The Impact of an Antimicrobial Stewardship Program on Days of Therapy in the Pediatric Center: An Interrupted Time-Series Analysis of a 19-Year Study.

BACKGROUND: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. METHODS: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001-2008) and the post-intervention (2009-2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patient-days, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ². RESULTS: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = -16.5; 95% confidence interval [CI], -30.6 to -2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). CONCLUSION: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Antidiabetic Effect of Fermented Mesembryanthemum crystallinum L. in db/db Mice Involves Regulation of PI3K-Akt Pathway.

Type 2 diabetes (T2D) is a serious health issue with increasing incidences worldwide. However, current medications have limitations due to side effects such as decreased appetite, stomach pain, diarrhea, and extreme tiredness. Here, we report the effect of fermented ice plant (FMC) in the T2M mouse model of db/db mice. FMC showed a greater inhibition of lipid accumulation compared to unfermented ice plant extract. Two-week oral administration with FMC inhibited body weight gain, lowered fasting blood glucose, and improved glucose tolerance. Serum parameters related to T2D including insulin, glycosylated hemoglobin, adiponectin, and cholesterols were improved as well. Histological analysis confirmed the protective effect of FMC on pancreas and liver destruction. FMC treatment significantly increased the expression and phosphorylation of IRS-1, PI3K, and AKT. Additionally, AMP-activated protein kinase phosphorylation and nuclear factor erythroid 2-related factor 2 were also increased in the liver tissues of db/db mice treated with FMC. Overall, our results indicate the anti-diabetic effect of FMC; therefore, we suggest that FMC may be useful as a therapeutic agent for T2D.

Neuroprotective Effects of Water Extract from Brown Algae Petalonia binghamiae in an Experimental Model of Focal Cerebral Ischemia In Vitro and In Vivo.

Focal cerebral ischemia (fCI) can result in brain injury and sensorimotor deficits. Brown algae are currently garnering scientific attention as potential therapeutic candidates for fCI. This study investigated the therapeutic effects of the hot water extract of Petalonia binghamiae (wPB), a brown alga, in in vitro and in vivo models of fCI. The neuroprotective efficacy of wPB was evaluated in an in vitro excitotoxicity model established using HT-22 cells challenged with glutamate. Afterward, C57/BL6 mice were administered wPB for 7 days (10 or 100 mg/kg, intragastric) and subjected to middle cerebral artery occlusion and reperfusion (MCAO/R) operation, which was used as an in vivo fCI model. wPB co-incubation significantly inhibited cell death, oxidative stress, and apoptosis, as well as stimulated the expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, and the nuclear translocation of its upstream regulator, nuclear factor erythroid 2-related factor 2 (Nrf2) in HT-22 cells challenged with glutamate-induced excitotoxicity. Pretreatment with either dose of wPB significantly attenuated infarction volume, neuronal death, and sensorimotor deficits in an in vivo fCI model. Furthermore, the attenuation of oxidative stress and apoptosis in the ischemic lesion accompanied the wPB-associated protection. This study suggests that wPB can counteract fCI via an antioxidative effect, upregulating the Nrf2/HO-1 pathway.

Double-barreled IMA-M2 and STA-MCA bypass in severe stenosis of terminal internal carotid artery: three case reports.

EC-IC bypasses have been performed to treat complex aneurysms or moyamoya disease or atherosclerotic steno-occlusive disease. We report the three cases that underwent EC-IC revascularization of the IMA-M2 bypass using the radial artery graft concurrently after the STA-MCA anastomosis to prevent potential ischemic damage during the operation and augment more flow in terminal internal carotid artery stenosis. All patients experienced neither perioperative complications nor further events for a 3-month follow-up. The double-barreled IMA-M2 and STA-MCA bypass is a good option for substantial amount of EC-IC revascularization with minimizing ischemic injury and maximizing flow amount in patients with severe hemodynamic compromise.

Feasibility and safety values of activated clotting time-guided systemic heparinization in coil embolization for unruptured intracranial aneurysms.

