The role of rapid syndromic diagnostic testing of gastrointestinal pathogens as a clinical decision support tool in a pediatric emergency department.

PURPOSE: This study aimed to investigate the role of rapid syndromic diagnostic testing of gastrointestinal pathogens as a clinical decision support tool in a pediatric emergency department (ED) by comparing clinical decision and patient outcome parameters pre- and post-implementation. METHODS: This was a big data analytical study of children < 18 years old without any underlying diseases, that visited the ED with acute moderate to severe diarrhea during a 34-month period from 2018 to 2022 using Seoul St. Mary's hospital's healthcare corporate data warehouse to retrieve demographic, clinical, and laboratory parameters. Outcome measures pre- and post-implementation of a rapid syndromic multiplex gastrointestinal panel (GI panel) were compared. RESULTS: A total of 4,184 patients' data were included in the analyses. Broad spectrum antibiotics were prescribed at a significantly lower rate to patients presenting with acute infectious diarrhea at discharge from the ED (9.9% vs 15.8%, P < 0.001) as well as upon admission (52.2% vs 66.0%, P < 0.001) during the post-implementation period compared to the pre-implementation period. Although the duration of ED stay was found to be significantly longer (6.5 vs 5.5 h, P < 0.0001), the rate of ED revisit due to persistent or aggravated symptoms was significantly lower (Δ in intercept, ß = -0.027; SE = 0.013; P = 0.041), and the admission rate at follow up after being discharged from the ED shown to be significantly lower during the post-implementation period compared to the pre-implementation period (0.8% vs. 2.1%, P = 0.001, respectively). No significant difference in disease progression was observed (P = 1.000). CONCLUSION: Using the GI panel in the ED was shown to decrease broad spectrum antibiotic prescribing practices and reduce revisits or admission at follow up by aiding clinical decisions and improving patient outcome.

Expert Consensus on the Structure, Role, and Procedures of the Korea Expert Committee on Immunization Practices.

BACKGROUND: The Korea Expert Committee on Immunization Practices (KECIP) is a key advisory body the government to develop guidelines and provide technical advisory activities on immunization policies in Korea. A recent policy study, inspired by global best practices, aims to enhance KECIP's functionality for providing timely and transparent recommendations in the face of evolving vaccine science and emerging infectious diseases like COVID-19. METHODS: This study reviewed the current status of KECIP and collected expert opinions through surveys and consultations. Among the 40 panel members who were surveyed, 19 responded to a questionnaire specifically designed to assess the potential areas of improvement within KECIP. RESULTS: The majority of respondents favored maintaining the current member count and emphasized the need for a subcommittee. Opinions varied on issues such as the length of KECIP's term, the representation of vaccine manufacturers' perspectives, and the chairperson's role. However, there was a consensus on the importance of expertise, transparency, and fair proceedings within the committee. CONCLUSION: This study underscores the pivotal role of KECIP in shaping national immunization policies, emphasizing the necessity for informed guidance amidst evolving vaccine science and emerging infectious diseases. Furthermore, it stressed the importance of enhancing KECIP's capacity to effectively address evolving public health challenges and maintain successful immunization programs in South Korea.

A booster administration of the OKA/SK strain causes fatal disseminated varicella in an immunocompetent child.

Live varicella vaccines are known to provide robust immunity against varicella zoster virus (VZV) infections. However, problems with viral attenuation have led to pathogenic VZV vaccine strains causing varicella-like rash and herpes zoster in immunocompetent children after immunization. We report the first fatal case of VZV infection caused by OKA/SK strain contained in the vaccine administrated as a booster shot in an immunocompetent child, which has been independently developed from any currently available varicella vaccines that are OKA strain or MAV/06 strain based. The patient died due to sudden pulmonary alveolar hemorrhage as a secondary complication of VZV pneumonitis. Sequencing of the four SNPs unique to the OKA/SK strain (SNP loci 14 035T; 32 626C; 58 777G; 70 319G) enabled discrimination of the strain responsible for the disseminated infection. OKA/SK strain does not have any SNPs in ORF62 postulated to be responsible for the attenuation of varicella vaccines which have been safely and effectively used world-wide or locally, and exclusively enriches a virulent factor in ORF31 identified in parental OKA strain, thus possibly resulting in disseminated VZV infection leading to mortality. Therefore, actions need to be taken to prevent vaccine related morbidity and mortality in children.

In vitro modeling of liver fibrosis with 3D co-culture system using a novel human hepatic stellate cell line.

