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Abstract Several perinatal factors influence the intestinal microbiome of newborns during the first days of life, whether during delivery or even in utero. These factors may increase the risk of developing necrotizing enterocolitis (NEC) by causing dysbiosis linked to a NEC-associated microbiota, which may also be associated with other gastrointestinal problems. The objective of our study was to evaluate the potential risks associated with microbial shifts in newborns with gastrointestinal symptoms and identify the intestinal microbiota of neonates at risk for NEC.During the study period, 310 preterm and term newborns’ first passed meconium occurring within 72 h of birth were collected, and the microbiome was analyzed. We identified the risk factors in the NEC/FI group. Regarding microbiota, we compared the bacterial abundance between the NEC/FI group at the phylum and genus levels and explored the differences in the microbial composition of the 1st stool samples. A total of 14.8% (n = 46) of the infants were diagnosed with NEC or FI. In univariate analysis, the mean gestational age and birth weight were significantly lower in the NEC/FI group (p 18 h, chorioamnionitis, and histology were significantly higher in the NEC/FI group (p 18 h), and early onset sepsis were consistently associated with an increased risk of NEC/FI. Infants diagnosed with NEC/FI exhibited a significantly lower abundance of Actinobacteria at the phylum level than the control group (p

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

BackgroundAcinetobacter 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. MethodsACB 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.ResultsDuring 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

Abstract 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

Abstract 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

Objective: This study aimed to compare the efficacy and tolerability of azithromycin and clarithromycin in pediatric Campylobacter enterocolitis. Methods: A prospective, randomized, controlled trial was conducted at a single center. Patients with confirmed Campylobacter enterocolitis were randomly assigned to receive either a 3-day course of azithromycin or a 5-day course of clarithromycin. Symptoms were monitored daily, and changes in laboratory markers (WBC counts, CRP levels, and stool calprotectin) were compared. Results: A total of 29 pediatric patients were included, with 14 patients in the azithromycin group and 15 patients in the clarithromycin group. The median age of patients in the azithromycin group was 10.0 years (interquartile range [IQR]: 5.0–13.0), and in the clarithromycin group, the median age was 9.0 years (IQR: 7.0–13.0) (p = 0.793). The median time to clinical resolution was 3.0 days (IQR: 2.0–3.0) in the azithromycin group and 2.0 days (IQR: 2.0–3.0) in the clarithromycin group (p = 0.132). There were no significant differences in the duration of individual symptoms, including fever, vomiting, and abdominal pain. The length of hospital stay was also similar, with a median stay of 4 days (IQR: 3.0–5.0) in both groups (p = 0.394). Both antibiotics were well-tolerated, with no significant adverse events or treatment discontinuation reported. Conclusions: Clarithromycin was found to be as effective as azithromycin in treating pediatric Campylobacter enterocolitis, with similar clinical outcomes and improvements in laboratory markers.

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.

Abstract Introduction This study aimed to assess the role of adenosine triphosphate (ATP) bioluminescence level monitoring for identifying reservoirs of the outbreak pathogen during two consecutive outbreaks caused by Enterococcus faecium and Staphylococcus capitis at a neonatal intensive care unit (NICU). The secondary aim was to evaluate the long-term sustainability of the infection control measures employed one year after the final intervention measures. Methods Two outbreaks occurred during a 53-day period in two disconnected subunits, A and B, that share the same attending physicians. ATP bioluminescence level monitoring, environmental cultures, and hand cultures from healthcare workers (HCW) in the NICU were performed. Pulsed-field gel electrophoresis (PFGE) typing was carried out to investigate the phylogenetic relatedness of the isolated strains. Results Four cases of E. faecium sepsis (patients A-8, A-7, A-9, B-8) and three cases of S. capitis sepsis (patients A-16, A-2, B-8) were diagnosed in six preterm infants over a span of 53 days. ATP levels remained high on keyboard 1 of the main station (2076 relative light unit [RLU]/100 cm2) and the keyboard of bed A-9 (4886 RLU/100 cm2). By guidance with the ATP results, environmental cultures showed that E. faecium isolated from the patients and from the main station’s keyboard 1 were genotypically indistinguishable. Two different S. capitis strains caused sepsis in three patients. A total 77.8% (n = 7/9) of S. capitis cultured from HCW's hands were genotypically indistinguishable to the strains isolated from A-2 and A-16. The remaining 22.2% (n = 2/9) were genotypically indistinguishable to patient B-8. Three interventions to decrease the risk of bacterial transmission were applied, with the final intervention including a switch of all keyboards and mice in NICU-A and B to disinfectable ones. Post-intervention prospective monitoring up to one year showed a decrease in blood culture positivity (P = 0.0019) and catheter-related blood stream infection rate (P = 0.016) before and after intervention. Conclusion ATP monitoring is an effective tool in identifying difficult to disinfect areas in NICUs. Non-medical devices may serve as reservoirs of pathogens causing nosocomial outbreaks, and HCWs' hands contribute to bacterial transmission in NICUs.

