Clinical Manifestations, Macrolide Resistance, and Treatment Utilization Trends of Mycoplasma pneumoniae Pneumonia in Children and Adolescents in South Korea.

A resurgence of Mycoplasma pneumoniae (MP)-the leading cause of community-acquired bacterial pneumonia, particularly in children-occurred following the COVID-19 pandemic. We aimed to investigate the clinical manifestations, macrolide resistance patterns, and therapeutic approaches related to the MP pneumonia epidemic. Children and adolescents diagnosed with MP pneumonia in September-December 2023 were screened. Clinical data were retrospectively collected from 13 major hospitals using concordant microbiological criteria, including either a positive PCR result or four-fold increase in serological markers. Demographic characteristics, treatment modalities, and clinical outcomes were analyzed. Of the 474 screened patients, 374 (median age: 7.7 [IQR, 5.4-9.6] years; hospitalization rate: 88.6%) met the microbiological confirmation criteria. Most patients experienced fever (98.9%), and lobular/lobar consolidation (59.1%) was the dominant radiological finding. The macrolide resistance rate remained high at 87.0%; corticosteroids were widely used (55.6%) alongside macrolides, despite resistance. Patients with consolidation had prolonged fever (median 8 vs. 7 days, p = 0.020) and higher hospitalization rates (92.3% vs. 83.0%, p = 0.008). Macrolide resistance did not significantly influence radiological outcomes. This study highlights the ongoing challenge of macrolide resistance in MP pneumonia and need for tailored therapeutic approaches. Despite high resistance, macrolides remain commonly prescribed, often concurrently with corticosteroids.

Heightened incidence of adverse events associated with a live attenuated varicella vaccine strain that lacks critical genetic polymorphisms in open reading frame 62.

OBJECTIVES: This study aimed to identify the specific vaccine strain associated with herpes zoster (HZ) in children following a series of diagnosed cases and to explore whether differences in single nucleotide polymorphisms (SNPs) among various vaccine strains are linked to an increased incidence of herpes zoster after vaccination. METHODS: From February 2021 to March 2024, children <12 years old suspected of vaccine-related varicella-like rash or HZ were included. Varicella zoster virus DNA isolated from the patients were sequenced to differentiate vaccine type versus wild-type. 3D protein structures of pORF62 were simulated using open reading frame 62 sequences extracted from whole genome sequencing of vOka, MAV/06, Oka/SK vaccines, and pOka reference. RESULTS: A total of 27 children with a median age of 2.1 (interquartile range, 1.5-3.4) years old presented with vaccine-related varicella-like rash (n = 4/27, 14.8%) or HZ (n = 23/27, 85.2%). One patient with varicella-like rash and 34.8% (n = 8/23) with HZ had disseminated skin involvement. All were immunized with the Oka/SK strain varicella vaccine. Genotyping showed 88.2% (n = 15/17) had SNPs specific to the Oka/SK strain, and two had SNPs considered pOka type contained within the Oka/SK vaccine. Despite accumulations of SNPs in ORF 62 of Oka/SK, the translated amino acid sequence and 3D protein structure were identical to wild-type pOka's pORF62. In vOKA and MAV/06, changes in amino acids occurred at two positions, S628G and R958G, within pORF62. The predicted 3D protein structure of vOka and MAV/06's pORF62 showed that the α helical structure within region I undergoes conformational change, potentially increasing difficulties in interactions with infection-related proteins and thereby decreasing virulence. pORF62 in pOka and Oka/SK exhibited more stable structure complex of the α helical structure. DISCUSSION: Lack of structural alternations in region I of pORF62 due to the absence of critical genetic polymorphisms in open reading frame 62 could be associated with the heightened incidence of adverse events.

Development and validation of enzyme-linked immunosorbent assay for anti-mouse pertussis immunoglobulin G using international reference anti-Bordetella pertussis mouse serum NIBSC 97/642.