Hepatic stellate cells (HSCs) play an important role in liver fibrosis; however, owing to the heterogeneity and limited supply of primary HSCs, the development of in vitro liver fibrosis models has been impeded. In this study, we established and characterized a novel human HSC line (LSC-1), and applied it to various types of three-dimensional (3D) co-culture systems with differentiated HepaRG cells. Furthermore, we compared LSC-1 with a commercially available HSC line on conventional monolayer culture. LSC-1 exhibited an overall upregulation of the expression of fibrogenic genes along with increased levels of matrix and adhesion proteins, suggesting a myofibroblast-like or transdifferentiated state. However, activated states reverted to a quiescent-like phenotype when cultured in different 3D culture formats with a relatively soft microenvironment. Additionally, LSC-1 exerted an overall positive effect on co-cultured differentiated HepaRG, which significantly increased hepatic functionality upon long-term cultivation compared with that achieved with other HSC line. In 3D spheroid culture, LSC-1 exhibited enhanced responsiveness to transforming growth factor beta 1 exposure that is caused by a different matrix-related protein expression mechanism. Therefore, the LSC-1 line developed in this study provides a reliable candidate model that can be used to address unmet needs, such as development of antifibrotic therapies.

Molecular epidemiology of Acinetobacter baumannii complex causing invasive infections in Korean children during 2001-2020.

BACKGROUND: Acinetobacter baumannii (AB) has emerged as one of the most problematic pathogens affecting critically ill patients. This study aimed to investigate the longitudinal epidemiology of AB causing invasive diseases in children. METHODS: Acinetobacter spp. cultured from sterile body fluids and identified as Acinetobacter calcoaceticus-baumannii (ACB) complexes by automated systems from children aged below 19 years old were prospectively collected during 2001-2020. The discriminative partial sequence of rpoB gene was sequenced to identify the species, and sequence types (STs) were determined. Temporal changes in antimicrobial susceptibilities and STs were analyzed. RESULTS: In total, 108 non-duplicate ACB isolates were obtained from patients with invasive infections. The median age was 1.4 (interquartile range, 0.1-7.9) years, and 60.2% (n = 65) were male. Acinetobacter baumannii comprised 55.6% (n = 60) of the isolates, and the 30-day mortality was higher in patients with isolated AB than in those with non-baumannii Acinetobacter spp. (46.7% vs. 8.3%, P < 0.001). After 2010, complete genotype replacement was observed from non-CC92 genotypes to only CC92 genotypes. Carbapenem resistance rates were highest in AB CC92 (94.2%), followed by AB non-CC92 (12.5%) and non-baumannii Acinetobacter spp. (2.1%). During 2014-2017, which included clustered cases of invasive ST395, colistin resistance increased to 62.5% (n = 10/16), showing a mortality rate of 88% during this period. CONCLUSION: Complete genotype replacement of non-CC92 with CC92 genotypes was observed. AB CC92 was extensively drug-resistant, and pandrug resistance was observed depending on the ST, warranting careful monitoring.

A fatal case of pneumonia caused by Thermothelomycesthermophila.

Thermothelomyces thermophila (formerly Myceliophthora thermophila) is usually found in soil and specifically compost as an environmental dematiaceous fungus. Here, we report the first case of invasive pulmonary infection caused by T. thermophila in a pediatric patient with acute lymphoblastic leukemia. T. thermophila was serially cultured from bronchoalveolar lavage (BAL) fluid and sputum samples obtained from this patient with respiratory symptoms. The patient received antifungal treatment with liposomal amphotericin B (160 mg daily) and itraconazole (200 mg daily) combination therapy, but she died. By the antifungal susceptibility testing, low minimum inhibitory concentrations (MIC) were observed for itraconazole (MIC 0.06 µg/mL), voriconazole (MIC 0.12 µg/mL), and posaconazole (MIC 0.03 µg/mL) but high MIC was observed with amphotericin B (MIC 4.0 µg/mL). Since T. thermophila is usually found in the environment, it can be considered as a contaminant and may cause difficulties in diagnosis. Therefore, it is necessary to confirm the potential of pathogen through repeated culture and to conduct an antifungal susceptibility testing to find a suitable antifungal agent.

