Exploring the Genetic Causes for Postnatal Growth Failure in Children Born Non-Small for Gestational Age.

The most common causes of short stature (SS) in children are familial short stature (FSS) and idiopathic short stature (ISS). Recently, growth plate dysfunction has been recognized as the genetic cause of FSS or ISS. The aim of this study was to investigate monogenic growth failure in patients with ISS and FSS. Targeted exome sequencing was performed in patients categorized as ISS or FSS and the subsequent response to growth hormone (GH) therapy was analyzed. We found 17 genetic causes involving 12 genes (NPR2, IHH, BBS1, COL1A1, COL2A1, TRPS1, MASP1, SPRED1, PTPTN11, ADNP, NADSYN1, and CERT1) and 2 copy number variants. A genetic cause was found in 45.5% and 35.7% of patients with FSS and ISS, respectively. The genetic yield in patients with syndromic and non-syndromic SS was 90% and 23.1%, respectively. In the 11 genetically confirmed patients, a gain in height from -2.6 to -1.3 standard deviations after 2 years of GH treatment was found. The overall diagnostic yield in this study was 41.7%. We identified several genetic causes involving paracrine signaling, the extracellular matrix, and basic intracellular processes. Identification of the causative gene may provide prognostic evidence for the use of GH therapy in non-SGA children.

Clinical Manifestation of Ralstonia mannitolilytica Infection in Pediatric Patients and Epidemiological Investigation of Outbreaks.

BACKGROUND: Ralstonia mannitolilytica is a causative organism of nosocomial infections, particularly associated with contaminated water, and resistant to various antibiotics, including carbapenems. Several clusters of R. mannitolilytica infections appeared in children at our institute from August 2018 to November 2019. METHODS: From March 2009 to March 2023, all patients admitted to Asan Medical Center Children's Hospital in Seoul, Korea, with culture-confirmed R. mannitolilytica and corresponding clinical signs of infection were identified. Epidemiological and environmental investigations were conducted. Polymerase chain reaction (PCR) was performed for the genes of OXA-443 and OXA-444 on R. mannitolilytica isolates. RESULTS: A total of 18 patients with R. mannitolilytica infection were included in this study, with 94.4% (17/18) and 5.6% (1/18) being diagnosed with pneumonia and central line-associated bloodstream infection, respectively. All-cause 30-day mortality rate was 61.1% (11/18), and seven of the fatal cases were caused by R. mannitolilytica infection itself. The resistance rates to meropenem and imipenem werew 94.4% (17/18) and 5.6% (1/18), respectively. Although four out of nine meropenem-resistant R. mannitolilytica isolates had positive PCR results for OXA-443 and OXA-444 genes, there were no significant differences in antimicrobial susceptibility patterns. Environmental sampling identified R. mannitolylica at two sites: a cold-water tap of a water purifier and an exhalation circuit of a patient mechanical ventilator. After implementing and improving adherence to infection control policies, no additional R. mannitolilytica infection cases have been reported since December 2019. CONCLUSION: R. mannitolilytica can cause life-threatening infections with high mortality in fragile pediatric populations. To prevent outbreaks, healthcare workers should be aware of R. mannitolilytica infections and strive to comply with infection control policies.

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.

Prevalence of asthma in preterm and associated risk factors based on prescription data from the Korean National Health Insurance database.

We retrospectively analyzed National Health Insurance claims data (January 2002-December 2018) to determine the asthma prevalence and risk factors among preterm infants born in Korea. Patients with asthma were defined as those with a history of asthma medication prescriptions at least twice per year with International Classification of Diseases, Tenth Edition codes J45 and J46. We enrolled 99,139 preterm infants. The prevalence of asthma among preterm and term infants was 32.7% and 26.9%, 21.2% and 19.1%, 6.7% and 5.9%, 2.0%, and 1.6%, and 2.4% and 1.6% at 2, 5, 10, 15, and 16 years of age, respectively. The relative risk (RR) of asthma in preterm infants was 1.1-fold that in female preterm infants. The RR of asthma medication prescriptions for infants with extreme prematurity was 1.92-fold that of infants with moderate/late pre-term status. Among preterm with bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS) without comorbidities, the RRs for the number of asthma medication prescriptions were 1.34 and 1.06, respectively. This study revealed a higher prevalence of asthma among preterm infants than that in term infants. Male sex, extreme prematurity, BPD, and RDS were identified as risk factors for asthma medication prescriptions in preterm infants.

