Poor Outcome In Children Research Articles

Late-onset neonatal sepsis was not associated with impaired neurodevelopmental outcome: Results from the EPICE/SHIPS-PT cohort.

To assess the impact of late-onset neonatal sepsis (LONS) on the cognitive and motor development of five-year-old children who were born very preterm (VPT). This study included 327 VPT children from the Portuguese EPICE/SHIPS cohort who attended the neurodevelopment assessment. Neuropsychological tests such as WPPSI-R, MABC-2 and NEPSY-II (language domain) were used to assess the children's cognitive and motor development. Statistical analysis was performed to compare the socio-demographic, clinical and neurodevelopment outcomes of VPT children with and without LONS. Regression analysis adjusted for confounding variables was performed when applicable. Underperformance in intelligence quotient and language development was similar regardless of a neonatal diagnosis of LONS. In contrast, VPT children with LONS had a higher risk of movement difficulties than those without LONS (p = 0.02). However, the association was lost after adjusting for confounders (β = -0.25; p > 0.05). LONS per se was not associated with the risk for poor long-term cognitive or motor outcomes in VPT children. Social-demographic and clinical characteristics assessed during the neonatal period and at the time of neurodevelopment assessment were similar between groups suggesting that social-related factors such as parents' educational level could have mitigated the LONS impact.

Child Health Needs and the Pediatric Rheumatology Workforce: 2020-2040.

The Pediatric Rheumatology (PRH) workforce supply in the United States does not meet the needs of children. Lack of timely access to PRH care is associated with poor outcomes for children with rheumatic diseases. This article is part of a Pediatrics supplement focused on anticipating the future pediatric subspecialty workforce supply. It draws on information in the literature, American Board of Pediatrics data, and findings from a model that estimates the future supply of pediatric subspecialists developed by the Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill, Strategic Modeling and Analysis Ltd., and the American Board of Pediatrics Foundation. PRH has a smaller workforce per capita of children than most other pediatric subspecialties. The model demonstrates that the clinical workforce equivalent of pediatric rheumatologists in 2020 was only 0.27 per 100 000 children, with a predicted increase to 0.47 by 2040. Although the model predicts a 72% increase in providers, this number remains inadequate to provide sufficient care given the number of children with rheumatic diseases, especially in the South and West regions. The likely reasons for the workforce shortage are multifactorial, including lack of awareness of the field, low salaries compared with most other medical specialties, concerns about working solo or in small group practices, and increasing provider retirement. Novel interventions are needed to increase the workforce size. The American College of Rheumatology has recognized the dire consequences of this shortage and has developed a workforce solutions initiative to tackle these problems.

Projecting the Future Pediatric Subspecialty Workforce: Summary and Recommendations.

This article summarizes the findings of a Pediatrics supplement addressing the United States workforce for 15 pediatric subspecialties. It includes results from a microsimulation model projecting supply through 2040; growth is forecasted to be uneven across the subspecialties with worsening geographic maldistribution. Although each subspecialty has unique characteristics, commonalities include (1) the changing demographics and healthcare needs of children, including mental health; (2) poor outcomes for children experiencing adverse social drivers of health, including racism; and (3) dependence on other subspecialties. Common healthcare delivery challenges include (1) physician shortages for some subspecialties; (2) misalignment between locations of training programs and subspecialists and areas of projected child population growth; (3) tension between increasing subsubspecialization to address rare diseases and general subspecialty care; (4) the need to expand clinical reach through collaboration with other physicians and advanced practice providers; (5) the lack of parity between Medicare, which funds much of adult care, and Medicaid, which funds over half of pediatric subspecialty care; and (6) low compensation of pediatric subspecialists compared with adult subspecialists. Overall, subspecialists identified the lack of a central authority to monitor and inform child healthcare provided by pediatric subspecialists as a challenge. Future research on the pediatric subspecialty workforce and the children it serves will be necessary to ensure these children's needs are met. Together, these articles provide overarching and subspecialty-specific recommendations to improve training, recruitment, and retention of a diverse workforce, implement innovative models of care, drive policy changes, and advise future research.

Risk Factors for Poor Outcomes in Children Hospitalized With Virus-associated Acute Lower Respiratory Infections: A Systematic Review and Meta-analysis.

