The close relationship between bile acid (BA) metabolism and sepsis has been investigated in recent years, as knowledge of the role of the gut microbiome and metabolomics in sepsis has grown and become more comprehensive.
Patients with sepsis who were admitted to the PICU of the Children’s Hospital, Zhejiang University School of Medicine from January 2016 to December 2021 were enrolled in this study. Preoperative non-infectious pediatric patients undergoing elective surgeries in our hospital’s department of surgery were recruited as controls during the same period. Clinical data were collected and analyzed.
702 children were enrolled, comprising 538 sepsis survivors, 164 sepsis fatalities, and 269 non-infected controls. Statistical analysis revealed that total BA (TBA) increased in both the early and severe stages of pediatric sepsis. In the severe stage, TBA (OR = 2.898, 95% CI 1.946–4.315, p < 0.05) was identified as a risk factor for sepsis. A clinical model identified TBA (the cut-off value is >17.95 µmol/L) as an independent predictor of sepsis mortality with an AUC of 0.842 (95% CI 0.800–0.883), sensitivity of 54.9%, specificity of 96.6%, and HR = 7.658 (95% CI 5.575–10.520).
The study showed that elevated TBA was associated with a heightened risk of mortality in pediatric sepsis.
Many clinical indicators show differences between children with sepsis and the control group, among which the difference in serum total bile acid levels is the most significant.
During the hospitalization of the patients, the overall bile acid levels in the sepsis death group were higher and exhibited greater fluctuations compared to the survival group, with significant differences.
Serum total bile acid levels can serve as effective biomarker for predicting the prognosis of children with sepsis.
Pediatric Burkitt lymphoma (pBL) is the most common non-Hodgkin lymphoma in children. These patients require prompt diagnosis and initiation of therapy due to rapid tumor growth. The roles of tumor tissue and circulating microRNAs (miRNAs) in the diagnosis or prognostication have not been fully elucidated in pBLs.
Differentially expressed (DE) miRNAs were identified with microRNA sequencing (miRNA-Seq) in tumor tissues and plasma of diagnostic pBLs. The diagnostic potential of total miRNA concentrations and overexpressed miRNAs were evaluated through receiver operating characteristic (ROC) analyses. Log-rank test was employed to evaluate survival differences associated with DE miRNAs. Selected miRNA expressions were cross-validated with quantitative reverse transcription PCR (qRT-PCR).
Total circulating cell-free miRNAs were higher in pBL cases compared to controls. Cancer-associated pathways were enriched among miRNAs differentially expressed in pBL tumor tissues. Several upregulated miRNAs in pBL tumors demonstrated high diagnostic potential. Similarly, ROC analysis of overexpressed plasma miRNAs revealed circulating cell-free or exosomal miRNAs that can distinguish pBLs from control cases. Indeed, integrative analysis of overexpressed circulating exosomal miRNAs showed an enhanced diagnostic potential for certain triple combinations. Kaplan–Meier analyses of DE miRNAs in tumor tissues identified miRNAs predicting overall survival.
Differentially expressed miRNAs in tumor tissue and plasma of pBL have the potential to improve diagnosis and prognosis.
Differentially expressed miRNAs in treatment-naive pediatric Burkitt lymphoma cases have diagnostic or prognostic biomarker potential.
This is the first study that applied miRNA-Seq on treatment-naive pediatric Burkitt lymphoma cases for identification of differentially expressed miRNAs both in tumor tissue and plasma samples with diagnostic potential.
Through systematic analysis of differentially expressed miRNAs, tumor tissue miRNAs associated with the overall survival of pBLs have been discovered.
The clinically significant, differentially expressed miRNAs identified in pediatric Burkitt lymphoma cases can potentially improve the current tissue-based or non-invasive clinical practice in terms of diagnosis or prognostication.
We aimed to investigate the association between developmental screening before 24 months of age and neurodevelopmental disorders (NDDs) at 4–6 years of age.
We included 922,899 newborn born between 2014 and 2016 registered in National Health Insurance Service (NHIS). Developmental screening was administered at 9–12 and 18–24 months old with the Korean Developmental Screening Test for Infants & Children (K-DST). Diagnoses of NDDs was based on the World Health Organization’s International Classification of Diseases, Tenth Revision (ICD-10), provided by the NHIS database.
Among 637,277 individuals who underwent screening at 9–12 and 18–24 months, Screen-positivity (defined as summed score < −2 standard deviation) for gross motor domain at 9–12 months was significantly associated with the incidence of autism spectrum disorder (aHR, 2.24; 95% CI, 1.80–2.80) and cerebral palsy (aHR, 4.81; 95% CI, 3.62–6.38). Screening positive at language domain at 18–24 months old was associated with autism spectrum disorder (aHR 5.50; 95% CI, 4.31– 7.02) and developmental language disorder (aHR 8.67; 95% CI, 7.27–10.33) at 4–6 years of age.
Widespread nationwide implementation of screening programs before 24 months was effective in identifying NDDs at 4–6 years of age. Further strategies integrating with referral and intervention systems should be established.
We investigated the screening effect of nationwide developmental screening program on neurodevelopmental disorders using nationwide data.
Gross motor delay during infancy was significant predictor of later neurodevelopmental disorders.
Language, cognitive, and social delay before 24 months of age was associated with later autism spectrum disorders and developmental language disorders.
Widespread nationwide implementation of screening programs before 24 months was effective in identifying NDDs at 4–6 years of age and should be encouraged.