Abstract 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

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

Abstract Background Spastin significantly influences microtubule regulation in neurons and is implicated in the pathogenesis of hereditary spastic paraplegia (HSP). However, post-translational regulation of the spastin protein remains nebulous. The association between E3 ubiquitin ligase and spastin provides a potential therapeutic strategy. Results As evidenced by protein chip analysis, FBXL17 inversely correlated with SPAST-M1 at the protein level in vitro and, also in vivo during embryonic developmental stage. SPAST-M1 protein interacted with FBXL17 specifically via the BTB domain at the N-terminus of SPAST-M1. The SCFFBXL17 E3 ubiquitin ligase complex degraded SPAST-M1 protein in the nuclear fraction in a proteasome-dependent manner. SPAST phosphorylation occurred only in the cytoplasmic fraction by CK2 and was involved in poly-ubiquitination. Inhibition of SCFFBXL17 E3 ubiquitin ligase by small chemical and FBXL17 shRNA decreased proteasome-dependent degradation of SPAST-M1 and induced axonal extension. The SPAST Y52C mutant, harboring abnormality in BTB domain could not interact with FBXL17, thereby escaping protein regulation by the SCFFBXL17 E3 ubiquitin ligase complex, resulting in loss of functionality with aberrant quantity. Although this mutant showed shortening of axonal outgrowth, low rate proliferation, and poor differentiation capacity in a 3D model, this phenotype was rescued by inhibiting SCFFBXL17 E3 ubiquitin ligase. Conclusions We discovered that a novel pathway, FBXL17-SPAST was involved in pathogenicity of HSP by the loss of function and the quantitative regulation. This result suggested that targeting FBXL17 could provide new insight into HSP therapeutics.

Abstract Background In women with autoimmune rheumatic disorders (ARD), pregnancy complications or postpartum events are more frequent compared to the general population. Transplacental autoantibodies or cytokines influence various fetal and neonatal outcomes. We compared the growth patterns of babies born to mothers with ARD versus healthy mothers to assess the long-term growth outcomes of children born to women with ARD. Methods This was a retrospective age-matched cohort analyses of babies born to mothers with ARD from the hospitals belonging to the Catholic University of Korea between 2010 and 2017. Demographic and autoimmune laboratory test data of the mothers and newborns were assessed. Neonatal growth was measured in terms of height and weight, measured at birth and follow-up examinations. Results We enrolled 142 infants from mothers with ARD and 149 infants from healthy mothers. There was no significant difference between mothers with ARD and healthy mothers in terms of delivery age, parity, abortion, and premature delivery history. The mothers with ARD were diagnosed with systemic lupus erythematosus (81%), Sjogren syndrome (6%), and other autoimmune phenomena (11%). The groups were significantly different in terms of neonatal characteristics such as prematurity, gestational age, birth weight, and height, but not in Apgar score and delivery type. For most neonates, autoimmune laboratory results were normalized within 1 year, except for anti-La/SSB antibody, which remained high in some. The height and weight for age z-score were lower than the normal age groups at birth but showed catch-up growth by 2 years of age. Conclusions Low birthweight and prematurity at birth for neonates born to mothers with ARD could be caught up by 2 years of age, and maternal ARD does not affect the growth of their offspring.