Purpose: In this study, an in-house enzyme-linked immunosorbent assay (ELISA) was developed and validated. The titer of ELISA was calculated using the reference line (RFL) method based on the standard curve drawn using the international reference anti-mouse serum NIBSC (National Institute for Biological Standards and Control) 97/642. Materials and Methods: In the development step, signal to noise was depicted to select the buffers that showed the most appropriate ratio. In the validation step, standard range, precision, dilution linearity, and specificity were confirmed, and RFL and parallel line (PLL) methods were compared in precision and dilution linearity. Results: Coating concentration for plate was achieved at 0.1 µg/mL for pertussis toxin (PT), 0.15 µg/mL for filamentous hemagglutinin antigen (FHA), and 0.25 µg/mL for pertactin (PRN). The signal to noise ratio was 22.02 for PT, 14.93 for FHA, and 8.02 for PRN with 0.25% goat serum in phosphate-buffered saline (PBS) as a dilution buffer, and 2% skim milk in PBS as a blocking buffer. Based on the precision results, we assessed the lower limit of quantification by 1, 0.2, and 1.5 EU/mL concentration for PT, FHA, and PRN which met the ICH (International Council for Harmonization) M10 criteria of a 25% accuracy and total error of 40%. In specificity, homologous serum was spiked into heterologous serum and the accuracy met the criteria. There was no difference in the results between RFL and PLL calculations (p-value=0.3207 for PT, 0.7394 for FHA, 0.2109 for PRN). Conclusion: ELISA validated with RFL calculation method in this study is a relatively accurate assay for mouse humoral immunogenicity test.

Antimicrobial resistance genes harbored in invasive Acinetobacter calcoaceticus-baumannii complex isolated from Korean children during the pre-COVID-19 pandemic periods, 2015-2020.

Background: Acinetobacter baumannii (AB) has emerged as one of the most challenging pathogens worldwide, causing invasive infections in the critically ill patients due to their ability to rapidly acquire resistance to antibiotics. This study aimed to analyze antibiotic resistance genes harbored in AB and non-baumannii Acinetobacter calcoaceticus-baumannii (NB-ACB) complex causing invasive diseases in Korean children. Methods: ACB complexes isolated from sterile body fluid of children in three referral hospitals were prospectively collected. Colistin susceptibility was additionally tested via broth microdilution. Whole genome sequencing was performed and antibiotic resistance genes were analyzed. Results: During January 2015 to December 2020, a total of 67 ACB complexes were isolated from sterile body fluid of children in three referral hospitals. The median age of the patients was 0.6 (interquartile range, 0.1-7.2) years old. Among all the isolates, 73.1% (n=49) were confirmed as AB and others as NB-ACB complex by whole genome sequencing. Among the AB isolates, only 22.4% susceptible to carbapenem. In particular, all clonal complex (CC) 92 AB (n=33) showed multi-drug resistance, whereas 31.3% in non-CC92 AB (n=16) (P<0.001). NB-ACB showed 100% susceptibility to all classes of antibiotics except 3rd generation cephalosporin (72.2%). The main mechanism of carbapenem resistance in AB was the bla oxa23 gene with ISAba1 insertion sequence upstream. Presence of pmr gene and/or mutation of lpxA/C gene were not correlated with the phenotype of colistin resistance of ACB. All AB and NB-ACB isolates carried the abe and ade multidrug efflux pumps. Conclusions: In conclusion, monitoring and research for resistome in ACB complex is needed to identify and manage drug-resistant AB, particularly CC92 AB carrying the bla oxa23 gene.

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.

Guidelines for Manufacturing and Application of Organoids: Kidney.

Recent advancements in organoid technology have led to a vigorous movement towards utilizing it as a substitute for animal experiments. Organoid technology offers versatile applications, particularly in toxicity testing of pharmaceuticals or chemical substances. However, for the practical use in toxicity testing, minimal guidance is required to ensure reliability and relevance. This paper aims to provide minimal guidelines for practical uses of kidney organoids derived from human pluripotent stem cells as a toxicity evaluation model in vitro.

Safety assessments of recombinant DTaP vaccines developed in South Korea.

Purpose: Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccines. Materials and Methods: The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments. Results: HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups. Conclusion: There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.

Characterization of Brighton Collaboration criteria for myocarditis and pericarditis following COVID-19 vaccine in Korean adolescents.