Twenty-Five Year Trend Change in the Etiology of Pediatric Invasive Bacterial Infections in Korea, 1996-2020.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI). METHODS: A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed. RESULTS: A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (rs = -0.430, P = 0.036), H. influenzae (rs = -0.922, P < 0.001), while trend toward an increase in the relative proportion of S. aureus (rs = 0.850, P < 0.001), S. agalactiae (rs = 0.615, P = 0.001), and S. pyogenes (rs = 0.554, P = 0.005). CONCLUSION: In the proportion of IBIs over a 24-year period between 1996 and 2019, we observed a decreasing trend for S. pneumoniae and H. influenzae and an increasing trend for S. aureus, S. agalactiae, and S. pyogenes in children > 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era.

One-year changes in the pediatric emergency department caused by prolonged coronavirus disease 2019 pandemic.

BACKGROUND: With the coronavirus disease 2019 (COVID-19) pandemic lasting for more than a year, it is imperative to identify the associated changes in the use of emergency medical care for efficient operation of the pediatric emergency department (PED). This study was conducted to determine the long-term impact of the COVID-19 pandemic on patterns of PED visits. METHODS: This is a retrospective observational study of visits to the PED of six hospitals, between January 1, 2017, and December 31, 2020. We compared changes in the characteristics of patients before and during the COVID-19 pandemic. RESULTS: A total of 245 022 visits were included in this analysis. After the first case of COVID-19 was reported in Korea, we observed a significant decrease (54.2%) in PED visits compared with the annual average number of visits in the previous 3 years. Since then, the weekly number of PED visits decreased by 11.9 person/week (95% CI: -15.3--8.4, P < 0.001), which included an increase of 0.21% (95% CI: 0.15%-0.26%, P < 0.001) per week in high acuity patients. From 2017 to 2020, the proportion of infectious respiratory diseases by year was 25.9%, 27.0%, 28.6%, and 16.3%, respectively, demonstrating a significant decrease in 2020 (P < 0.001). CONCLUSIONS: During the COVID-19 pandemic, the number of patient visits to PEDs continues to decline, especially among those with infectious diseases. However, the disease severity of patients has gradually increased. There has been a change in the characteristics of visits to PEDs after COVID-19 which will require an appropriate response from a long-term perspective.

Changes in the Incidence of Intussusception and Infectious Diseases After the COVID-19 Pandemic in Korea.

BACKGROUND: Intussusception refers to the invagination of a part of the intestine into itself. The exact cause for this condition is unknown in most cases. The active implementation of coronavirus disease 2019 (COVID-19) infection control guidelines has reduced the spread of COVID-19 and the incidence of other infectious diseases in children. The current study aimed to identify changes in pediatric intussusception and infectious diseases after the implementation of infection control guidelines and confirm the association between intussusception and contagious diseases. METHODS: We analyzed the electronic medical records of pediatric patients diagnosed with intussusception from seven hospitals in Korea between January 2017 and December 2020. We used open data from the Korea Disease Control and Prevention Agency to investigate changes in infectious diseases over the same period. RESULTS: Altogether, we evaluated 390 children with intussusception. There was a statistically significant decrease in the incidence of monthly visits with intussusception in the COVID-19 period group (9.0 vs. 3.5, P < 0.001). When the monthly incidence of infectious diseases was compared between the pre-COVID-19 and the COVID-19 periods, a statistically significant decrease in respiratory viruses (7979.0 vs. 815.2, P < 0.001), enterovirus infection (262.2 vs. 6.6, P < 0.001), and viral enteritis (916.2 vs. 197.8, P < 0.001) were confirmed in the COVID-19 period. Through interrupted time series analysis, it was confirmed that the incidence of intussusception and viral infectious diseases have drastically decreased since March 2020, when COVID-19 infection control guidelines were actively implemented. CONCLUSION: We confirmed that implementing infection control guidelines during the COVID-19 pandemic resulted in a decrease in intussusception and viral infectious diseases. Through this result, it was possible to indirectly confirm the existing hypothesis that viral infections play a significant role in the pathophysiologic mechanism of intussusception.

The Impact of the Coronavirus Disease-2019 Pandemic on Childhood Obesity and Vitamin D Status.