The human microbiome, which consists of a collective cluster of commensal, symbiotic, and pathogenic microorganisms living in the human body, plays a key role in host health and immunity. The human nasal cavity harbors commensal bacteria that suppress the colonization of opportunistic pathogens. However, dysbiosis of the nasal microbial community is associated with many diseases, such as acute respiratory infections including otitis media, sinusitis and bronchitis and allergic respiratory diseases including asthma. The nasopharyngeal acquisition of pneumococcus, which exists as a pathobiont in the nasal cavity, is the initial step in virtually all pneumococcal diseases. Although the factors influencing nasal colonization and elimination are not fully understood, the adhesion of opportunistic pathogens to nasopharyngeal mucosa receptors and the eliciting of immune responses in the host are implicated in addition to bacterial microbiota properties and colonization resistance dynamics. Probiotics or synbiotic interventions may show promising and effective roles in the adjunctive treatment of dysbiosis; however, more studies are needed to characterize how these interventions can be applied in clinical practice in the future.

ABSTRACT: Background: Nasopharyngeal (NP) colonization with Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) is common in children, and may evolve as the source of invasive infections. In Korea, the pneumococcal conjugate vaccines (PCVs) were introduced >10 years ago, enabling the authors to study the effect of the vaccine in preventing carriage. Methods: NP swabs were taken and a household survey was conducted at daycare centres located in different regions of Korea in 2014 and 2019. Pneumococcal serotypes were identified using the Quellung method and sequencing. NTHi were identified based on pilA and bexA genes. Results: In total, 1460 NP swabs were obtained with pneumococcal carriage rates of 36.4–42.1% and NTHi carriage rates of 36.5–26.7%. Among children carrying pneumococci, a significant increase was seen in serotype 23A between 2014 and 2019 (from 12.6% to 22.0%; P=0.005). Children who had received PCV were at lower risk of vaccine-type carriage (2.9% vs 0.8%; P=0.005). Conclusions: Between 2014 and 2019, the proportion of children carrying serotype 23A increased significantly, while the carriage rate of NTHi decreased. Continuous surveillance is needed to assess the long-term effects of the PCVs on carriage dynamics of pneumococcus and NTHi.

Background To date, nephrotoxicity in new drug development has been evaluated through two-dimensional culture of representative cell lines, such as HK-2 and human proximal tubule epithelial cells (hPTECs). Approximately 20% of new drugs that were safe in preclinical studies were withdrawn from clinical trials due to nephrotoxicity, which means the current renal cell lines used in preclinical trials have limitations for the accurate detection of nephrotoxicity. Methods and Results Here, we established proximal tubule cell lines from immortalized mixed primary renal cells and generated functional proximal tubule cell spheroids, which expressed all apical basolateral transporters and showed epithelial polarity. Moreover, they showed a more sensitive drug response than hPTECs, which have been commonly used as in vitro kidney models. Conclusion Taken together, the proximal tubule cells described in this study provide a more stable, reproducible, and accurate in vitro kidney model for predicting nephrotoxicity, which could help early compound development.

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.

Humanity has been suffering from the global severe acute respiratory syndrome coronavirus 2 pandemic that began late in 2019. In 2020, for the first time in history, new vaccine platforms—including mRNA vaccines and viral vector-based DNA vaccines—have been given emergency use authorization, leading to mass vaccinations. The purpose of this article is to review the currently most widely used coronavirus disease 2019 vaccines, investigate their immunogenicity and efficacy data, and analyze the vaccine safety profiles that have been published, to date.