OBJECTIVE: This study aimed to evaluate the feasibility and safety values of activated clotting time (ACT)-guided systemic heparinization in reducing periprocedural thrombosis and bleeding complications during coil embolization of unruptured intracranial aneurysms. METHODS: A total of 228 procedures performed on 213 patients between 2016 and 2021 were included in the retrospective analysis. The target ACT was set at 250 s. Logistic regression was performed to assess predictors for the occurrence of thrombosis and bleeding. Receiver operating characteristic (ROC) analyses were employed to determine the optimal cut-off values for ACT, heparinization, and procedure time. RESULTS: Most (85.1%) of procedures were stent-assisted embolization. The mean baseline ACT was 128.8 ± 45.7 s. The mean ACT at 20 min after the initial intravenous heparin loading of 78.2 ± 18.8 IU/kg was 185 ± 46.4 s. The mean peak ACT was 255.6 ± 63.8 s with 51.3% (117 cases) achieving the target ACT level. Peak ACT was associated with symptomatic thrombosis (OR per second, 1.008; 95% CI, 1.000-1.016; P = 0.035) (cut-off value, 275 s; area under ROC (AUROC), 0.7624). Total administered heparin dose per body weight was negatively associated with symptomatic thrombosis (OR per IU/kg, 0.972; 95% CI, 0.949-0995; P = 0.018) (cut-off value, 294 IU/kg; AUROC, 0.7426) but positively associated with significant bleeding (OR, 1.008 per IU/kg; 95% CI, 1.005-1.012; P <0 .001) (cut-off value, 242 IU/kg; AUROC, 0.7391). Procedure time was significantly associated with symptomatic thrombosis (OR per minute, 1.05; 95% CI, 1.017-1.084; P value = 0.002) (cut-off value, 158 min; area under ROC, 0.8338). CONCLUSION: This study demonstrated that ACT-guided systemic heparinization was feasible to achieve the target ACT value and proposes probable safety thresholds to prevent periprocedural complications through reducing procedure time during coil embolization of unruptured intracranial aneurysms in the stent era.

The Multifaceted Clinical Characteristics of Congenital Cytomegalovirus Infection: From Pregnancy to Long-Term Outcomes.

BACKGROUND: The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery. METHODS: This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated. RESULTS: The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6-40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir. CONCLUSION: Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.

Perilla frutescens Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation.

Vascular dementia (VaD) is characterized by a time-dependent memory deficit and essentially combined with evidence of neuroinflammation. Thus, polyphenol-rich natural plants, which possess anti-inflammatory properties, have received much scientific attention. This study investigated whether Perilla frutescens leaf extract (PFL) exerts therapeutic efficacy against VaD. Sprague Dawley rats were divided into five groups: SO, sham-operated and vehicle treatment; OP, operated and vehicle treatment; PFL-L, operated and low-dose (30 mg/kg) PFL treatment; PFL-M, operated and medium-dose (60 mg/kg) PFL treatment; and PFL-H, operated and high-dose (90 mg/kg) PFL treatment. Two-vessel occlusion and hypovolemia (2VO/H) were employed as a surgical model of VaD, and PFL was given orally perioperatively for 23 days. The rats underwent the Y-maze, Barnes maze, and passive avoidance tests and their brains were subjected to histologic studies. The OP group showed VaD-associated memory deficits, hippocampal neuronal death, and microglial activation; however, the PFL-treated groups showed significant attenuations in all of the above parameters. Using lipopolysaccharide (LPS)-stimulated BV-2 cells, a murine microglial cell line, we measured PFL-mediated changes on the production of nitric oxide (NO), TNF-α, and IL-6, and the activities of their upstream MAP kinases (MAPKs)/NFκB/inducible NO synthase (iNOS). The LPS-induced upregulations of NO, TNF-α, and IL-6 production and MAPKs/NFκB/iNOS activities were globally and significantly reversed by 12-h pretreatment of PFL. This suggests that PFL can counteract VaD-associated structural and functional deterioration through the attenuation of neuroinflammation.

The Changes in Epidemiology of Imipenem-Resistant Acinetobacter baumannii Bacteremia in a Pediatric Intensive Care Unit for 17 Years.