BACKGROUND: The risk of weight gain as a consequence of school closure in children during the coronavirus disease-2019 (COVID-19) pandemic has been recognized. This study was performed to investigate changes in anthropometric and metabolic parameters in children following a 6-month period of social distancing and school closure due to the pandemic. METHODS: This retrospective cohort study was conducted in school-aged children that were on routine follow-up at the Growth Clinic of Seoul St. Mary's Hospital. Changes in body mass index (BMI) standard deviation scores (z-scores), lipid profiles, and vitamin D levels were investigated. The 1-year period prior to school closure was defined as "pre-COVID-19 period," and the subsequent 6-month period as "COVID-19 period." RESULTS: Overall, 226 children between 4 to 14 years old without comorbidities were assessed. On average, their BMI z-scores increased by 0.219 (95% confidence interval [CI], 0.167-0.271; P < 0.001) in the COVID-19 period compared to the pre-COVID-19 period, and the proportion of overweight or obesity increased from 23.9% in the pre-COVID-19 period to 31.4% in the COVID-19 period. The number of days after school closure (P = 0.004) and being in the normoweight category in the pre-COVID-19 period (P = 0.017) were factors associated with an increased BMI in the COVID-19 period. The mean triglyceride (105.8 mg/dL vs. 88.6 mg/dL, P < 0.001) and low-density lipoprotein-cholesterol (100.2 mg/dL vs. 94.0 mg/dL, P = 0.002) levels were higher, whereas the calcidiol level (18.9 mg/dL vs. 23.8 mg/dL, P < 0.001) was lower in the COVID-19 period compared to the pre-COVID-19 period. CONCLUSION: Within 6 months, increased childhood obesity and vitamin D deficiencies were observed. The duration of school closure was significantly associated with an increased BMI and being normoweight does not exclude the risks for gaining weight.

Stabilization of E2-EPF UCP protein is implicated in hepatitis B virus-associated hepatocellular carcinoma progression.

Hepatitis B virus (HBV) X protein (HBx) is associated with hepatocarcinogenesis. E2-EPF ubiquitin carrier protein (UCP) catalyzes ubiquitination of itself and von Hippel-Lindau protein (pVHL) for degradation and associates with tumor growth and metastasis. However, it remains unknown whether HBx modulates the enzyme activity of UCP and thereby influences hepatocarcinogenesis. Here, we show that UCP is highly expressed in liver tissues of HBx-transgenic mice, but not non-transgenic mice. UCP was more frequently expressed in HBV-positive liver cancers than in HBV-negative liver cancers. HBx binds to UCP specifically and serotype independently, and forms a ternary complex with UCP and pVHL. HBx inhibits self-ubiquitination of UCP, but enhances UCP-mediated pVHL ubiquitination, resulting in stabilization of hypoxia-inducible factor-1α and -2α. HBx and UCP stabilize each other by mutually inhibiting their ubiquitination. HBx promotes cellular proliferation and metastasis via UCP. Our findings suggest that UCP plays a key role in HBV-related hepatocarcinogenesis.

Circulating Respiratory Syncytial Virus Genotypes and Genetic Variability of the G Gene during 2017 and 2018/2019 Seasonal Epidemics Isolated from Children with Lower Respiratory Tract Infections in Daejeon, Korea.

BACKGROUND: Respiratory syncytial virus (RSV) is a major pathogen causing respiratory tract infections in infants and young children. The aim of this study was to confirm the genetic evolution of RSV causing respiratory infections in children at Daejeon in Korea, through G gene analysis of RSV-A and RSV-B strains that were prevalent from 2017 to 2019. METHODS: Pediatric patients admitted for lower respiratory tract infections at The Catholic University of Korea Daejeon St. Mary's Hospital in the 2017 and 2018/2019 RSV seasonal epidemics, who had RSV detected via multiplex polymerase chain reaction (PCR) were included. The nucleic acid containing RSV-RNA isolated from each of the patients' nasal discharge during standard multiplex PCR testing was stored. The G gene was sequenced and phylogenetic analysis was performed using MEGA X program and the genotype was confirmed. RESULTS: A total of 155 specimens including 49 specimens from 2017 and 106 specimens from 2018-2019 were tested. The genotype was confirmed in 18 specimens (RSV-A:RSV-B = 4:14) from 2017 and 8 specimens (RSV-A:RSV-B = 7:1) from 2018/2019. In the phylogenetic analysis, all RSV-A type showed ON1 genotype and RSV-B showed BA9 genotype. CONCLUSION: RSV-B belonging to BA9 in 2017, and RSV-A belonging to ON1 genotype in 2018/2019 was the most prevalent circulating genotypes during the two RSV seasons in Daejeon, Korea.

A liver-specific gene expression panel predicts the differentiation status of in vitro hepatocyte models.