BACKGROUND: Vaccines are vital for public health, but concerns about adverse effects, particularly myocarditis and pericarditis linked to COVID-19 vaccines-, persist. This study investigates the application of Brighton Collaboration case definition to national vaccine safety data related to post-COVID-19 vaccine myo/pericarditis, utilizing claims under the Korea National Vaccine Injury Compensation Program (NIVCP). METHODS: This study analyzed 190 medical records of individuals who claimed to have developed myo/pericarditis after receiving the COVID-19 vaccine, as reported to the NVICP between specified dates, categorizing cases based on the Brighton criteria for myocarditis or pericarditis. RESULTS: Between 2021-2022, NVICP received 190 cases meeting the Brighton criteria for myocarditis or pericarditis at levels 1, 2, or 3. Most cases fell into Level 2 (70%), followed by Level 1 (29%), and one at Level 3 (1%), with Level 1 cases showing a higher hospitalization rate (87.3%) and a notable proportion requiring admission to the Intensive Care Unit (25.5%). Chest pain and Troponin-I/T elevation were common findings in Level 1 cases, while Level 2 cases exhibited similar patterns but at a slightly lower frequency. Electrocardiogram and echocardiography findings differed between the two levels. CONCLUSION: The Brighton Collaboration case definition proved valuable for classifying and assessing AEFI data, enhancing our understanding of the potential relationship between myocarditis and the COVID-19 vaccine.

National Level Cross-Sectional Study on Antibiotic Use in Children during the Pre- and Early COVID-19 Eras.

This study aimed to investigate national data for a quantitative evaluation of antibiotic usage in Korean children during the pre- and early COVID-19 period. This was a cross-sectional study from 2016 to 2021 of children <18 years, grouped by age (0, 1, 2-4, 5-11, and 12-17 years) and city/province. Systemic antibiotic prescriptions, days of administration, and population by age and region were collected. Days of therapy (DOT)/1000 pediatric inhabitant per day (PID) was used for antibiotic quantitative monitoring. A total of 257,088,265 antibiotic doses were prescribed to 170,309,944 children during the 6-year period. The highest DOT during the entire study period was observed in the 1-year age group, followed by the 2-4- and 0-year age groups. The highest DOT was observed in 2019, with 72.8 DOT/1000 PID in the 1-year age group, which fell to 34.7 DOT/1000 PID in 2020, however, DOT soon increased at similar rates to that in the pre-COVID-19 period. A higher DOT/1000 PID was observed for third-generation cephalosporins in 58.8% of the regions compared to beta-lactam/beta-lactamase inhibitors. To conclude, reductions in antibiotic use during the early COVID-19 pandemic period were not maintained. Further interventions are needed to decrease antibiotic overuse and misuse.

The effect of minimizing central line days for very low birth weight infants through quality improvement.

