1.Stepwise School Opening and an Impact on the Epidemiology of COVID-19 in the Children
Yoonsun YOON ; Kyung-Ran KIM ; Hwanhee PARK ; Soyoung KIM ; Yae-Jean KIM
Journal of Korean Medical Science 2020;35(46):e414-
Background:
Data on severe acute respiratory syndrome coronavirus-2 transmission from a pediatric index patient to others at the school setting are limited. Epidemiological data on pediatric coronavirus disease 2019 (COVID-19) cases after school opening are warranted.
Methods:
We analyzed data of the pediatric patients with COVID-19 collected from the press release of the Korea Centers for Disease Control and Prevention. Information on the school opening delay and re-opening policies were achieved from the press release of the Korean Ministry of Education.
Results:
The school openings were delayed three times in March 2020. Online classes started from April 9, and off-line (in-person) classes started from May 20 to June 8 at four steps in different grades of students. There was no sudden increase in pediatric cases after the school opening, and the proportion of pediatric cases among total confirmed cases in the nation around 7.0%. As of July 31, 44 children from 38 schools and kindergartens were diagnosed with COVID-19 after off-line classes started. More than 13,000 students and staffs were tested; only one additional student was found to be infected in the same classroom. The proportions of pediatric patients without information on infection sources were higher in older age groups than in younger age groups (17.4% vs. 52.4%, P = 0.014). In the younger age group, 78.3% of children were infected by family members, while only 23.8% of adolescents in the older age group were infected by family members (P < 0.001).
Conclusion
Korea had a successful transition from school closure to online and off-line school opening, which did not cause significant school-related outbreak among the pediatric population.
2.A case of FLNA gene mutation with respiratory insufficiency and periventricular heterotopia
Hwanhee PARK ; Min Seung PARK ; Chang Seok KI ; Joongbum CHO ; Jeehun LEE ; Jihyun KIM ; Kangmo AHN
Allergy, Asthma & Respiratory Disease 2019;7(3):158-164
Filamin A is an actin-binding protein and, in humans, is encoded by FLNA gene in the long arm of X chromosome. Filamin A plays a role in the formation of cytoskeleton by crosslinking actin filaments in cytoplasm. FLNA mutations affect cytoskeletal regulatory processes and cellular migrating abnormalities that result in periventricular heterotopia. A 5-month-old girl was hospitalized because of breathing difficulty and was diagnosed as having periventricular heterotopia with laryngomalacia, cricopharyngeal incoordination, pulmonary hypertension, and chronic lung disease. A genetic test was performed to find the cause of periventricular heterotopia, and FLNA gene mutation (c.5998+1G>A) was confirmed for the first time in Korea. After discharge, she developed respiratory failure due to a viral infection at 8 months of her age. In spite of management with mechanical ventilation, she died of pneumothorax and pulmonary hemorrhage. Herein, we report a case of FLNA gene mutation who presented with periventricular nodular heterotopia with respiratory insufficiency.
Actin Cytoskeleton
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Arm
;
Ataxia
;
Cytoplasm
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Cytoskeleton
;
Female
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Filamins
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Hemorrhage
;
Humans
;
Hypertension, Pulmonary
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Infant
;
Korea
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Laryngomalacia
;
Lung Diseases
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Periventricular Nodular Heterotopia
;
Pneumothorax
;
Respiration
;
Respiration, Artificial
;
Respiratory Insufficiency
;
X Chromosome
3.Complications of the Central Nervous System in Pediatric Patients With Common Cold Coronavirus Infection During 2014–2019
Hwanhee PARK ; Kyung-Ran KIM ; Hee Jae HUH ; Yoonsun YOON ; Esther PARK ; Joongbum CHO ; Jiwon LEE ; Jeehun LEE ; Ji Hye KIM ; Yae-Jean KIM
Journal of Korean Medical Science 2023;38(46):e358-
Background:
In pediatric patients, the common cold coronavirus (ccCoV) usually causes mild respiratory illness. There are reports of coronavirus causing central nervous system (CNS) infection in experimental animal models. Some immunocompromised patients have also been reported to have fatal CNS infections with ccCoV. The aim of this study was to investigate the clinical characteristics of CNS complications related to ccCoV infection.