Alternative cell sources, such as three-dimensional organoids and induced pluripotent stem cell-derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell-based therapy has been increasingly needed, and liver transplantation is performed for the treatment for patients with severe end-stage liver disease. Differentiated liver cells and three-dimensional organoids are expected to provide new cell sources for tissue models and revolutionary clinical therapies. However, conventional experimental methods confirming the expression levels of liver-specific lineage markers cannot provide complete information regarding the differentiation status or degree of similarity between liver and differentiated cell sources. Therefore, in this study, to overcome several issues associated with the assessment of differentiated liver cells and organoids, we developed a liver-specific gene expression panel (LiGEP) algorithm that presents the degree of liver similarity as a "percentage." We demonstrated that the percentage calculated using the LiGEP algorithm was correlated with the developmental stages of in vivo liver tissues in mice, suggesting that LiGEP can correctly predict developmental stages. Moreover, three-dimensional cultured HepaRG cells and human pluripotent stem cell-derived hepatocyte-like cells showed liver similarity scores of 59.14% and 32%, respectively, although general liver-specific markers were detected. CONCLUSION: Our study describes a quantitative and predictive model for differentiated samples, particularly liver-specific cells or organoids; and this model can be further expanded to various tissue-specific organoids; our LiGEP can provide useful information and insights regarding the differentiation status of in vitro liver models. (Hepatology 2017;66:1662-1674).

Surveillance of avian influenza viruses in South Korea between 2012 and 2014.

BACKGROUND: National surveillance of avian influenza virus (AIV) in South Korea has been annually conducted for the early detection of AIV and responses to the introduction of highly pathogenic avian influenza (HPAI) virus. In this study, we report on a nationwide surveillance study of AIV in domestic poultry and wild birds in South Korea between 2012 and 2014. METHODS: During the surveillance programs between 2012 and 2014, 141,560 samples were collected. Of these, 102,199 were from poultry farms, 8215 were from LBMs, and 31,146 were from wild bird habitats. The virus isolation was performed by inoculation of embryonated chicken eggs and AIV isolates were detected using hemagglutination assay. For subtying of AIV, the hemagglutinin and neuraminidase genes were confirmed by sequencing. Phylogenetic analysis of the H5 subtypes was performed using 28 H5 AIV isolates. RESULTS: Between 2012 and 2014, a total of 819 AIV were isolated from 141,560 samples. Virus isolation rates for AIV were 0.6, 0.4, 0.1, and 2.7% in wild birds (n = 202), domestic ducks (n = 387), minor poultry (n = 11), and the live bird market (LBM) (n = 219), respectively. In wild birds, various subtypes were found including H1-H7 and H9-H13. The major subtypes were H5 (n = 48, 23.9%: N3 (n = 4) and N8 (n = 44)), H4 (n = 39, 19.4%), and H1 (n = 29, 14.4%). In domestic poultry, mainly ducks, the H5N8 (n = 275, 59.3%), H3 (n = 30, 17.2%), and H6 (n = 53, 11.4%) subtypes were predominantly found. The most frequently detected subtypes in LBM, primarily Korean native chicken, were H9 (n = 169, 77.2%). H3 (n = 10, 4%) and H6 (n = 30, 13.7%) were also isolated in LBM. Overall, the prevalence of AIV was found to be higher between winter and spring and in western parts of South Korea. The unusual high prevalence of the H5 subtype of AIV was due to the large scale outbreak of H5N8 HPAI in wild birds and domestic poultry in 2014. CONCLUSIONS: Enhanced surveillance and application of effective control measures in wild birds and domestic poultry, including LBM, should be implemented to control AI and eradicate HPAI.

Genotype analysis of ORF 62 identifies varicella-zoster virus infections caused by a vaccine strain in children.

This study was performed to differentiate vaccine-type strains from wild-type strains and determine the genotype of varicella-zoster virus (VZV) in 51 Korean children. A sequencing analysis of ORF 62 identified two cases of herpes zoster caused by the vaccine-type virus, without a previous history of varicella, 22 months and 5 months after VZV vaccination. The wild-type strain was identified in the remaining children. A genotype analysis of ORF 22 amino acids revealed genotype J in all children except one. Genotype E was identified in an infant with varicella imported from Egypt.