Blood culture proven sepsis is associated with increased mortality and morbidity. Given the extended hospitalization of very preterm infants, catheter-related blood stream infections (CRBSIs) play a substantial role in sepsis. The reported incidence of CRBSIs in neonates varies from 3.2 to 21.8 CRBSIs per 1000 catheter line days. Moreover, discrepancies in neonatal practices and potential neglect may lead to the unwarranted prolongation of central lines. This study aims to compare two distinct periods (Pre-QI vs. Post-QI) in relation to the central line insertion rate and duration, as well as blood culture proven sepsis, duration of total parenteral nutrition (TPN), and the progression of feeding. These factors are known to be associated with prolonged hospitalization and increased morbidities. A total of 210 very low birth weight infants (VLBWIs), defined as either less than 32 weeks of gestational age (GA) or weighing less than 1500 g, were admitted to the Neonatal Intensive Care Unit (NICU) at Seoul St. Mary's Hospital, The Catholic University of Korea, between January 2020 and June 2023. Fourteen infants were excluded from the study as they did not survive beyond 1 month of life, and one was excluded due to a congenital anomaly. Consequently, the analysis included 195 VLBWIs. The Quality Improvement (QI) initiative began in January 2022, marking the division into two distinct epochs: the Pre-QI period, encompassing the years 2020 to 2021, and the Post-QI period, spanning from 2022 to 2023. The primary outcome measures included PICC insertion rates, duration, and feeding advancement or feeding-related complications. The hospital outcome measures were also compared between the two periods. A total of 195 VLBWI were included in the analysis. The birth weight was significantly lower in the pre-QI period, with an average of 1023 g compared to 1218 g (P < 0.001). Severe BPD ≥ moderate was significantly lower in the post-QI period (36.2% vs. 53.9%) (P < 0.001) along with shorter mechanical ventilation days (12 ± 29 vs. 22 ± 27) (P = 0.046). The PICC insertion rate was significantly decreased from 95.6% in pre-QI period compared to 55.2% in post-QI period (P < 0.001) along with a notable reduction in blood culture-proven sepsis (25.6% vs. 10.5%, P = 0.008). CRBSI rate was reduced from 1.3 to 1.1 per 1000 catheter days in the post-QI period. Moreover, the time required to achieve full enteral feeding of 100 mL/kg/day was significantly shorter in the post-QI (24 ± 23 vs. 33 ± 25) (P = 0.006). Multivariable logistic regression analysis for sepsis revealed that both birth weight and pre/post QI consistently demonstrated an association with lower sepsis rates in the Post-QI period. QI has the potential to reduce the burden of unnecessary interventions and blood culture proven sepsis rate along with CRBSI rate, thereby, optimizing the better care of very preterm babies.

Comparative Evaluation of Recombinant and Acellular Pertussis Vaccines in a Murine Model.

Since the 2000s, sporadic outbreaks of whooping cough have been reported in advanced countries, where the acellular pertussis vaccination rate is relatively high, and in developing countries. Small-scale whooping cough has also continued in many countries, due in part to the waning of immune protection after childhood vaccination, necessitating the development of an improved pertussis vaccine and vaccination program. Currently, two different production platforms are being actively pursued in Korea; one is based on the aP (acellular pertussis) vaccine purified from B. pertussis containing pertussis toxoid (PT), filamentous hemagglutin (FHA) and pertactin (PRN), and the other is based on the recombinant aP (raP), containing genetically detoxified pertussis toxin ADP-ribosyltransferase subunit 1 (PtxS1), FHA, and PRN domain, expressed and purified from recombinant E. coli. aP components were further combined with diphtheria and tetanus vaccine components as a prototype DTaP vaccine by GC Pharma (GC DTaP vaccine). We evaluated and compared the immunogenicity and the protective efficacy of aP and raP vaccines in an experimental murine challenge model: humoral immunity in serum, IgA secretion in nasal lavage, bacterial clearance after challenge, PTx (pertussis toxin) CHO cell neutralization titer, cytokine secretion in spleen single cell, and tissue resident memory CD4+ T cell (CD4+ TRM cell) in lung tissues. In humoral immunogenicity, GC DTaP vaccines showed high titers for PT and PRN and showed similar patterns in nasal lavage and IL-5 cytokine secretions. The GC DTaP vaccine and the control vaccine showed equivalent results in bacterial clearance after challenge, PTx CHO cell neutralization assay, and CD4+ TRM cell. In contrast, the recombinant raP vaccine exhibited strong antibody responses for FHA and PRN, albeit with low antibody level of PT and low titer in PTx CHO neutralization assay, as compared to control and GC DTaP vaccines. The raP vaccine provided a sterile lung bacterial clearance comparable to a commercial control vaccine after the experimental challenge in murine model. Moreover, raP exhibited a strong cytokine response and CD4+ TRM cell in lung tissue, comparable or superior to the experimental and commercial DTaP vaccinated groups. Contingent on improving the biophysical stability and humoral response to PT, the raP vaccine warrants further development as an effective alternative to aP vaccines for the control of a pertussis outbreak.

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.

Seroprevalence of varicella-zoster virus as measured by fluorescent antibody to membrane antigen assay and glycoprotein enzyme-linked immunosorbent assay more than 10 years after initiation of a universal vaccination program: An observational study.

