity in TDI [S'], late velocity peak in TDI [A'], and myocardial performance index [MPI]) were evaluated in left ventricle (LV) and right ventricle (RV) with 56 newborns. RESULTS: Sizes and peak velocities of PDA before postnatal 24 hours were significantly changed than those after postnatal 24 hours. Aortic velocity time integral (VTI), systolic blood pressure (BP), LV SV/kg, LV CO/kg, LV CI, and SVC flow/LV CO before 24 hours showed significantly changes than those after 24 hours. Also, LV and RV MPI before 24 hours were significantly higher than those after 24 hours. LV E/E' was significantly higher than RV E/E'. CONCLUSION: Postnatal 24 hours is critical time for hemodynamic closure of PDA because aortic VTI, systolic BP, LV SV, LV CO, LV CI, and SVC flow/LV CO showed simultaneously significant changes after 24 hours at the same time as 24 hours of physiological closure of PDA. Chronological and dramatic changes of systolic, diastolic, and TDI parameters during early postnatal period can be used to compile normal baseline data of healthy full-term neonates.

Effect of socio-economic status on sleep.

AIM: Sufficient sleep is an important factor in physical and mental health. Sleep duration can be affected by socio-economic status (SES). This study aimed to examine the association between sleep duration and SES in Korean adolescents. METHODS: This study was conducted with 1608 adolescents aged 12-18 years, based on data from the 2010 to 2012 Korean National Health and Nutrition Examination Survey (KNHANES). Sleep duration was self-reported in hours and three SES indicators were used: household income, basic livelihood security programmes and type of health insurance. Confounding factors in this study were age, mental health and physical activity. RESULTS: Participants' average age was 15.6 ± 0.05 years and average sleep duration was 7.04 ± 0.05 h. There was a strong association between sleep duration and household income (P < 0.05) rather than other socio-economic indicators. In addition, it showed that sleep duration was significantly associated with age, body mass index (P < 0.05) and low mood is associated with short sleep and long sleep (>9 h/night). We found similar results in both genders, that is, that the highest income group had shorter sleep duration than the lowest income group. CONCLUSIONS: This study shows that the SES, particularly household income, is an important factor in short sleep duration in Korean adolescents. Our findings suggest that, in future investigations of the adolescent's sleep problem, attention should be paid to household income.

Humidified High Flow Nasal Cannula versus Nasal Continuous Positive Airway Pressure as an Initial Respiratory Support in Preterm Infants with Respiratory Distress: a Randomized, Controlled Non-Inferiority Trial.

Heated, humidified, high-flow nasal cannula (HHFNC) is frequently used as a noninvasive respiratory support for preterm infants with respiratory distress. But there are limited studies that compares HHFNC with nasal continuous positive airway pressure (nCPAP) only as the initial treatment of respiratory distress in preterm infants immediately after birth. The aim of this study is to assess the effectiveness and safety of HHFNC compared to nCPAP for the initial treatment of preterm infants with respiratory distress. Preterm infants at between 30 and 35 weeks of gestational age were randomized to HHFNC or nCPAP when they showed respiratory distress in less than 24 hours of age postnatally. Preterm infants who needed invasive respiratory supports were excluded. Primary outcome was the incidence of treatment failure (defined as need for the intubation or mechanical ventilation). Eighty-five infants were analyzed. Sixteen of 42 infants randomized to HHFNC showed treatment failure compared to 9 of 43 infants using nCPAP (Risk difference 17.17 [-1.90-36.23]; P = 0.099). In terms of the reason for treatment failure, the frequency of hypoxia was significantly higher in the HHFNC group than in the nCPAP group (P = 0.020). There was no difference between the 2 groups in terms of respiratory and clinical outcomes and complications. Although HHFNC is safe compared to nCPAP, it is not certain that HHFNC is effective compared to nCPAP non-inferiorly as an initial respiratory support in preterm infants with respiratory distress.

Effect of the prenatal maternal environments and diets on cord blood interleukin-4 and interferon -gamma: A pilot study.

BACKGROUND AND OBJECTIVE: TThe environment of a pregnant woman can affect not only fetal growth and development, but also diseases in childhood. Neonatal cord blood cytokines are commonly used to evaluate the immune development of neonates. The purpose of this study was to evaluate the effects of the environment and diet during pregnancy on IL-4 and IFN-γ in neonatal cord blood. METHOD: A total of 111 pregnant women participated in this study from April to November 2010. Allergy history, sensitization assessed by the skin prick test, dietary intake and indoor environment were evaluated. IL-4 and IFN-γ levels were measured in the complete cord blood of neonates using real-time PCR. RESULTS: There were 54 pregnant women with allergic disease. Both IL-4 and IFN-γ levels in neonatal cord blood were higher in samples from allergic mothers than in non-allergic mothers (p<0.05). The indoor environment and nutrient intake were not different between allergic and non-allergic mothers, except regarding carpet use. When the cytokine levels were divided into quartiles, lower folate and vitamin B6 intake was associated with the highest levels of IL-4 in neonatal cord blood (p<0.05), and higher folate and vitamin B6 intake was associated with highest levels of IFN-γ in neonatal cord blood. CONCLUSIONS: In this study, a strong association between IL-4 and IFN-γ levels in cord blood and the intake of folate and vitamin B6 was found, which indicates that food intake during pregnancy might have a strong influence on IL-4 and IFN-γ levels in cord blood, to a greater extent than environmental factors.