Predicting augmented renal clearance using estimated glomerular filtration rate in critically-ill children
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AIMS: Measured glomerular filtration rate (mGFR) is often used to identify augmented renal clearance (ARC). However, in the clinical setting, estimated GFR (eGFR) is obtained more quickly and inexpensively. We aimed to determine whether eGFR can identify ARC by evaluating the correlation between the eGFR and vancomycin trough level (VTL). MATERIALS AND METHODS: We retrospectively reviewed the records of patients aged ≤ 18 years who underwent vancomycin therapeutic drug monitoring at our tertiary hospital from July 2009 to June 2014. VTL, serum creatinine concentration, eGFR, and clinical factors affecting VTL were analyzed. RESULTS: Of 101 patients, 76 (75.25%) had a subtherapeutic VTL. Patient age (p = 0.006), the daily vancomycin dose (p = 0.041) and dosing interval (p = 0.006), and eGFR (p < 0.001) affected the VTL. Multivariate analysis showed a significant relationship between eGFR and VTL (adjusted R2, 0.812; p < 0.001). An increased eGFR (odds ratio, 1.002; 95% confidence interval, 1.001 - 1.003; p = 0.001) was a risk factor for a subtherapeutic vancomycin level. The cutoff eGFR value predicting a subtherapeutic vancomycin level was 110.51 mL/min/1.73m2 (area under the curve, 0.753). CONCLUSIONS: The eGFR correlates with the VTL, and the eGFR cutoff value can predict a subtherapeutic vancomycin level. eGFR is a reliable and efficient alternative to mGFR for identifying ARC.
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Deletion of Lkb1 in Renal Tubular Epithelial Cells Leads to CKD by Altering Metabolism.

Renal tubule epithelial cells are high-energy demanding polarized epithelial cells. Liver kinase B1 (LKB1) is a key regulator of polarity, proliferation, and cell metabolism in epithelial cells, but the function of LKB1 in the kidney is unclear. Our unbiased gene expression studies of human control and CKD kidney samples identified lower expression of LKB1 and regulatory proteins in CKD. Mice with distal tubule epithelial-specific Lkb1 deletion (Ksp-Cre/Lkb1(flox/flox)) exhibited progressive kidney disease characterized by flattened dedifferentiated tubule epithelial cells, interstitial matrix accumulation, and dilated cystic-appearing tubules. Expression of epithelial polarity markers ß-catenin and E-cadherin was not altered even at later stages. However, expression levels of key regulators of metabolism, AMP-activated protein kinase (Ampk), peroxisome proliferative activated receptor gamma coactivator 1-α (Ppargc1a), and Ppara, were significantly lower than those in controls and correlated with fibrosis development. Loss of Lkb1 in cultured epithelial cells resulted in energy depletion, apoptosis, less fatty acid oxidation and glycolysis, and a profibrotic phenotype. Treatment of Lkb1-deficient cells with an AMP-activated protein kinase (AMPK) agonist (A769662) or a peroxisome proliferative activated receptor alpha agonist (fenofibrate) restored the fatty oxidation defect and reduced apoptosis. In conclusion, we show that loss of LKB1 in renal tubular epithelial cells has an important role in kidney disease development by influencing intracellular metabolism.

Clinical Characteristics of Severe Histiocytic Necrotizing Lymphadenitis (Kikuchi-Fujimoto Disease) in Children.

OBJECTIVES: To analyze the clinical characteristics of children with Kikuchi-Fujimoto disease focusing on cases with prolonged fever. STUDY DESIGN: This was a retrospective study of children diagnosed with Kikuchi-Fujimoto disease from March 2003 to February 2015 in South Korea. Electronic medical records were searched for clinical and laboratory manifestations. RESULTS: Among 86 histopathologically confirmed cases, the mean age was 13.2 (SD ± 3.1) years, and male to female ratio was 1:1.32. Cervical lymph node enlargement, found in 85 of the patients (99%), was predominantly unilateral in 64 (75%), and involved the cervical lymph node level V in 67 (81%). Fever was present in 76% of the cases, with a median duration of 9 days (IQR 0.25-17.0). Multivariate analysis revealed that a high fever peak ≥ 39.0°C (P = .010) and presentation with ≥ 2 systemic symptoms other than fever (P = .027) were factors that were significantly associated with longer fever duration. As the size of the largest lymph node's short diameter increased, the fever duration increased (P = .015). Leukopenia (P = .022) also had a significant association with a longer fever duration. Patients with sonographic findings of conglomerated enlarged lymph nodes had a longer median duration of fever compared with those with separate enlarged lymph nodes (11 vs 4.5 days, P = .019). CONCLUSIONS: Patients with high fever, more systemic symptoms, leukopenia, and larger lymph nodes with a conglomerated distribution may benefit from early recognition and selective consideration of corticosteroid therapy.