BACKGROUND: Acinetobacter baumannii infections cause high morbidity and mortality in intensive care unit (ICU) patients. However, there are limited data on the changes of long-term epidemiology of imipenem resistance in A. baumannii bacteremia among pediatric ICU (PICU) patients. METHODS: A retrospective review was performed on patients with A. baumannii bacteremia in PICU of a tertiary teaching hospital from 2000 to 2016. Antimicrobial susceptibility tests, multilocus sequence typing (MLST), and polymerase chain reaction for antimicrobial resistance genes were performed for available isolates. RESULTS: A. baumannii bacteremia occurred in 27 patients; imipenem-sensitive A. baumannii (ISAB, n = 10, 37%) and imipenem-resistant A. baumannii (IRAB, n = 17, 63%). There was a clear shift in the antibiogram of A. baumannii during the study period. From 2000 to 2003, all isolates were ISAB (n = 6). From 2005 to 2008, both IRAB (n = 5) and ISAB (n = 4) were isolated. However, from 2009, all isolates were IRAB (n = 12). Ten isolates were available for additional test and confirmed as IRAB. MLST analysis showed that among 10 isolates, sequence type 138 was predominant (n = 7). All 10 isolates were positive for OXA-23-like and OXA-51-like carbapenemase. Of 27 bacteremia patients, 11 were male (41%), the median age at bacteremia onset was 5.2 years (range, 0-18.6 years). In 33% (9/27) of patients, A. baumannii was isolated from tracheal aspirate prior to development of bacteremia (median, 8 days; range, 5-124 days). The overall case-fatality rate was 63% (17/27) within 28 days. There was no statistical difference in the case fatality rate between ISAB and IRAB groups (50% vs. 71%; P = 0.422). CONCLUSION: IRAB bacteremia causes serious threat in patients in PICU. Proactive infection control measures and antimicrobial stewardship are crucial for managing IRAB infection in PICU.

Immune-Enhancing Effect of Sargassum horneri on Cyclophosphamide-Induced Immunosuppression in BALB/c Mice and Primary Cultured Splenocytes.

Sargassum horneri (SH) is a seaweed that has several features that benefit health. In this study, we investigated the immune-enhancing effect of SH, focusing on the role of spleen-mediated immune functions. Chromatographic analysis of SH identified six types of monosaccharide contents, including mannose, rhamnose glucose, galactose xylose and fucose. SH increased cell proliferation of primary cultured naïve splenocytes treated with or without cyclophosphamide (CPA), an immunosuppression agent. SH also reversed the CPA-induced decrease in Th1 cytokines. In vivo investigation revealed that SH administration can increase the tissue weight of major immune organs, such as the spleen and thymus. A similar effect was observed in CPA-injected immunosuppressed BALB/c mice. SH treatment increased the weight of the spleen and thymus, blood immune cell count and Th1 cytokine expression. Additionally, the YAC-1-targeting activities of natural killer cells, which are important in innate immunity, were upregulated upon SH treatment. Overall, our study demonstrates the immune-enhancing effect of SH, suggesting its potential as a medicinal or therapeutic agent for pathologic conditions involving immunosuppression.

Erratum: Correction of Text in the Article "Pediatric Emergency Department Utilization and Coronavirus Disease in Daegu, Korea".

This corrects the article on p. e11 in vol. 36, PMID: 33398945.

Pediatric Emergency Department Utilization and Coronavirus Disease in Daegu, Korea.

BACKGROUND: Limited data exist on children's utilization of the emergency department (ED) in the ongoing coronavirus disease 2019 (COVID-19) pandemic. Thus, we aimed to examine ED utilization among pediatric patients and the impact of COVID-19 in one large city affected by the outbreak. METHODS: This retrospective study included data from six EDs in Daegu, Korea. We compared the demographic and clinical data of patients presenting to the ED during the COVID-19 pandemic (February 1st-June 30th 2020) with those of patients who visited the ED in this period during 2018 and 2019. RESULTS: Fewer patients, particularly children visited the EDs during the study period in 2020 than those in the previous (2018/2019) year period: the number of adult patient decreased by 46.4% and children by 76.9%. Although the number of patients increased from the lowest point of the decrease in March 2020, the number of pediatric patients visiting the ED remained less than half (45.2%) in June 2020 compared with that of previous years. The proportion of patients with severe conditions increased in adults, infants, and school-aged children, and consequently resulted in increased ambulance use and higher hospitalization rates. Fewer infants and young children but more school-aged children visited the ED with febrile illnesses in 2020 than in 2018/2019. CONCLUSION: The COVID-19 pandemic has led to a substantial decrease in pediatric ED utilization. These findings can help reallocate human and material resources in the EDs during infectious disease outbreaks.