Universal varicella vaccination (UVV), as a single dose to children aged 12 to 15 months, was introduced in Korea in 2005. A seroprevalence study is required to upgrade this UVV strategy. The fluorescent antibody to membrane antigen (FAMA) assay is the gold standard for varicella-zoster virus (VZV) immunity testing. However, no standard operating procedure (SOP) has been developed for the FAMA assay, in which either glutaraldehyde or acetone may be used for VZV-infected cell fixation. In this observational study, we aimed to investigate the age-specific seroprevalence in Korean children and adults. Additionally, with glycoprotein enzyme-linked immunosorbent assay (gpELISA) as the reference, we evaluated the performance of the FAMA assay using acetone-fixed cells. Four hundred sera were analyzed using the FAMA assay (acetone-fixed cells) and gpELISA, comprising 50 subjects from each age category. In the FAMA assay, the seropositivity rate decreased from 82.0% in the 1 to 4-year-old group to 58.0% in the 5 to 9-year-old group (95% confidence interval [CI]: 69.2-90.2 and 44.2-70.6, respectively; P = .009), while that in the gpELISA decreased from 80.0% to 52.0% (95% CI: 67.0-88.8 and 38.5-65.2, respectively; P = .003). In both methods, the seropositivity rates ranged from 95% to 100% in the population aged ≥ 20 years. We observed a significant correlation between the 2 methods, with a correlation coefficient of 0.795 (P < .001). In receiver operating characteristic analysis using the gpELISA results as a reference, the area under the curve for the FAMA assay was very high at 0.995 (95% CI: 0.990-1.000; P < .001). Compared to the gpELISA, the sensitivity, specificity, and kappa value of the FAMA assay were 99.4%, 79.3%, and 0.84 (nearly perfect), respectively. The seropositivity rate of the 5 to 9-year-old group indicated waning immunity over time and supported implementation of a second dose in the UVV program. The results of the FAMA assay were comparable to those of the gpELISA. Although further study is needed to standardize procedures, our results suggest that the FAMA assay using acetone-fixed cells can be used widely and can be included in a universal FAMA assay SOP.

Macrophage activation syndrome in neonatal lupus presenting with fever and rash.

Neonatal lupus can occur in infants born to mother with autoimmune disorders through transplacental auto-antibodies. Clinical manifestations in neonatal lupus include cutaneous lesions and hematologic or hepatobiliary findings resembling those seen in systemic lupus erythematosus. In autoimmune state, macrophage activation syndrome (MAS) represent a critical and potentially fatal complication that can result in mortality if not immediately identified and managed with the appropriate care. Here we present a 33-day-old girl diagnosed with neonatal lupus and serious MAS. She was delivered by a primipara mother who did not exhibit any autoimmune symptoms. The patient visited the hospital due to fever and pancytopenia. Laboratory data were compatible with MAS, including pancytopenia, high level of ferritin, soluble interleukin-2, and decreased natural killer cell activity. In addition, autoimmune study showed positive results for anti-nuclear antibody (ANA), anti-Sjogren syndrome antigen A (SSA), and SSB, The autoimmune study for mother also showed positive results for ANA, anti-SSA, and SSB. The patient recovered after she received high dose steroid and supportive care. Our case indicates that neonatal lupus should be taken into consideration when fever, erythematous skin rash, and pancytopenia are observed in infants, even if their mothers have no prior history of autoimmune conditions.