Methods:
From January 2014 to December 2019, a retrospective analysis was performed of medical records from hospitalized patients under 19 years of age whose ccCoV was detected through polymerase chain reaction in respiratory specimens. The CNS complications were defined as clinically diagnosed seizure, meningitis, encephalopathy, and encephalitis.
Results:
A total of 436 samples from 420 patients were detected as ccCoV. Among the 420 patients, 269 patients were immunocompetent and 151 patients were immunocompromised.The most common type of ccCoV was OC43 (52% in immunocompetent, 37% in immunocompromised). CNS complications were observed in 9.4% (41/436). The most common type of CNS complication was the fever-provoked seizure under pre-existing neurologic disease (42% in immunocompetent and 60% in immunocompromised patients).Among patients with CNS complications, two immunocompetent patients required intensive care unit admission due to encephalitis. Three patients without underlying neurological disease started anti-seizure medications for the first time at this admission. There was no death related to ccCoV infection.
Conclusion
ccCoV infection may cause severe clinical manifestations such as CNS complications or neurologic sequelae, even in previously healthy children.
4.Susceptibility to Fosfomycin and Nitrofurantoin of ESBL-PositiveEscherichia coli and Klebsiella pneumoniae Isolated From Urine of Pediatric Patients
Ki-Sup PARK ; Doo Ri KIM ; Jin Yang BAEK ; Areum SHIN ; Kyung-Ran KIM ; Hwanhee PARK ; Sohee SON ; Heeyeon CHO ; Yae-Jean KIM
Journal of Korean Medical Science 2023;38(48):e361-
Background:
Pediatric urinary tract infection (UTI) caused by extended-spectrum β-lactamase (ESBL)-positive gram-negative bacilli (GNB) has limited options for oral antibiotic treatment. The purpose of this study was to investigate the susceptibility of ESBLpositive Escherichia coli and Klebsiella pneumoniae isolates from pediatric urine samples to two oral antibiotics (fosfomycin and nitrofurantoin).
Methods:
From November 2020 to April 2022, ESBL-positive E. coli and K. pneumoniae isolates from urine samples were collected at Samsung Medical Center, Seoul, Korea. Patients over 18 years of age or with malignancy were excluded. For repeated isolates from the same patient, only the first isolate was tested. Minimum inhibitory concentrations (MICs) were measured using agar (fosfomycin) or broth (nitrofurantoin) dilution methods. MIC 50 and MIC 90 were measured for fosfomycin and nitrofurantoin in both E. coli and K. pneumoniae.
Results:
There were 117 isolates from 117 patients, with a median age of 7 months (range, 0.0–18.5 years). Among 117 isolates, 92.3% (108/117) were E. coli and 7.7% (9/117) were K. pneumoniae. Isolates from the pediatric intensive care unit (PICU) and general ward (GW) was 11.1% (13/117) and 88.9% (104/117), respectively. Among 108 E. coli isolates, MIC 50 and MIC 90 for fosfomycin were 0.5 μg/mL and 2 μg/mL, respectively. Fosfomycin susceptibility rate was 97.2% (105/108) with a breakpoint of 128 μg/mL. Fosfomycin susceptibility rate was significantly lower in PICU isolates than in GW isolates (81.8% vs. 99.0%, P = 0.027).For nitrofurantoin, both the MIC 50 and MIC 90 were 16 μg/mL. Nitrofurantoin susceptibility rate was 96.3% (104/108) with a breakpoint of 64 μg/mL based on Clinical and Laboratory Standards Institute guidelines. Among the nine K. pneumoniae isolates, the MIC 50 and MIC 90 for fosfomycin was 2 μg/mL and 32 μg/mL, respectively. MIC 50 and MIC 90 for nitrofurantoin were 64 μg/mL and 128 μg/mL, respectively.
Conclusion
For uncomplicated UTI caused by ESBL-positive GNB in Korean children, treatment with fosfomycin and nitrofurantoin for E. coli infections can be considered as an effective oral therapy option.
5.Epidemiology and Clinical Features of Myocarditis/Pericarditis before the Introduction of mRNA COVID-19 Vaccine in Korean Children:a Multicenter Study
Hwanhee PARK ; Ki Wook YUN ; Kyung-Ran KIM ; Seung Ha SONG ; Bin AHN ; Doo Ri KIM ; Gi Beom KIM ; June HUH ; Eun Hwa CHOI ; Yae-Jean KIM
Journal of Korean Medical Science 2021;36(32):e232-
Background:
Korean health authority plans to vaccinate adolescents against coronavirus disease 2019 (COVID-19) starting high school seniors during the summer vacation of 2021.However, the myocarditis/pericarditis following COVID-19 vaccine has been reported recently in adolescents and young adults. This study was performed to answer the urgent questions about the basic epidemiology and clinical course of myocarditis/pericarditis in hospitalized patients prior to the introduction of COVID-19 vaccines in pediatric population.