Background Understanding the epidemiology and prevalence of febrile urinary tract infection (fUTI) in children is important for risk stratification and selecting appropriate urine sample collection candidates to aid in its diagnosis and treatment. Purpose This study aimed to analyze the epidemiology, etiology, and changes in antibiotic susceptibility patterns of the first fUTI in children. Methods This retrospective observational cohort study included children younger than 19 years of age who were diagnosed and treated for their first fUTI in 2006–2016. Electronic medical records were analyzed and radiologic images were evaluated. Results A total of 359 patients (median age, 5.1 months; interquartile range, 3.0–10.5 months) fit the inclusion criteria; of them, 78.0% (n=280) were younger than 12 months old. The male to female ratio was 5.3:1 for patients aged 0–2 months, 2.1:1 for those 3–5 months, and 1.6:1 for those 6–11 months. Beyond 12 months of age, there was a female predominance. Escherichia coli was the leading cause (83.8%), followed by Enterococcus species (6.7%), and Klebsiella pneumoniae (3.6%). Significant yearly increases in the proportions of multidrug-resistant strains (P

Background: The cellular senescence of primary cultured cells is an irreversible process characterized by growth arrest. Restoration of senescence by ginsenosides has not been explored so far. Rg3(S) treatment markedly decreased senescence-associated β-galactosidase activity and intracellular reactive oxygen species levels in senescent human dermal fibroblasts (HDFs). However, the underlying mechanism of this effect of Rg3(S) on the senescent HDFs remains unknown. Methods: We performed a label-free quantitative proteomics to identify the altered proteins in Rg3(S)-treated senescent HDFs. Upregulated proteins induced by Rg3(S) were validated by real-time polymerase chain reaction and immunoblot analyses. Results: Finally, 157 human proteins were identified, and variable peroxiredoxin (PRDX) isotypes were highly implicated by network analyses. Among them, the mitochondrial PRDX3 was transcriptionally and translationally increased in response to Rg3(S) treatment in senescent HDFs in a time-dependent manner. Conclusion: Our proteomic approach provides insights into the partial reversing effect of Rg3 on senescent HDFs through induction of antioxidant enzymes, particularly PRDX3. Keywords: Ginsenoside Rg3(S), Human dermal fibroblast, Label-free quantitative proteomics, Restoration, Senescence

Serious bacterial infection (SBI) in children, such as bacterial meningitis or sepsis, is an important condition that can lead to fatal outcomes. Therefore, since it is very important to accurately diagnose SBI, SBI prediction tools such as 'Refined Lab-score' or 'clinical prediction rule' have been developed and used. However, these tools can predict SBI only when there are values of all factors used in the tool, and if even one of them is missing, the tools become useless. Therefore, the purpose of this study was to develop and validate a machine learning-driven model to predict SBIs among febrile children, even with missing values. This was a multicenter retrospective observational study including febrile children

The primary aim of this study was to investigate the compositional differences of the first passed meconium microbiome in preterm and term infants, and the secondary aim was to compare the meconium microbiomes of preterm and term infants that later developed necrotizing enterocolitis (NEC)/Feeding intolerance (FI) compared to those that did not develop NEC/FI. During the study period, a total of 108 preterm and term newborns' first passed meconium occurring within 72 hours of birth were collected and microbiome analyzed. Meconium microbiomes showed a disruption in the percentages of the core microbiome constituents in both the phylum and genus levels in infants born < 30 weeks of gestational age (GA) compared to those born ≥ 30 weeks of GA. In the phylum level, Bacteroidetes and Firmicutes, and in the genus level, Prevotella and Bacteroides, were predominant, with Prevotella accounting for 20–30% of the relative abundance. As GA increased, a significant increase in the relative abundance of Bacteroidetes (P for trend < 0.001) and decrease in Proteobacteria (P for trend = 0.049) was observed in the phylum level. In the genus level, as GA increased, Prevotella (P for trend < 0.001) and Bacteroides (P for trend = 0.002) increased significantly, whereas Enterococcus (P for trend = 0.020) decreased. Compared to the control group, the meconium of infants that later developed NEC/FI had significantly lower alpha diversities but similar beta-diversities. Furthermore, the NEC/FI group showed a significantly lower abundance of Bacteroidetes (P < 0.001), and higher abundance of Firmicutes (P = 0.034). To conclude, differences were observed in the composition of the first passed meconium in preterm and term infants that later develop NEC/FI compared to those that did not.