Therapeutic Drug Level Monitoring of Teicoplanin in Korean Pediatric Patients with Normal versus Impaired Renal Function.

BACKGROUND: Teicoplanin is used to treat serious gram-positive infections. Optimal teicoplanin trough levels are considered to be ≥ 10 µg/mL. Despite its wide use in various clinical settings, data on teicoplanin trough level in pediatric patients are limited. Therefore, the aim of this study was to investigate the therapeutic drug level monitoring of teicoplanin in Korean pediatric patients, including those with impaired renal function. METHODS: A retrospective study was performed in pediatric patients (age ≤ 18 years old) who received teicoplanin from September 2014 to April 2018. The regimen included a loading dose of 10 mg/kg/dose at 12 hours' interval three times in a row, and a maintenance dose of 10 mg/kg/dose commenced at 24 hours of interval after the loading dose, with a maximum of 400 mg/dose, respectively. The first therapeutic drug levels were measured. Distribution and characteristics of trough levels in patients with decreased renal function and those with bacteremia were also assessed. RESULTS: A total of 187 trough levels were collected from 143 patients. Hematologic and oncologic diseases were the most common underlying diseases (83.2%, n = 119). One hundred eighty trough levels were first measured, and their median value was 16.2 µg/mL (range, 2.3-100 µg/mL) and the median interval between initial teicoplanin injection and 1st trough level was 96.5 hours (range 47.6-179.3 hours). Lower steady-state levels were observed in younger age group (median, 13.5 vs. 18.0 µg/mL, P = 0.038). Median trough levels were higher in patients with decreased renal functions (P < 0.001). In addition, among eight with gram-positive bacteremia, seven of them had a favorable outcome. CONCLUSION: This study provides additive information on trough level monitoring of teicoplanin in children with impaired renal function and treatment effect in patients with gram-positive bacteremia. Careful monitoring for steady state trough levels of teicoplanin is warranted.

Verbascoside-Rich Abeliophyllum distichum Nakai Leaf Extracts Prevent LPS-Induced Preterm Birth Through Inhibiting the Expression of Proinflammatory Cytokines from Macrophages and the Cell Death of Trophoblasts Induced by TNF-α.

Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1ß, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.

Differences in the Clinical Significance of Antinuclear Antibodies According to Titers and Patterns in Children.

This study aimed to evaluate the differences in the clinical significance of antinuclear antibody (ANA) according to their titers and patterns in the diagnosis of systemic autoimmune diseases (AiD) in pediatric patients. Of the 2442 children who had undergone an ANA test, 473 (19.4%) were positive for ANA, of whom 33 (7.0%) were diagnosed with significant AiD. The positive predictive value (PPV) for significant AiD was considerably high on application of an ANA titer of ≥1:640, and the PPV of a dense fine speckled (DFS) pattern was significantly lower compared with those of speckled and homogenous patterns. The diagnostic value of ANA positivity for AiD is limited, and the clinical significance of the DFS pattern is relatively lower compared with that of other patterns, such as homogenous and speckled patterns, in children. It is necessary to approach the significance of ANA in children individually depending on titers and patterns.

Rubus fruticosus leaf extract inhibits vascular dementia-induced memory impairment and neuronal loss by attenuating neuroinflammation.

Vascular dementia (VaD) is characterized by progressive memory impairment, which is associated with microglia-mediated neuroinflammation. Polyphenol-rich natural plants, which possess anti-inflammatory activities, have attracted scientific interest worldwide. This study investigated whether Rubus fruticosus leaf extract (RFLE) can attenuate VaD. Sprague-Dawley rats were separated into five groups: SO, sham-operated and treated with vehicle; OP, operated and treated with vehicle; RFLE-L, operated and treated with low dose (30 mg/kg) of RFLE; RFLE-M, operated and treated with medium dose (60 mg/kg) of RFLE; and RFLE-H, operated and treated with high dose (90 mg/kg) of RFLE. Bilateral common carotid artery and hypotension were used as a modeling procedure, and the RFLE were intraorally administered for 5 days (preoperative 2 and postoperative 3 days). The rats then underwent memory tests including the novel object recognition, Y-maze, Barnes maze, and passive avoidance tests, and neuronal viability and neuroinflammation were quantified in their hippocampi. The results showed that the OP group exhibited VaD-associated memory deficits, neuronal death, and microglial activation in hippocampi, while the RFLE-treated groups showed significant attenuation in all above parameters. Next, using BV-2 microglial cells challenged with lipopolysaccharide (LPS), we evaluated the effects of RFLE in dynamics of proinflammatory mediators and the upstream signaling pathway. RFLE pretreatment significantly inhibited the LPS-induced release of nitric oxide, TNF-α, and IL-6 and upregulation of the MAPKs/NF-κB/iNOS pathway. Collectively, we suggest that RFLE can attenuate the histologic alterations and memory deficits accompanied by VaD, and these roles are, partly due to the attenuation of microglial activation.