Arctigenin Inhibits Lung Metastasis of Colorectal Cancer by Regulating Cell Viability and Metastatic Phenotypes.

Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, ß-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.

Plasma neutrophil gelatinase-associated lipocalin predicts acute pyelonephritis in children with urinary tract infections.

BACKGROUND: The identification of acute pyelonephritis (APN) is still a challenge. METHODS: Patients admitted for their first urinary tract infection (UTI) were enrolled. Plasma neutrophil gelatinase-associated lipocalin (NGAL) levels were measured at admittance and after treatment. Laboratory, clinical, and imaging results were compared between children with and without APN. RESULTS: A total of 123 patients were enrolled (53 APN and 70 lower UTI). After adjusting for age and gender, plasma NGAL levels were higher in the APN group than in the lower UTI group (233 (129-496) ng/ml vs. 71 (50.8-110) ng/ml, P < 0.001). NGAL levels were correlated with the serum levels of leukocytes, C-reactive protein, and creatinine, as well as fever duration (P < 0.05). Multivariable analysis revealed that log-transformed plasma NGAL was an independent predictor of APN (P < 0.05). Receiver operating curve analysis showed a good diagnostic profile of NGAL for identifying APN (area under the curve 0.864) with a best cut-off value of 102.5 ng/ml. The NGAL levels in both two groups decreased after treatment compared to levels before treatment (P < 0.001). CONCLUSION: Plasma NGAL can be a sensitive predictor for identifying APN and monitoring the treatment response of pediatric UTI.

Clinical significance of platelet-associated hematological parameters as an early supplementary diagnostic tool for sepsis in thrombocytopenic very-low-birth-weight infants.

Sepsis is an important cause of death in very-low-birth-weight (VLBW) neonates. Although conventional diagnostic indicator of sepsis has been done by blood cultures, this took much longer time. The measurement of platelet-associated parameters such as mean platelet volume (MPV) and platelet distribution width (PDW) become more reliable and accurate parameters as a non-specific marker for sepsis. Our objective is to examine the usefulness of those platelet hematological parameters as a supplementary diagnostic tool for sepsis in VLBW infants. This study is a retrospective cohort study of neonates subject to the diagnosis of sepsis from October 2006 to July 2010. This study was conducted at Korea University medical center. We studied total 2,336 infants for 32 days from birth (Day 0) to Day 31. We compared three groups of infants to examine differences of platelet parameters according to their age from birth to Day 31: (i) full-terms versus VLBW without sepsis, (ii) VLBW without sepsis versus VLBW with sepsis and (iii) thrombocytopenic VLBW without sepsis versus those with sepsis. The platelet-associated parameters were significantly distinguishable between septic and non-septic groups at their early age (∼ 1 week), especially platelet counts (PLT) (p = 0.0091), MPV (p = 0.007) and PDW (p = 0.0372) in thrombocytopenic VLBW infants. The decreased PLT, elevated MPV and PDW were major characteristics of septic group. We suggested maximum cutoff values of the platelet factors by performing receiver operating characteristic curve analysis between septic and non-septic thrombocytopenic VLBW infants, among which MPV was the most promising index (AUCMPV = 0.7044 > AUCPLT = 0.6921 > AUCPDW = 0.6593). Platelet-associated hematological parameters are useful for the early diagnosis of sepsis as a more efficient and supplementary diagnostic method in thrombocytopenic VLBW infants.

Current Status of Therapeutic Strategies for Patent Ductus Arteriosus in Very-Low-Birth-Weight Infants in Korea.

This study aimed to investigate current therapeutic strategies for patent ductus arteriosus (PDA) in very-low-birth-weight (VLBW) infants in Korea. A total of 2,254 VLBW infants among 2,386 from Korean Neonatal Network cohort born from January 2013 to June 2014 were included. No PDA was seen for 1,206 infants (53.5%) and the infants diagnosed or treated for PDA were 1,048 infants (46.5%). The proportion of infants with PDA was decreased according to the increase in gestational age (GA) and birthweight. Infants with PDA were divided into groups according to the therapeutic strategies of PDA: prophylactic treatment (PT, n = 69, 3.1%), pre-symptomatic treatment (PST, n = 212, 9.4%), symptomatic treatment (ST, n = 596, 26.4%), and conservative treatment (CT, n = 171, 7.6%). ST was the most preferred treatment modality for preterm PDA and the proportion of the patients was decreased in the order of PST, CT, and PT. Although ST was still the most favored treatment in GA < 24 weeks group, CT was more preferred than PST or ST when compared with GA ≥ 32 weeks group [CT vs. PST, OR 5.3, 95% CI 1.56-18.18; CT vs. ST, OR 2.9, 95% CI 1.03-8.13]. A total of 877 infants (38.9%) received pharmacological or surgical treatment about PDA, and 35.5% (801 infants) received pharmacological treatment, mostly with ibuprofen. Seventy-six infants (3.4%) received primary ligation and 8.9% (201 infants) received secondary ligation. Diverse treatment strategies are currently used for preterm PDA in Korea. Further analyses of neonatal outcomes according to the treatment strategies are necessary to obtain a standardized treatment guideline for preterm PDA.