Acute lower respiratory infection (ALRI) caused by respiratory viruses is among the most common causes of hospitalization and mortality in children. We aimed to identify risk factors for poor outcomes in children <5 years old hospitalized with ALRI caused by respiratory syncytial virus (RSV), influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We searched Embase, Medline and Global Health databases and included observational studies reporting risk factors for poor outcomes (defined as use of supplemental oxygen, mechanical ventilation, intensive care unit admission, prolonged hospital stay and mortality) published between January 2011 and January 2023. Two authors independently extracted data on study characteristics, outcomes and risk factors. Due to limited data, meta-analyses were only conducted for RSV-ALRI poor outcome risk factors using random effects model when there were at least 3 studies. We included 30 studies. For RSV-related ALRI, significant risk factors based on meta-analysis were: neurological disease [odds ratio (OR): 6.14; 95% confidence intervals (CIs): 2.39-15.77], Down's syndrome (5.43; 3.02-9.76), chronic lung disease (3.64; 1.31-10.09), immunocompromised status (3.41; 1.85-6.29), prematurity (2.98; 1.93-4.59), congenital heart disease (2.80; 1.84-4.24), underlying disease (2.45; 1.94-3.09), age <2 months (2.29; 1.78-2.94), age <6 months (2.08; 1.81-2.39), viral coinfection (2.01; 1.27-3.19), low birth weight (1.88; 1.19-2.95) and being underweight (1.80; 1.38-2.35). For influenza-related ALRI, chronic conditions and age 6-24 months were identified as risk factors for poor outcomes. Cardiovascular disease, immunosuppression, chronic kidney disease, diabetes and high blood pressure were reported as risk factors for mortality due to SARS-CoV-2 associated ALRI. These findings might contribute to the development of guidelines for prophylaxis and management of ALRI caused by RSV, influenza and SARS-CoV-2.

Screening for Food Insecurity in a Pediatric Diabetes Program: Provider and Parent/Guardian Perspectives.

Food insecurity (FI) is associated with poor health outcomes in children, and studies have shown higher FI among children with diabetes mellitus. This study assessed provider (N = 22, 35.5% response rate) and parent/guardian (N = 207, 14.6% response rate) perspectives toward FI screening in a pediatric diabetes program. Among 22 providers, most "rarely" (54.5%) or "never" (27.3%) screened for FI although all felt that screening was at least "slightly important." Barriers included lack of time (63.6%), not remembering to screen (59.1%), lack of knowledge about how to address positive screens (45.5%), and being unsure how to screen (40.9%). Among 186 parent/guardians, only 24.1% had been asked about FI at a pediatric medical appointment, but only 8.6% disliked the idea of being asked by a medical provider at endocrinology visits. To be effective and sustainable, FI screening must fit within the visit flow, and providers need education on how to address positive screens.

Paternal postnatal depression and parenting behaviours in the first year of life.

Paternal postnatal depression (PPD) symptomology has been positively associated with poorer outcomes for children. One mechanism by which PPD is thought to influence child outcomes is through parenting. The current study investigated the association between paternal postnatal depressive symptoms and parenting behaviours. Fathers (N = 213) with an infant (mean age = 7months, 46% female) between 2 and 12 months old were recruited through community and social media advertisements, as well as a paid survey recruitment website. Fathers completed a questionnaire on their symptoms of PPD and how they care for and raise their child (parental warmth, irritability, engagement in enrichment, play and safety behaviours). Fathers experiencing greater levels of PPD symptomatology self-reported higher irritability, lower warmth and fewer safe parenting behaviours but did not report lower enrichment or play with their infants. Overall, findings suggest that PPD symptomology may impact negatively on aspects of fathers' parenting behaviours. Further research using larger and more diverse samples is needed to assess the generalisability of these findings.

Nutritional Knowledge, WASH Practices of Mothers and Their Impact on the Nutritional Status of Children Aged 6–59 Months in Cumilla District, Bangladesh