Anti-Atopic Activities of Sargassum horneri Hot Water Extracts in 2,4-Dinitrochlorobezene-Induced Mouse Models.

Atopic dermatitis (AD) is a chronic inflammation associated with skin hypersensitivity caused by environmental factors. The objent of this study was to assess the hot water extracts of Sargassum horneri (SHHWE) on AD. AD was induced by spreading 2,4-dinitrochlorobenzene (DNCB) on the BALB/c mice. The efficacy of SHHWE was tested by observing the immunoglobulin E (IgE), cytokine, skin clinical severity score and cytokine secretions in concanavalin A (Con A)-stimulated splenocytes. The levels of interleukine (IL)-4, IL-5 and IgE, the pro-inflammatory cytokines that are closely related, were notably suppressed in a does-dependent manner by SHHWE, whereas the level of interferon γ (IFN-γ), the atopy-related Th1 cytokine inhibiting the production of Th2 cytokines, was increased. Therefore, these results show that SHHWE has a potent anti-inhibitory effect on AD and is highly valuable for cosmetic development.

Microbiologic Epidemiology of Early-onset Sepsis in Neonates Born at ≥35 0/7 Weeks' Gestation in Korea During 2009-2018.

BACKGROUND: Sepsis within the first 3 days of life remains a leading cause of neonatal mortality and morbidity. However, few studies have addressed the epidemiology of sepsis in late preterm and term neonates, particularly in Asia. We aimed to estimate the epidemiology of early-onset sepsis (EOS) in neonates born at ≥35 0/7 weeks' gestation in Korea. METHODS: A retrospective study was conducted in neonates with proven EOS born at ≥35 0/7 weeks' gestation from 2009 to 2018 at seven university hospitals. EOS was defined as identifying bacteria from a blood culture within 72 hours after birth. RESULTS: A total of 51 neonates (0.36/1,000 live births) with EOS were identified. The median duration from birth to the first positive blood culture collection was 17 hours (range, 0.2-63.9). Among the 51 neonates, 32 (63%) patients were born by vaginal delivery. The median Apgar score was 8 (range, 2-9) at 1 minute and 9 (range, 4-10) at 5 minutes. The most common pathogen was group B Streptococcus (n = 21; 41.2%), followed by coagulase-negative staphylococci (n = 7; 13.7%) and Staphylococcus aureus (n = 5, 9.8%). Forty-six (90.2%) neonates were treated with antibiotics on the first day of symptom onset, and 34 (73.9%) neonates received susceptible antibiotics. The overall 14-day case-fatality rate was 11.8%. CONCLUSION: This is the first multicenter study on the epidemiology of proven EOS in neonates born at ≥35 0/7 weeks' gestation and found that group B Streptococcus was the most common pathogen in Korea.

Genome-wide association study and fine-mapping on Korean biobank to discover renal trait-associated variants.