A Measles Outbreak in a Local Children's Hospital in Korea, 2019.

A measles outbreak with 20 confirmed cases occurred at a local children's hospital in Daejeon from March 28 to April 21, 2019. The index patient was a 7-month-old girl with a recent history of travel to Vietnam. Contact tracing, active surveillance, and post-exposure prophylaxis were conducted by health authorities. Among the 20 patients, 11 (55%) were infants (0-11 months of age), three (15%) were aged 1-3 years, one (5%) was aged 4 years, and five (25%) were adults. Fifteen (75%) patients did not have a history of measles vaccination, and five (25%) had received only one vaccine dose. This study described the importance of prompt application of infection control measures in susceptible environments, including hospitals. Age-appropriate vaccination and providing information on infectious diseases to international travelers and multicultural families in Korea is vital.

Initial empirical antibiotics of non-carbapenems for ESBL-producing E. coli and K. pneumoniae bacteremia in children: a retrospective medical record review.

BACKGROUND: The efficacy of non-carbapenems as an empirical antibiotic for extended-spectrum ß-lactamases (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia in children remains controversial. We compared clinical and microbial outcomes according to the types of empirical antibiotics for treating pediatric patients with ESBL-producing E. coli and K. pneumoniae bacteremia. METHODS: Data from pediatric patients aged ≤ 18 years who were hospitalized with monomicrobial ESBL-producing E. coli or K. pneumoniae bacteremia at Asan Medical Center Children's Hospital, Seoul, Korea between January 2014 and May 2019 were analyzed retrospectively. The impact of empirical therapy was assessed as 30-day all-cause mortality and 2-day microbiological outcomes evaluated by the sterility of blood cultures collected on day 2 after empirical antibiotic administration. Logistic regression analysis was used to control for the effects of confounding variables. RESULTS: A total of 53 patients with bacteremia caused by ESBL-producing E. coli (n = 29) and K. pneumoniae (n = 24) were included in this study; the median age was 3.6 years, and all had underlying comorbidities. As empirical antibiotics, 27 patients were treated with meropenem, and non-carbapenem agents were administered to 26 patients; 84.6% (22/26) were converted to carbapenem antibiotics as the definitive antibiotic by day 2 after empirical antibiotic administration. Overall, the 30-day all-cause mortality of ESBL-producing E. coli and K. pneumoniae bacteremia was 17.0% (9/53). After adjustment, there was no statistically significant association of use of a non-carbapenem agent as an empirical antibiotic with microbiological failure on day 2 and 30-day all-cause mortality [adjusted odds ratio (OR) 1.0; 95% confidence interval (CI) 0.22-4.88, and adjusted OR 0.1; 95% CI 0.01-1.56]. CONCLUSIONS: The empirical use of non-carbapenems might not be a risk factor for mortality and early microbiological outcomes in pediatric patients with ESBL-producing E. coli and K. pneumoniae BSI if early transition to appropriate antimicrobial therapy was possible.

Impact of initial vancomycin pharmacokinetic/pharmacodynamic parameters on the clinical and microbiological outcomes of methicillin-resistant Staphylococcus aureus bacteremia in children.