Introduction: Child malnutrition is a pressing global public health issue, impacting both immediate health and future development. Adequate nutrition is a crucial aspect of public health, with maternal nutritional knowledge playing a vital role in ensuring optimal growth for children. Insufficient awareness about nutrition, even in households with sufficient resources, can result in poor outcomes for children.&#x0D; Aim: This study aimed to explore the contemporary status of maternal nutritional knowledge, water, sanitation, and hygiene (WASH) practices and their effect on the nutritional status of children aged 6–59 months in the Cumilla district of Bangladesh.&#x0D; Methods: A community-based cross-sectional study was carried out on 386 mother-child (6-59 months) pairs from 7 villages of the Cumilla district, Bangladesh. The study was designed to assess nutritional knowledge, WASH practices of mothers and nutritional status of their children using structured questionnaire and anthropometric measures. Chi square test was performed to investigate the association between maternal nutritional knowledge, WASH practices, and the nutritional status of children.&#x0D; Results: The study revealed, the level of nutritional knowledge was average (72.3%) among mothers. The prevalence of stunting, underweight, wasting and overweight were 38.6%, 16.9%, 11.9%, and 7.8% respectively. A strong relationship was found between nutritional knowledge, WASH practices of mothers and child’s stunting (p&lt;0.05) respectively. Maternal nutritional knowledge also had a strong association with underweight where female child was more prone to underweight than its male counterpart (p&lt;0.05). There was no significant association between maternal nutritional knowledge, WASH practices and wasting (p = 0.224, p = 0.328) respectively.&#x0D; Conclusion: The study revealed elevated rates of stunting and overweight in children compared to the national average, while underweight prevalence was lower and wasting prevalence was similar. Therefore, it is crucial to tackle social and cultural issues and implement effective strategies to enhance maternal nutritional knowledge and WASH practices to mitigate malnutrition in the rural areas of Bangladesh.

Psychosocial wellbeing, parental concerns, and familial impact of children with developmental coordination disorder

BackgroundDevelopmental Coordination Disorder (DCD) is a neurodevelopmental condition impacting motor skill acquisition and competence. While previous studies have identified adverse psychosocial outcomes in DCD, they are limited by small or population-screened, community-based samples. AimsTo understand the psychosocial difficulties, parental concerns, and familial impacts of childhood DCD in a large population-based sample. Methods and proceduresParents of 310 children aged 4 – 18 years with a diagnosis of DCD (or synonymous term) completed the Impact for DCD survey. Parent-rated measures of emotional problems, peer problems, and prosocial behaviour were compared to normative data. Parental concerns for the impact of DCD on participation, interaction, emotional well-being, and the family system were examined. Outcomes and resultsCompared to typically developing children, children with DCD were rated significantly higher for emotional and peer problems, and significantly lower for prosocial behaviours. Parents most commonly reported concerns for their child’s future and withdrawal from physical activity. The presence of one or more co-occurring disorders did not significantly influence outcomes. Conclusion and implicationsFindings highlight the poor psychosocial outcomes for children with DCD. Crucially, poor psychosocial outcomes were just as likely in those with a single diagnosis of DCD as those with DCD and multiple co-occurring diagnoses. Parents reported concerns for their child (i.e., non-participation and social withdrawal) that are not targeted in existing DCD intervention modalities and emphasised the impact of DCD on the whole family unit. What this paper addsThis paper presents data from the largest parent-reported survey of children with a known diagnosis of DCD (or synonymous labels). It highlights the significant impact of DCD on psychosocial outcomes in children across age groups. The children in this study were rated by their parents to have significantly higher levels of emotional and peer problems, and lower prosocial behaviours, than similarly aged Australian children without DCD. It also challenges the misconception that poor psychosocial outcomes in DCD are the result of co-occurring disorders, with outcomes observed to be as poor in children with a sole diagnosis of DCD in this sample. Furthermore, findings highlighted the significant worry and concern that parents with DCD face, particularly around their child’s participation and their emotional health. Finally, parents reported on the considerable impact that DCD had on their family unit, regularly causing worry and concern, influencing their choice of activities, and causing financial strain. These concerns and impacts are not addressed in current intervention models for DCD and highlight the need for support mechanisms moving forward.

Tei Index and its Relation to Outcome of Critically Ill Children on Continuous Renal Replacement Therapy.

To evaluate echocardiographic parameters, especially the Tei index as a predictor of outcome in critically ill children on continuous renal replacement therapy (CRRT). This cohort study included all critically ill patients admitted at the Pediatric intensive care unit (PICU) and underwent CRRT. Functional echocardiography and Pediatric Risk of Mortality Index (PRISM) III were used to evaluate the participants. Both the Tei index and the Vasoactive inotropic score (VIS) were estimated. The study included 35 patients with an age range of 6 mo to 14 y. The Tei indexes, VIS, and PRISM III were reported as predictors of mortality with a sensitivity of 88%, 83%, and 94% and a specificity of 73%, 79%, and 89% respectively. In survivors, the mean Tei index score, median VIS, and mean PRISM values were 0.44 ± 0.1, 3.8 (0-40), and 12.06 ± 3.35, respectively. However, in non-survivors, the mean Tei index, median VIS, and mean PRISM score were 0.59 ± 0.16, 0.60 (0-342.5), and 22.94 ± 8.93, respectively. The Tei index could be used as a predictor for poor outcomes in children receiving CRRT. It is correlated to the PRISM score and VIS.