Background: Chronic kidney disease is a significant health burden worldwide, with increasing incidence. Although several genome-wide association studies (GWAS) have investigated single nucleotide polymorphisms (SNP) associated with kidney trait, most studies were focused on European ancestry. Methods: We utilized clinical and genetic information collected from the Korean Genome and Epidemiology Study (KoGES). Results: More than five million SNPs from 58,406 participants were analyzed. After meta-GWAS, 1,360 loci associated with estimated glomerular filtration rate (eGFR) at a genome-wide significant level (p = 5 × 10-8) were identified. Among them, 399 loci were validated with at least one other biomarker (blood urea nitrogen [BUN] or eGFRcysC) and 149 loci were validated using both markers. Among them, 18 SNPs (nine known ones and nine novel ones) with 20 putative genes were found. The aggregated effect of genes estimated by MAGMA gene analysis showed that these significant genes were enriched in kidney-associated pathways, with the kidney and liver being the most enriched tissues. Conclusion: In this study, we conducted GWAS for more than 50,000 Korean individuals and identified several variants associated with kidney traits, including eGFR, BUN, and eGFRcysC. We also investigated functions of relevant genes using computational methods to define putative causal variants.

Inhibitory effect of ethanolic extract of Abeliophyllum distichum leaf on 3T3-L1 adipocyte differentiation.

BACKGROUND/OBJECTIVES: Abeliophyllum distichum is a plant endemic to Korea, containing several beneficial natural compounds. This study investigated the effect of A. distichum leaf extract (ALE) on adipocyte differentiation. MATERIALS/METHODS: The cytotoxic effect of ALE was analyzed using cell viability assay. 3T3-L1 preadipocytes were differentiated using induction media in the presence or absence of ALE. Lipid accumulation was confirmed using Oil Red O staining. The mRNA expression of adipogenic markers was measured using RT-PCR, and the protein expressions of mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor gamma (PPARγ) were measured using western blot. Cell proliferation was measured by calculating the incorporation of Bromodeoxyuridine (BrdU) into DNA. RESULTS: ALE reduced lipid accumulation in differentiated adipocytes, as indicated by Oil Red O staining and triglyceride assays. Treatment with ALE decreased the gene expression of adipogenic markers such as Pparγ, CCAAT/enhancer binding protein alpha (C/ebpα), lipoprotein lipase, adipocyte protein-2, acetyl-CoA carboxylase, and fatty acid synthase. Also, the protein expression of PPARγ was reduced by ALE. Treating the cells with ALE at different time points revealed that the inhibitory effect of ALE on adipogenesis is higher in the early period treatment than in the terminal period. Furthermore, ALE inhibited adipocyte differentiation by reducing the early phase of adipogenesis and mitotic clonal expansion. This was indicated by the lower number of cells in the Synthesis phase of the cell cycle (labeled using BrdU assay) and a decrease in the expression of early adipogenic transcription factors such as C/ebpß and C/ebpδ. ALE suppressed the phosphorylation of MAPK, confirming that the effect of ALE was through the suppression of early phase of adipogenesis. CONCLUSIONS: Altogether, the results of the present study revealed that ALE inhibits lipid accumulation and may be a potential agent for managing obesity.

Development of Spinal Tuberculosis in an Adolescent With Crohn's Disease After Infliximab Therapy: A Case Report With Literature Review.

INTRODUCTION: Tuberculosis (TB) spondylitis, also known as Pott's disease, is a severe form of extrapulmonary TB. Infliximab treatment for Crohn's disease (CD) patients increases the risk of TB, and is likely to increase the risk of TB spondylitis as well. CASE PRESENTATION: We report a rare case of TB spondylitis development in a 16-year-old female with CD. She had a close household contact of active pulmonary TB and received contact investigation. She was diagnosed with latent TB 1 month before the diagnosis of CD, and had started a latent TB treatment regimen with isoniazid for 9 months. At 5 months from the start of latent TB treatment, infliximab was started. Approximately 1 year after infliximab treatment, her infusion interval was shortened from every 8 weeks to every 4 weeks owing to secondary loss of response due to nonimmunogenic pharmacokinetic failure. One month later, miliary TB developed and infliximab was stopped. She received a miliary TB treatment regimen for 6 months, curing the disease. Three months later, spinal TB was incidentally detected on abdominal computed tomography. She received a TB treatment regimen for 12 months, curing spinal TB. Currently, she is receiving vedolizumab to treat CD and is in clinical remission. Although this patient has sufficiently been treated at each stage of TB development, particularly for latent TB and miliary TB, TB spondylitis still developed. CONCLUSION: Considering that TB spondylitis developed despite sufficient treatment at each stage, pediatric gastroenterologists should stay cautious when using anti-tumor necrosis factor agents in patients with inflammatory bowel disease with a history of latent TB.