Volumetric changes in brain MRI of infants with hypoxic-ischemic encephalopathy and abnormal neurodevelopment who underwent therapeutic hypothermia.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication that can result in 40-60 % of long-term morbidity. Magnetic Resonance Imaging (MRI) is a noninvasive method which is usually performed before discharge to visually assess acquired cerebral lesions associated with HIE and severity of lesions possibly providing a guide for detecting adverse outcomes. This study aims to evaluate the impact of HIE on brain volume changes observed in MRI scans performed at a mean 10 days of life, which can serve as a prognostic indicator for abnormal neurodevelopmental (ND) outcomes at 18-24 months among HIE infants. METHODS: We retrospectively identified a cohort of HIE patients between June 2013 and March 2017. The inclusion criteria for therapeutic hypothermia (TH) were a gestational age ≥35 weeks, a birth weight ≥1800 g, and the presence of ≥ moderate HIE. Brain MRI was performed at a mean 10 days of life and brain volumes (total brain volume, cerebral volume, cerebellar volume, brain stem volume, and ventricle volume) were measured for quantitative assessment. At 18-24 months, the infants returned for follow-up evaluations, during which their cognitive, language, and motor skills were assessed using the Bayley Scales of Infant and Toddler Development III. RESULTS: The study recruited a total of 240 infants between 2013 and 2017 for volumetric brain MRI evaluation. Among these, 83 were normal control infants, 107 were TH-treated HIE infants and 37 were HIE infants who did not receive TH due to contraindications. Clinical evaluation was further proceeded. We compared the brain volumes between the normal control infants (n = 83) with normal ND but TH-treated HIE infants (n = 76), abnormal ND TH-treated HIE infants (n = 31), and the severe HIE MRI group with no TH (n = 37). The abnormal ND TH-treated HIE infants demonstrated a significant decrease in brainstem volume and an increase in ventricle size (p < 0.001) (Table 4). Lastly, the severe brain MRI group who did not receive TH showed significantly smaller brain stem (p = 0.006), cerebellar (p = 0.006) and cerebrum volumes (p = 0.027), accompanied by larger ventricular size (p = 0.013) compared to the normal control group (Table 5). CONCLUSION: In addition to assessing the location of brain injuries in MRI scans, the reduction in brain stem volume coupled with an increase in ventricular volume in HIE infants may serve as a biomarker indicating severe HIE and adverse long-term ND outcomes among HIE infants who either received therapeutic hypothermia (TH) treatment or not.

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.

Safety of Interchanging the Live Attenuated MAV/06 Strain and OKA Strain Varicella Vaccines in Children.

Two live attenuated varicella vaccine (VZV) strains have been mainly used across the globe: MAV/06 and OKA strains. We aimed to explore the safety of interchanging the two VZV strains for primary and booster immunizations. South Korea's vaccine adverse event reporting system (VAERS) was accessed and searched to find filed reports of all adverse events (AEs) following immunization with the second dose of the varicella vaccine. The electronic medical records were reviewed for all visits to the hospital following the second dose of the varicella vaccine. Of the total 406 study participants, 27.5% (n = 112) were in the MAV/06-MAV/06 group, 30.3% (n = 123) in the MAV/06-OKA, 17.5% (n = 71) in the OKA-MAV/06 group, and 24.6% (n = 100) in the OKA-OKA group. Mean age at immunization with the first dose was 1.10 (standard deviation [SD] ±0.34) years old, and second dose was 4.77 (SD ± 1.13) (p = 0.772 and 0.933, respectively). There were no filed reports of AEs following the second dose in the national VAERS. Hospital visit records showed a total of 10.3% (95% confidence interval [CI], 7.6-13.7) (n = 42) had recorded AEs following the 2nd administered dose; however, only 0.7% (95% CI, 0.2-2.4) (n = 3) were regarded as possibly vaccine related. Two patients in the MAV/06-OKA group were diagnosed with Henoch-Schonlein purpura after the second dose; however, both had also received the MMR vaccine on the same day. No safety signals associated with interchanging the MAV/06 and OKA strain live attenuated varicella vaccines were observed in this patient cohort of healthy children.

Kidney Organoid Derived from Human Pluripotent and Adult Stem Cells for Disease Modeling.

Kidney disease affects a significant portion of the global population, yet effective therapies are lacking despite advancements in identifying genetic causes. This limitation can be attributed to the absence of adequate in vitro models that accurately mimic human kidney disease, hindering targeted therapeutic development. However, the emergence of human induced pluripotent stem cells (PSCs) and the development of organoids using them have opened up a way to model kidney development and disease in humans, as well as validate the effects of new drugs. To fully leverage their capabilities in these fields, it is crucial for kidney organoids to closely resemble the structure and functionality of adult human kidneys. In this review, we aim to discuss the potential of using human PSCs or adult kidney stem cell-derived kidney organoids to model genetic kidney disease and renal cancer.