Positive and adverse childhood experiences and mental health outcomes of children

ObjectiveResearchers and policymakers have identified adverse childhood experiences (ACEs) like abuse, neglect, and household dysfunction as a contributing factor to poor mental health outcomes for children. Positive childhood experiences (PCEs) like open family communication styles, having the ability to live and play in a safe, stable, and protective environment, having constructive opportunities for social engagement, and receiving mentorship from adults have been found to improve the mental health of children. PurposeThis paper explores the role of ACEs and PCEs on the mental health outcomes of children. MethodA sample of 22,628 children ages 6–17 from the National Survey of Children's Health (2017–2020) was used to explore the relationship between PCEs and ACEs and the mental health of children. Logistic regression analysis is used to model the effect of PCEs and ACEs on the odds of child mental health diagnoses. ResultsFindings indicate that with each additional ACE, there was a significant increase in the odds of reporting a MH condition (OR = 1.25, 95 % CI 1.09–1.43). Conversely, with each additional PCE, there is a significant decrease in the odds or reporting a MH condition (OR = 0.76, 95 % CI 0.68–0.84). There was also evidence that PCEs moderate the relationship between ACEs and reports of mental health conditions. When counts of ACEs are low, PCEs provide a protective effect on reports of mental health. But when the count of ACEs are high, children with higher numbers of PCEs have similar reports of mental health conditions. SummaryThis study provides information about the moderating effect of PCEs on the relationship between ACEs and child mental health diagnosis with the goal of informing policies and interventions focused on ameliorating the growing crisis of children's negative mental health and well-being. What is known?Adverse childhood events (ACEs) like abuse, neglect and household dysfunction are known to negatively impact the mental health and well-being of children. Positive childhood experiences (PCEs), on the other hand, can positively influence the mental health and well-being of children. What does this article add?This study examines the association between adverse and positive childhood experiences to understand how they impact the mental health outcomes of children ages 6–17. Findings indicate that when ACEs are lower, the impact of PCEs are positive, but when ACEs are higher, PCEs do not make much difference in reports of mental health problems.

Mothers' experiences of reducing family mealtime screen use in Australian households with young children.

Screen use at mealtimes is associated with poor dietary and psychosocial outcomes in children and is disproportionately prevalent among families of low socio-economic position (SEP). This study aimed to explore experiences of reducing mealtime screen use in mothers of low SEP with young children. Motivational interviews, conducted via Zoom or telephone, addressed barriers and facilitators to reducing mealtime screen use. Following motivational interviews, participants co-designed mealtime screen use reduction strategies and trialled these for 3-4 weeks. Follow-up semi-structured interviews then explored maternal experiences of implementing strategies, including successes and difficulties. Transcripts were analysed thematically. Australia. Fourteen mothers who had no university education and a child between six months and six years old. A range of strategies aimed to reduce mealtime screen use were co-designed. The most widely used strategies included changing mealtime location and parental modelling of expected behaviours. Experiences were influenced by mothers' levels of parenting self-efficacy and mealtime consistency, included changes to mealtime foods and an increased value of mealtimes. Experiences were reportedly easier, more beneficial and offered more opportunities for family communication, than anticipated. Change required considerable effort. However, effort decreased with consistency. The diverse strategies co-designed by mothers highlight the importance of understanding why families engage in mealtime screen use and providing tailored advice for reduction. Although promising themes were identified, in this motivated sample, changing established mealtime screen use habits still required substantial effort. Embedding screen-free mealtime messaging into nutrition promotion from the inception of eating will be important.