IMPORTANCE:. Factors associated with mortality in coronavirus disease 2019 patients on invasive mechanical ventilation are still not fully elucidated. OBJECTIVES:. To identify patient-level parameters, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation or coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS:. Prospective observational cohort study by the global Coronavirus Disease 2019 Critical Care Consortium. Patients with laboratory-confirmed coronavirus disease 2019 requiring invasive mechanical ventilation from February 2, 2020, to May 15, 2021. MAIN OUTCOMES AND MEASURES:. Patient characteristics and clinical data were assessed upon ICU admission, the commencement of invasive mechanical ventilation and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day invasive mechanical ventilation mortality. RESULTS:. One-thousand five-hundred eighty-seven patients were included in the survival analysis; 588 patients died in hospital within 28 days of commencing invasive mechanical ventilation (37%). Cox-regression analysis identified associations between the hazard of 28-day invasive mechanical ventilation mortality with age (hazard ratio, 1.26 per 10-yr increase in age; 95% CI, 1.16–1.37; p < 0.001), positive end-expiratory pressure upon commencement of invasive mechanical ventilation (hazard ratio, 0.81 per 5 cm H2O increase; 95% CI, 0.67–0.97; p = 0.02). Time-dependent parameters associated with 28-day invasive mechanical ventilation mortality were serum creatinine (hazard ratio, 1.28 per doubling; 95% CI, 1.15–1.41; p < 0.001), lactate (hazard ratio, 1.22 per doubling; 95% CI, 1.11–1.34; p < 0.001), Paco2 (hazard ratio, 1.63 per doubling; 95% CI, 1.19–2.25; p < 0.001), pH (hazard ratio, 0.89 per 0.1 increase; 95% CI, 0.8–14; p = 0.041), Pao2/Fio2 (hazard ratio, 0.58 per doubling; 95% CI, 0.52–0.66; p < 0.001), and mean arterial pressure (hazard ratio, 0.92 per 10 mm Hg increase; 95% CI, 0.88–0.97; p = 0.003). CONCLUSIONS AND RELEVANCE:. This international study suggests that in patients with coronavirus disease 2019 on invasive mechanical ventilation, older age and clinically relevant variables monitored at baseline or sequentially during the course of invasive mechanical ventilation are associated with 28-day invasive mechanical ventilation mortality hazard. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.

In the last few decades, macrolide-resistant Mycoplasma pneumoniae (MRMP) has been increasing in proportion. This study aimed to evaluate the treatment outcomes of children with lobar or segmental MP pneumonia unresponsive to the initial 3–5-day macrolide therapy, who then switched to either a non-macrolide, macrolide + steroid, or a non-macrolide + steroid regimen, according to the 2019 KSPID and KAPARD guideline during the 2019–2020 Mycoplasma epidemic in South Korea. A total of 190 patients n = 32/190) were responsive to the initial macrolide monotherapy, whereas 83.2% (158/190) were refractory. The median age of the patients was 7 (interquartile range [IQR], 5–9) years old and 46.2% (n = 73/158) were male. The overall treatment success rates of non-macrolide, macrolide + steroid, and non-macrolide + steroid groups were 46.2%, 80.8%, and 100.0%, respectively. Patients in the non-macrolide + steroid group had the shortest fever duration after a regimen change of 1 (IQR, 0–3) day compared with patients in the non-macrolide group and macrolide + steroid group; 2 (IQR, 1–4) days and 2 (IQR, 1–3.3) days (p = 0.004), respectively. Follow-up CRP (ß, 0.169; CI, 0.050–0.287; p = 0.006), macrolide + steroid therapy (ß, −1.694; CI, −2.463–−0.925; p < 0.001), and non-macrolide+ steroid therapy (ß, −2.224; CI, −3.321–−1.127; p < 0.001) were shown to be significantly associated with the duration of fever after admission. To conclude, in patients with severe MP pneumonia that failed to respond to the initial macrolide therapy, a non-macrolide + steroid had the highest treatment success rate and a shorter duration of fever.