Methods:
A retrospective medical record analysis including frequency, clinical characteristics, etiology and outcome of myocarditis/pericarditis was conducted in 17 years and younger patients who were hospitalized in two referral hospitals in Korea between 2010 and 2019.
Results:
Total 142 patients with myocarditis (n = 119) and/or pericarditis (n = 23) were identified. Median age was 5.4 years (interquartile range, 0.6–12.9 years; range, 11 days–17.8 years), and male was 61%. In adolescents aged 12–17 years, the male to female ratio was 3.2. Myocarditis/pericarditis occurred 0.70 per 1,000 in-patients during the study period: 0.96 (< 1 year), 0.50 (1–5 years), 0.67 (6–11 years) and 1.22 (12–17 years) per 1,000 in-patients, respectively. There was an increasing tendency for the annual frequency from 0.34 in 2010 to 1.25 per 1,000 in-patients in 2019 (P = 0.021). Among the 56 (40%) proven pathogens at admission, Mycoplasma pneumoniae (n = 11, 8%) and enterovirus (n = 10, 7%) were most common. Of the 142 patients, 99 (70%) required pediatric intensive care unit care and 10 (7%) received heart transplantation. In addition, 61 patients (61/131, 47%) without heart medication at admission needed heart medication when they were discharged. Eleven (7.7%) patients died, of which five patients were previously healthy. The median age of deceased patients was lower than the survival group (0.8 vs. 6.3 years, P = 0.014).
Conclusion
The frequency of myocarditis/pericarditis was highest among male adolescent in-patients; however, the outcome was favorable in this group without any mortality.
6.Epidemiology and Clinical Features of Myocarditis/Pericarditis before the Introduction of mRNA COVID-19 Vaccine in Korean Children:a Multicenter Study
Hwanhee PARK ; Ki Wook YUN ; Kyung-Ran KIM ; Seung Ha SONG ; Bin AHN ; Doo Ri KIM ; Gi Beom KIM ; June HUH ; Eun Hwa CHOI ; Yae-Jean KIM
Journal of Korean Medical Science 2021;36(32):e232-
Background:
Korean health authority plans to vaccinate adolescents against coronavirus disease 2019 (COVID-19) starting high school seniors during the summer vacation of 2021.However, the myocarditis/pericarditis following COVID-19 vaccine has been reported recently in adolescents and young adults. This study was performed to answer the urgent questions about the basic epidemiology and clinical course of myocarditis/pericarditis in hospitalized patients prior to the introduction of COVID-19 vaccines in pediatric population.
Methods:
A retrospective medical record analysis including frequency, clinical characteristics, etiology and outcome of myocarditis/pericarditis was conducted in 17 years and younger patients who were hospitalized in two referral hospitals in Korea between 2010 and 2019.
Results:
Total 142 patients with myocarditis (n = 119) and/or pericarditis (n = 23) were identified. Median age was 5.4 years (interquartile range, 0.6–12.9 years; range, 11 days–17.8 years), and male was 61%. In adolescents aged 12–17 years, the male to female ratio was 3.2. Myocarditis/pericarditis occurred 0.70 per 1,000 in-patients during the study period: 0.96 (< 1 year), 0.50 (1–5 years), 0.67 (6–11 years) and 1.22 (12–17 years) per 1,000 in-patients, respectively. There was an increasing tendency for the annual frequency from 0.34 in 2010 to 1.25 per 1,000 in-patients in 2019 (P = 0.021). Among the 56 (40%) proven pathogens at admission, Mycoplasma pneumoniae (n = 11, 8%) and enterovirus (n = 10, 7%) were most common. Of the 142 patients, 99 (70%) required pediatric intensive care unit care and 10 (7%) received heart transplantation. In addition, 61 patients (61/131, 47%) without heart medication at admission needed heart medication when they were discharged. Eleven (7.7%) patients died, of which five patients were previously healthy. The median age of deceased patients was lower than the survival group (0.8 vs. 6.3 years, P = 0.014).