Associations between maternal stressful life events and child health outcomes in indigenous and non-indigenous groups in New Zealand

ABSTRACT Exposure to stressful life events (SLE) around the time of pregnancy is associated with adverse health outcomes for mothers and children. Previous New Zealand research found Indigenous Māori women are more likely to be exposed to SLE than non-Māori, and are exposed to a higher number of SLE. The consequences of this for ethnic inequities in child health outcomes are unknown. This paper examines the relationship between patterns of maternal SLE exposure with child health and development outcomes at age 3 years, for Indigenous and non-Indigenous children. We found most children had a stressful early life environment at least sometimes, but more than a quarter of Māori children had a mother experiencing multiple SLE on all occasions measured. We found a clear association between maternal experiences of SLE and disordered child sleep and development concerns. While not able to fully assess the contribution of maternal SLE to ethnic inequities in child health outcomes, we did clearly demonstrate that more Māori children have mothers exposed to multiple SLE, and that these maternal SLE are associated with poorer child outcomes. The impacts of chronic SLE exposure need to be better understood, especially given the large ethnic disparity in chronic SLE exposure.

Household income supplements in early childhood to reduce inequities in children's development

BackgroundEarly childhood interventions have the potential to reduce children's developmental inequities. We aimed to estimate the extent to which household income supplements for lower-income families in early childhood could close the gap in children's developmental outcomes and parental mental health. MethodsData were drawn from a nationally representative birth cohort, the Longitudinal Study of Australian Children (N = 5107), which commenced in 2004 and conducted follow-ups every two years. Exposure was annual household income (0–1 year). Outcomes were children's developmental outcomes, specifically social-emotional, physical functioning, and learning (bottom 15% versus top 85%) at 4–5 years, and an intermediate outcome, parental mental health (poor versus good) at 2–3 years. We modelled hypothetical interventions that provided a fixed-income supplement to lower-income families with a child aged 0–1 year. Considering varying eligibility scenarios and amounts motivated by actual policies in the Australian context, we estimated the risk of poor outcomes for eligible families under no intervention and the hypothetical intervention using marginal structural models. The reduction in risk under intervention relative to no intervention was estimated. ResultsA single hypothetical supplement of AU$26,000 (equivalent to ∼USD$17,350) provided to lower-income families (below AU$56,137 (∼USD$37,915) per annum) in a child's first year of life demonstrated an absolute reduction of 2.7%, 1.9% and 2.6% in the risk of poor social-emotional, physical functioning and learning outcomes in children, respectively (equivalent to relative reductions of 12%, 10% and 11%, respectively). The absolute reduction in risk of poor mental health in eligible parents was 1.0%, equivalent to a relative reduction of 7%. Benefits were similar across other income thresholds used to assess eligibility (range, AU$73,329-$99,864). ConclusionsHousehold income supplements provided to lower-income families may benefit children's development and parental mental health. This intervention should be considered within a social-ecological approach by stacking complementary interventions to eliminate developmental inequities.

Poverty and the wellbeing of children with sickle cell disease: The mediating role of parenting stress.

Living in poverty in the midst of caring for a child with sickle cell disease (SCD) presents with challenges that may be overwhelming for caregivers. Prior research has shown a relationship between poverty and poor outcomes in children; however, no study has investigated the mediating role of parenting stress on health-related quality of life (HRQOL) for such children. A total of 150 patients, ages 8-17years and their parents, were enrolled and completed measures of parenting stress (caregivers) and HRQOL (patients). Caregivers also completed a demographic information questionnaire, which was used to determine poverty status. The Sobel test was used to analyze the association between poverty and HRQOL by way of parenting stress. The series of linear regression results show poverty was a significant predictor for decreased HRQOL (B=-7.01, p=.05) among pediatric patients with SCD. Moreover, the regression coefficient measuring the indirect effect of the model measuring the mediating role of parenting stress was statistically significant (B=-1.05, p=.05). The current study found an association between poverty status and HRQOL scores by way of parenting stress. Findings highlight the need for appropriate resource allocation to caregivers in addition to pediatric patients living with SCD.

Respiratory culture growth and 3-years lung health outcomes in children with bronchopulmonary dysplasia and tracheostomies.