Infectious diarrhea is a global pediatric health concern; therefore, rapid and accurate detection of enteropathogens is vital. We evaluated the BioFire® FilmArray® Gastrointestinal (GI) Panel with that of comparator laboratory tests. Stool samples of pediatric patients with diarrhea were prospectively collected and tested. As a comparator method for bacteria, culture, conventional PCR for diarrheagenic E. coli, and Allplex GI-Bacteria(I) Assay were tested. For discrepancy analysis, BD MAX Enteric Bacterial Panel was used. As a comparator method for virus, BD MAX Enteric Virus Panel and immunochromatography was used and Allplex GI-Virus Assay was used for discrepancy analysis. The “true positive” was defined as culture-positive and/or positive results from more than two molecular tests. Of the 184 stool samples tested, 93 (50.5%) were true positive for 128 pathogens, and 31 (16.9%) were positive for multiple pathogens. The BioFire GI Panel detected 123 pathogens in 90 of samples. The BioFire GI Panel demonstrated a sensitivity of 100% for 12 targets and a specificity of >95% for 16 targets. The overall positive rate and multiple pathogen rate among patients in the group without underlying diseases were significantly higher than those in the group with hematologic disease (57.0% vs. 28.6% (p = 0.001) and 20.4% vs. 4.8% (p = 0.02), respectively). The BioFire GI Panel provides comprehensive results within 2 h and may be useful for the rapid identification of enteropathogens.

After primary infection, varicella zoster virus (VZV) causes prolonged latent infections that may reactivate, depending on the immunologic status of the host. We present a case of VZV reactivation in a 10-year-old male patient that underwent unrelated peripheral blood stem cell transplantation (uPBSCT) for T-lymphoblastic lymphoma with lymphoma cutis lesions. This patient had a history of herpes zoster involving the right L2-5 dermatome and trigeminal V1 dermatome prior to uPBSCT. Three months post-uPBSCT, the patient’s underlying disease relapsed, and the patient presented with lymphoma cutis lesions. A few days after a skin biopsy was performed to pathologically confirm skin relapse, vesicles appeared only involving the skin areas with lymphoma cutis. This case illustrates how decreased areas of epidermal immune mechanisms may cause atypical presentations of varicella infection.

Septicemia or bacteremia is one of the leading causes of death worldwide. Long-term tunneled central venous catheters (CVCs) are usually placed in children undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT) for underlying hemato–oncologic malignancies. However, catheter-related complications have been reported frequently, and there is high morbidity and mortality related to catheter-line-associated bloodstream infections (CLABSIs). We report a rare case of six episodes of recurrent K. pneumoniae sepsis within a 6-month period in a 12-year-old male adolescent that underwent HSCT for acute lymphoblastic leukemia, despite treatment with susceptible antibiotics. The patient received extensive diagnostic evaluations to find the hidden source; however, failure to discover the primary source led to multiple recurrences. Through enterobacterial repetitive intergenic consensus (ERIC)-PCR, we were able to identify the relationship between the six episodes and recognize the source of bacteremia.

Conventional methods for etiologic diagnoses of acute gastroenteritis (AGE) are time consuming and have low positive yield leading to limited clinical value. This study aimed to investigate quality improvements in patient management, antibiotic stewardship, and in-hospital infection transmission prevention using BioFire® FilmArray® Gastrointestinal Panel (GI Panel) in children with acute diarrhea. This was a prospective study recruiting children < 19 years old with new onset diarrhea during the study period, and a matched historical cohort study of children diagnosed with AGE during the 4 years prior. Patients in the prospective cohort underwent stool testing with GI Panel and conventional methods. A total of 182 patients were included in the prospective cohort, of which 85.7% (n = 156) had community-onset and 14.3% (n = 26) had hospital-onset diarrhea. A higher pathogen positivity rate for community-onset diarrhea was observed by the GI Panel (58.3%, n = 91) compared to conventional studies (42.3%, n = 66) (p = 0.005) and historical cohort (31.4%, n = 49) (p < 0.001). The stool tests reporting time after admission was 25 (interquartile range, IQR 17–46) hours for the GI Panel, and 72 (IQR 48–96) hours for the historical cohort (p < 0.001). A significant reduction in antibiotic use was observed in the prospective cohort compared to historical cohort, 35.3% vs. 71.8%; p < 0.001), respectively. Compared to the GI Panel, norovirus ICT was only able to detect 4/11 (36.4%) patients with hospital-onset and 14/27 (51.8%) patients with community-onset diarrhea. The high positivity rate and rapid reporting time of the GI Panel had clinical benefits for children admitted for acute diarrhea, especially by reducing antibiotic use and enabling early adequate infection precaution and isolation.