Optimal vancomycin exposure is important to minimize treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We aimed to analyze the impact of initial vancomycin pharmacokinetic/pharmacodynamic (PK/PD) parameters, including the initial vancomycin C trough and the area under the curve (AUC)/minimal inhibitory concentration (MIC) on the outcomes of pediatric MRSA bacteremia. The study population consisted of hospitalized children aged between 2 months and 18 years with MRSA bacteremia, in whom C trough was measured at least one time within the time period of January 2010 to March 2018. Demographic profiles, underlying diseases, and clinical/microbiological outcomes were abstracted retrospectively. During the study period, 73 cases of MRSA bacteremia occurred in children with a median age of 12.4 months. Severe clinical outcomes leading to intensive care unit stay and/or use of mechanical ventilation occurred in 47.5% (35/73); all-cause 30-day mortality was 9.7% (7/72). The median dosage of vancomycin was 40.0 mg/kg/day. There was a weak linear relationship between C trough and the corresponding AUC/MIC (r = 0.235). ROC curves for achieving an AUC/MIC of 300 suggested that the initial C trough at 10 µg/mL could be used as a cut-off value with a sensitivity of 90.5% and a specificity of 44%. Although persistent bacteremia at 48-72 hours after vancomycin administration was observed more frequently when the initial C trough was < 10 µg/mL and initial AUC/MIC was < 300, initial AUC/MIC < 300 was the only risk factor associated with persistent bacteremia at 48-72 hours (adjusted OR 3.05; 95% CI, 1.07-8.68). Initial C trough and AUC/MIC were not associated with 30-day mortality. Although there was a weak relationship between C trough and AUC/MIC, initial AUC/MIC < 300 could be used as a predictor of persistent MRSA bacteremia at 48-72 hours. Further prospective data on optimal vancomycin dosing are necessary to improve clinical and microbiological outcomes in pediatric MRSA bacteremia.

Korean Music Therapy Students' Experience of Group Music Therapy: A Qualitative Case Study.

The purpose of this qualitative case study is to describe the in-depth experiences of Korean students undergoing group music therapy. Seven students participated in eight consecutive weeks of group music therapy. The researcher collected and triangulated three data resources: individual interview transcripts, participant journals, and audiotaped sessions. The data were analyzed using the case study method and peer debriefing was conducted for trustworthiness. The four emergent themes and six categories were as follows: (1) Discovering one's self (categories: what it means to be "me," learning about self), (2) Inside group music therapy (categories: various responses to experiencing non-directive group, two different sides of experiencing silence, feeling a sense of safety and acceptance, sharing difficult experience with one's own family), (3) Musical experience as a way to explore emotions, and (4) What learned through books became real. The results indicated that the student therapists' experiences were linked to their personal development, unique experience of group music therapy dynamics, musical experience as an emotional container, and clinical development. Finally, it is recommended that cultural adaptations are made by providing both structure and space for Korean students to express themselves.

The relationship of pulmonary artery copper concentrations and genes involved in copper homeostasis in cattle, Swine, and goats.

Liver and pulmonary artery tissue from 5 Angus cross bred steers, 6 goats, and 6 pigs were collected at a commercial abattoir to examine the relationship of pulmonary artery copper (Cu) concentrations and genes involved in copper homeostasis. Liver and pulmonary artery samples were collected at the time of harvest and snap frozen. Liver and pulmonary artery Cu concentrations were determined via flame atomic absorption spectrophotometry and gene expression was determined via real time PCR. Liver Cu concentrations (mg Cu/kg DM±SE) were higher (p<0.01) in cows (396.4±109.1) and goats (181.4±37.0) than in pigs (19.2±3.5). All liver Cu concentrations were within normal ranges and considered adequate for each species. Liver Cu concentration was more variable in cows and goats compared to pig liver Cu concentrations. Pulmonary artery ß-hydroxylproline was higher (p<0.01) in cow and pig than goat. Real Time PCR revealed that goat liver atp7a was positively correlated (r(2) = 0.92; p<0.01) to liver Cu concentrations while cow and pig atp7a was not correlated to liver Cu concentration. In the pig, liver atp7a concentration was positively correlated to atp7b (r(2) = 0.66; p<0.05). Pulmonary artery Cu concentration was highest in cows (14.9±4.7), intermediate in pigs (8.9±3.3), and lowest in goats (3.9±1.1). Goat pulmonary artery Cu concentration was not correlated to ctr1 concentration, however, atp7a concentration was positively correlated with ctr1 (r(2) = 0.90; p<0.01). In cow pulmonary artery, loxl1 concentration was positively correlated to eln mRNA concentration (r(2) = 0.91; p<0.02). Pulmonary artery CTR1 protein concentration was positively correlated to pulmonary artery Cu (r(2) = 0.85; p = 0.03) concentration while negatively correlated to liver Cu (r(2) = -0.79; p<0.04). Pulmonary artery Cu concentration was not correlated to concentration of Cu homeostatic genes in the pig. These data indicate that genes involved in Cu homeostasis (ctr1, atp7A, atp7B, loxl1 and eln) are differently regulated in different species.