During my fellowship, I had the privilege of conducting research in the Medical Genetics lab under the mentorship of Dr. Hope Northrup and Dr. Kit Sing Au. My research focused on genetic variants in folate transporter genes associated with myelomeningocele,1,2 an experience that ignited my appreciation for the process of discovery involved in research. Although I initially felt uncertain about pursuing a research career due to a relatively late start in the lab, the support of amazing mentors, such as Dr. Louise McCullough, empowered me to establish myself in translational research in congenital heart defects. My current research explores sex differences in the effects of chronic hypoxia on the myocardium in neonates with congenital heart disease. Our recent work published in Pediatric Research reflects the work made possible due to the efforts of our dedicated team behind the Mother Baby Biobank, which I established in 2020.3 The biobank has become a critical resource that has enabled us to answer pressing clinical questions informed by our experience treating neonates with congenital heart disease. My overarching goal is to improve survival rates and neurodevelopmental outcomes in this vulnerable and high-risk population.
To those who may feel daunted by the path of a physician-scientist, my advice is simple: make a little progress each day and find joy in the process as well as the outcomes.
Despite advances in neonatal care, the incidence of Bronchopulmonary Dysplasia (BPD) remains high among extreme preterm infants. The pathogenesis of BPD is multifactorial, with inflammation playing a central role. There is strong evidence that stem cell therapy reduces inflammatory changes and restores normal lung morphology in animal models of hyperoxia-induced lung injury. These therapeutic effects occur without significant engraftment of the stem cells in the host lung, suggesting more of a paracrine mechanism mediated by their secretome. In addition, there are multiple concerns with stem cell therapy which may be alleviated by administering only the effective vesicles instead of the cells themselves. Extracellular vesicles (EVs) are cell-derived components secreted by most eukaryotic cells. They can deliver their bioactive cargo (mRNAs, microRNAs, proteins, growth factors) to recipient cells, which makes them a potential therapeutic vehicle in many diseases, including BPD. The following review will highlight recent studies that investigate the effectiveness of EVs derived from stem cells in preventing or repairing injury in the preterm lung, and the potential mechanisms of action that have been proposed. Current limitations will also be discussed as well as suggestions for advancing the field and easing the transition towards clinical translation in evolving or established BPD.
Extracellular vesicles (EVs) derived from stem cells are a potential intervention for neonatal lung diseases. Their use might alleviate the safety concerns associated with stem cell therapy.
This review highlights recent studies that investigate the effectiveness of stem cell-derived EVs in preclinical models of bronchopulmonary dysplasia. It adds to the existing literature by elaborating on the challenges associated with EV research. It also provides suggestions to advance the field and ease the transition towards clinical applications.
Optimizing EV research could ultimately improve the quality of life of extreme preterm infants born at vulnerable stages of lung development.
We will never forget the day when we knew something was wrong with our son. One afternoon, our son experienced a bought of distress and uncontrollable crying. A few days after his agony started, while changing his diaper, we saw blood. We rushed him to his pediatrician and then a pediatric gastroenterologist. After diet changes, countless tests, and many failed interventions, our son was diagnosed with an extremely rare disease called Very Early Onset Inflammatory Bowel Disease (VEO-IBD). As parents already struggling with the normal challenges of raising a newborn, we were thoroughly overwhelmed managing our son’s disease in a world that seemed to know very little about it.
Very Early Onset Inflammatory Bowel Disease is so rare and individualized that no standard of care yet exists, and almost none of the interventions are approved for infants. After eliminating all dairy, prematurely ending breastfeeding, and moving exclusively to a prescription formula, we tried and failed multiple classes of medications, hoping each time that this medication would be the one that would ease our son’s suffering. Doctors are only now building a history of successful interventions to draw from, so treatment options come from very small studies from Very Early Onset Inflammatory Bowel Disease researchers and educated guesses. Treatment options generally ramp up in aggressiveness, which is hard enough for parents of a miserably sick infant to process and decide. Once these interventions fail, drug costs and insurance approval become major hurdles. This process of trial-and-error in treating Very Early Onset Inflammatory Bowel Disease patients is a nightmare. On a weekly or monthly basis, parents must make life-altering decisions with very little data for a patient too young to advocate for themselves.
Background: This study aimed to investigate the health-related quality of life (HRQoL) at 5 years of age of European children born very preterm across multi-dimensional outcomes by presence and severity of congenital anomalies.
Methods: The study used data from a European cohort of children born very preterm (<32 weeks of gestation) and followed up to 5 years of age (N = 3493). Multilevel Ordinary Least Squares (OLS) regression were used to explore the associations between the presence and severity of congenital anomalies.
Results: The mean total PedsQL™ GCS score for children with a mild congenital anomaly was lower than the respective value for children without a congenital anomaly by 3.7 points (p < 0.05), controlling for socioeconomic variables only; this effect was attenuated when accumulatively adjusting for perinatal characteristics (3.3 points (p < 0.05)) and neonatal morbidities (3.1 (p < 0.05)). The mean total PedsQL™ GCS scores for children who had a severe congenital anomaly were lower by 7.1 points (p < 0.001), 6.6 points (p < 0.001) and 6.0 points (p < 0.001) when accumulatively adjusting for socioeconomic, perinatal and neonatal variables, respectively.
Conclusion: This study revealed that the presence and severity of congenital anomalies are significant predictors of HRQoL outcomes in children born very preterm.
Impact: Children born very preterm with congenital anomalies experience poorer health-related quality of life (HRQoL) than their very preterm counterparts born without congenital anomalies. Increased severity of these anomalies compounds the negative impacts on HRQoL. Our findings can be used by stakeholders for clinical and planning purposes.
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