Background: Kawasaki disease (KD) may be associated with infection of unknown pathogen(s). For predicting of the etiology of KD, we evaluated epidemiological characteristics in KD, common infectious diseases and immune-mediated diseases in childhood.Methods: We respectively, reviewed the data of patients with KD, influenza, aseptic meningitis, exanthem subitum (ES), Mycoplasma pneumoniae (MP) pneumonia, acute pyelonephritis (APN), Henoch-Schönlein purpura (HSP), acute poststreptococcal glomerulonephritis (APSGN), and childhood asthma. We compared and interpreted epidemiological data across the groups.Results: In age distribution, KD, APN, and ES showed a similar pattern in that majority of patients were infants or young children, and other diseases showed a relatively even age-distribution which had a peak age, mainly 5–6 years, with bell-shape patterns. In annual-case pattern, there were epidemic years in aseptic meningitis and MP pneumonia, and the fluctuated annual cases were seen in other diseases. The trends of decreasing cases were seen in APSGN, HSP, and childhood asthma in recent years. In seasonal frequency, influenza or aseptic meningitis occurred in mainly winter or summer season, respectively. HSP and APSGN cases had less in summer, and KD, APN, and ES showed relatively even occurrence throughout a year without significant seasonal variations.Conclusions: Our results suggest that KD agents may be associated with normal flora that are influenced by environmental changes, since pathogens of APN and ES could be regarded as normal flora that originate from the host itself or ubiquitously existing human reservoirs.

The aim of the present study is to re-evaluate the clinical application of two-times serologic immunoglobulin M (IgM) tests using microparticle agglutination assay (MAA), an enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) assay in diagnosing Mycoplasma pneumoniae (MP) infection. A retrospective analysis of 62 children with MP pneumonia during a recent epidemic (2019–2020) was conducted. The MAA and ELISA immunoglobulin M (IgM) and IgG measurements were conducted twice at admission and around discharge, and MP PCR once at presentation. Diagnostic rates in each test were calculated at presentation and at discharge. The seroconverters were 39% (24/62) of patients tested by MAA and 29% (18/62) by ELISA. At presentation, the diagnostic positive rates of MAA, ELISA, and PCR tests were 61%, 71%, and 52%, respectively. After the second examination, the rates were 100% in both serologic tests. There were positive correlations between the titers of MAA and the IgM values of ELISA. The single serologic IgM or PCR tests had limitations to select patients infected with MP in the early stage. The short-term, paired IgM serologic tests during hospitalization can reduce patient-selection bias in MP infection studies.

Monitoring regional antibiotic resistance patterns of uropathogens are important for deciding suitable empirical antibiotics for urinary tract infections (UTIs) in children. This study aimed to investigate regional differences in antimicrobial susceptibility patterns of E. coli and Klebsiella spp. in children below 24 months old, diagnosed with their first episode of UTI, and to find factors associated with an increased risk for UTI caused by extended-spectrum β-lactamase (ESBL)-producing uropathogens. This was a retrospective cohort study of children diagnosed between 2011 and 2017 in four different hospitals located in four different regions of South Korea; regions A, B, C, and D. The government’s big data repository was used to acquire data on regional antibiotic prescriptions. The pooled antimicrobial susceptibilities of E. coli and Klebsiella spp. (n = 2044) were as follows: ampicillin–sulbactam (61.0%), 3rd generation cephalosporin (3C) (82.8%), and trimethoprim–sulfamethoxazole (72.0%). Multivariate analysis showed that children diagnosed at hospital A (OR, 1.8; 95% confidence interval [CI], 1.2–2.6; P = 0.002) and every year that increased in the study period (OR, 1.1; 95% CI, 1.1–1.2; P < 0.001) were factors associated with an increased risk for UTIs with ESBL-producers. Regions A and B had significantly higher amounts of oral 3Cs prescribed compared to regions C and D (P = 0.009), which correlate with hospitals in the regions that had higher proportions of UTIs with ESBL-producing uropathogens (A and B vs. C and D, P < 0.001). Therefore, children in certain regions are at a higher risk for UTIs caused by ESBL-producers compared to other regions, which correlate with regions that had higher amounts of oral 3Cs prescribed.