Conclusion
The frequency of myocarditis/pericarditis was highest among male adolescent in-patients; however, the outcome was favorable in this group without any mortality.
7.Kerion Celsi Caused by Trichophyton verrucosum Mimicking a Hypervascular Tumor in a Pediatric Patient: A Case Report
Kyung-Ran KIM ; Hwanhee PARK ; Doo Ri KIM ; Yoonsun YOON ; Chiman JEON ; Sanghoon LEE ; So Young LIM ; Ji Hye KIM ; Yae-Jean KIM
Pediatric Infection & Vaccine 2022;29(2):118-123
A dermatophyte is a zoonotic infection that causes infection on the skin, hair, and nails and is transmitted through contact. The species of Microsporum, Trichophyton, and Epidermophyton are the major dermatophytes that infect humans. Tinea capitis is a dermatophyte infection in the scalp, and it may progress to Kerion celsi, including severe redness, swelling, and pus formation. Kerion celsi is sometimes misdiagnosed as a bacterial infection or a tumor. Trichophyton verrucosum is a zoophilic dermatophyte that mainly causes infection in cattle. It can be spread to dairy farmers or ranchers who have frequent contact with infected cattle. We report a pediatric case who received scalp tumor excision and a split-thickness skin graft for extensive and severe inflammatory scalp tumors that occurred after contact with cattle with ringworm. Finally, the patient was diagnosed with Kerion celsi caused by T. verrucosum infection. This was based on the patient’s medical history, clinical manifestations, and histopathologic findings.
8.Immunomodulatory Effect of Epidermal Growth Factor Secreted by Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells on Atopic Dermatitis
Namhee JUNG ; TaeHo KONG ; Yeonsil YU ; Hwanhee PARK ; Eunjoo LEE ; SaeMi YOO ; SongYi BAEK ; Seunghee LEE ; Kyung-Sun KANG
International Journal of Stem Cells 2022;15(3):311-323
Background and Objectives:
Human mesenchymal stem cells (MSCs) are emerging as a treatment for atopic dermatitis (AD), a chronic inflammatory skin disorder that affects a large number of people across the world. Treatment of AD using human umbilical cord blood-derived MSCs (hUCB-MSCs) has recently been studied. However, the mechanism underlying their effect needs to be studied continuously. Thus, the objective of this study was to investigate the immunomodulatory effect of epidermal growth factor (EGF) secreted by hUCB-MSCs on AD.
Methods:
and Results: To explore the mechanism involved in the therapeutic effect of MSCs for AD, a secretome array was performed using culture medium of hUCB-MSCs. Among the list of genes common for epithelium development and skin diseases, we focused on the function of EGF. To elucidate the effect of EGF secreted by hUCB-MSCs, EGF was downregulated in hUCB-MSCs using EGF-targeting small interfering RNA. These cells were then co-cultured with keratinocytes, Th2 cells, and mast cells. Depletion of EGF disrupted immunomodulatory effects of hUCB-MSCs on these AD-related inflammatory cells. In a Dermatophagoides farinae-induced AD mouse model, subcutaneous injection of hUCB-MSCs ameliorated gross scoring, histopathologic damage, and mast cell infiltration. It also significantly reduced levels of inflammatory cytokines including interleukin (IL)-4, tumor necrosis factor (TNF)-α, thymus and activation-regulated chemokine (TARC), and IL-22, as well as IgE levels. These therapeutic effects were significantly attenuated at all evaluation points in mice injected with EGF-depleted hUCB-MSCs.
Conclusions
EGF secreted by hUCB-MSCs can improve AD by regulating inflammatory responses of keratinocytes, Th2 cells, and mast cells.
10.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
Kyung-Ran KIM ; Hyo Jung PARK ; Sun-Young BAEK ; Soo-Han CHOI ; Byung-Kee LEE ; SooJin KIM ; Jong Min KIM ; Ji-Man KANG ; Sun-Ja KIM ; Sae Rom CHOI ; Dongsub KIM ; Joon-sik CHOI ; Yoonsun YOON ; Hwanhee PARK ; Doo Ri KIM ; Areum SHIN ; Seonwoo KIM ; Yae-Jean KIM
Journal of Korean Medical Science 2024;39(21):e172-
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 patientdays, 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.