The kidney has a tremendous capacity to regenerate following injury, but factors that govern this response are still largely unknown. We isolated cells from mouse kidneys with high proliferative and multi-lineage differentiation capacity. These cells expressed a high level of Sox9. In regenerating kidneys, Sox9 expression was induced early, and 89% of proliferating cells were Sox9 positive. In vitro, Sox9-positive cells showed unlimited proliferation and multi-lineage differentiation capacity. Using an inducible Sox9 Cre line and lineage-tagging methods, we show that Sox9-positive cells can generate new daughter cells, contributing to the regeneration of proximal tubule, loop of Henle, and distal tubule segments but not to collecting duct and glomerular cells. Furthermore, inducible deletion of Sox9 resulted in reduced epithelial proliferation, more severe injury, and fibrosis development. In summary, we demonstrate that, in the kidney, Sox9-positive cells show progenitor-like properties in vitro and contribute to epithelial regeneration following injury in vivo.

The family Eolepadidae is the only stalked barnacle in hydrothermal vent regions. Here, we determined the mitogenome of the eolepadid Vulcanolepas fijiensis. The mitogenome was 17,374 bp long, with 76.6% AT content. Its protein-coding gene organization was identical to that of the deep-sea scalpellid Arcoscalpellum epeeum. On the mitogenomic tree, two scalpellomorphan families (Eolepadidae and Scalpellidae) were monophyletic while the other scalpellomorphan family Pollicipedidae did not form the monophyletic group with them. Further mitogenomic analysis of undetermined taxa in hydrothermal vents is required to deepen our understanding of their phylogenetic relationships.

Scalpellids are one of the largest families of Scalpelliformes and reproduce either androdioeciously or dioeciously. Here, we characterized the first mitogenome of a scalpellid barnacle (Arcoscalpellum epeeum), which was 15,593 bp in length with a 71.5% AT content. In comparison with the pollicipedids Capitulum mitella and Pollicipes polymerus, the tRNA genes of A. epeeum were rearranged between ND3 and ND5, between CYTB and ND1, and between 12S rRNA and ND2. On the mitogenomic tree, the Scalpelliformes families Pollicipedidae and Scalpellidae were not monophyletic, which concurs with previous studies.

The family Catophragmidae is one of the lower balanomorphs from traditional and recent multiple mitochondrial and nuclear markers molecular analysis. Here, we characterized the first mitogenome of the catophragmid barnacle Catomerus polymerus, which was 15,446 bp in length with a 68.3% AT content. The mitogenome had the typical pancrustacean gene arrangement, which was identical to the mitogenome configurations of the chthamalid Octomeris sp. and pachylasmatoid Eochionelasmus ohtai. On the mitogenomic tree, the catophragmid Catomerus polymerus formed an independent branch that was basal to the members of the superfamilies Tetraclitoidea and Balanoidea, which was inconsistent with previous findings.

In Korea, Mycoplasma pneumoniae was detected in 255/2,089 respiratory specimens collected during 2000–2011; 80 isolates carried 23S rRNA gene mutations, and 69/123 culture-positive samples with the mutation were resistant to 5 macrolides. During 2000–2011, prevalence of the mutation increased substantially. These findings have critical implications for the treatment of children with mycoplasma pneumonia.

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 NBACB 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 blaoxa23 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 blaoxa23 gene. [ABSTRACT FROM AUTHOR]

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-tetanusacellular 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. [ABSTRACT FROM AUTHOR]