While bacteria identification on respiratory cultures is associated with poor short-term outcomes in children with bronchopulmonary dysplasia (BPD) and tracheostomies, the influence on longer-term respiratory support needs remains unknown. To determine if respiratory culture growth of pathogenic organisms is associated with ongoing need for respiratory support, decannulation, and death at 3 years posttracheostomy placement in children with BPD and tracheostomies. This single center, retrospective cohort study included infants and children with BPD and tracheostomies placed 2010-2018 and ≥1 respiratory culture obtained in 36 months posttracheostomy. Primary predictor was any pathogen identified on respiratory culture. Additional predictors were any Pseudomonas aeruginosa and chronic P. aeruginosa identification. Outcomes included continued use of respiratory support (e.g., oxygen, positive pressure), decannulation, and death at 3 years posttracheostomy. We used Poisson regression models to examine the relationship between respiratory organisms and outcomes, controlling for patient-level covariates and within-patient clustering. Among 170 children, 59.4% had a pathogen identified, 28.8% ever had P. aeruginosa, and 3.5% had chronic P. aeruginosa. At 3 years, 33.1% of alive children required ongoing respiratory support and 24.8% achieved decannulation; 18.9% were deceased. In adjusted analysis, any pathogen and P. aeruginosa were not associated with ongoing respiratory support or mortality. However, P. aeruginosa was associated with decreased decannulation probability (adjusted risk ratio 0.48, 95% CI 0.23-0.98). Chronic P. aeruginosa was associated with lower survival probability. Our findings suggest that respiratory pathogens including P. aeruginosa may not promote long-term respiratory dysfunction, but identification of P. aeruginosa may delay decannulation.

RNA-Binding Protein RBM5 Plays an Essential Role in Acute Myeloid Leukemia By Activating the Oncogenic Protein HOXA9

Acute myeloid leukemia (AML) represents a type of malignant hematological disease that indicates poor outcomes in children and adults. HOXA9 overexpression is observed in 50-70% of human AML and positively correlates with poor patient outcomes. Leukemia subtypes with hallmark overexpression of HOXA9 include but are not limited to those carrying KMT2A gene rearrangements (KMT2A-r), NPM1c mutations, NUP98-fusions and EZH2 mutation. Accumulating genetic evidence also indicates that HOXA9 dysregulation is sufficient and necessary for leukemic transformation, and loss of function of HOXA9 and downstream pathways consequently impaired leukemia maintenance. Although HOXA9 is not an ideal direct candidate for therapeutic interventions, uncovering the novel regulators of HOXA9 might elucidate the HOXA9 regulation mechanism that could be exploited to identify novel therapeutic targets in HOXA9-driven leukemias. In this study, we performed genome-wide CRISPR/Cas9 screens in the HOXA9-endogenous reporter acute leukemia cells and unbiasedly identified that candidate genes are significantly enriched in RNA binding and RNA splicing regulation. An RBP protein, RBM5, was among the top essential genes. Initially, RBM5 was reported as a tumor suppressor gene in lung cancer. Thus far, the function of the encoding protein RBM5 in blood cancer remained largely unknown. To further test how RBM5 expression might correlate with AML development, we analyzed the public RNA-seq data from the TCGA clinical cancer sample datasets, RBM5 is highly expressed in AML, indicating a plausible role in AML oncogenesis. Functional validation by two individual sgRNAs against different exons of RBM5 confirmed the selectively survival essential of RBM5 in AML cell lines. Ectopic expression of sgRNA-resistant RBM5 cDNA ultimately rescued the cellular phenotype upon RBM5 loss. We utilized an alternative loss-of-function approach, RNA interference (RNAi), to further examine the functional requirement of RBM5, Two independent shRNAs targeted RBM5 mRNA in three AML cells lines. RBM5 loss significantly impaired cell growth, reduced colony numbers and triggered notable myeloid differentiation. We further transplant MOLM13 cells targeted with shRBM5 into NSG mice, and observed that RBM5 shRNAs-treated animals lagged progressively more behind with much less splenomegaly and reduced leukemia cell infiltration in bone marrow, spleen, and peripheral blood compared to the wild-type control, suggesting that RBM5 is required for AML progression in vivo. More importantly, Suppression of RBM5 in primary AML cells significantly reduced colony numbers and induced myeloid differentiation, as demonstrated by the maturation markers CD11b and CD14. In addition, the domain dropout CRISPR screen revealed that the DNA-binding domain C2H2 is required for the gene function. Integrative analysis further suggested that HOXA9 promises the direct transcriptional target of RBM5 as demonstrated by functional rescue assay and HOXA9 partially restore the gene transcriptional defect in RBM5 null leukemia cells. In summary, our innovative research reported that a new RNA-binding protein, RBM5, is required for the survival of AML through non-canonical transcriptional regulation via a complex regulatory mechanism. These data support RBM5 as a promising AML therapeutic target in future studies.

Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial

ObjectiveTo investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness.DesignPhase 3b multicentre, double-blind, randomised placebo-controlled trial.SettingTwenty-one hospitals in the UK.ParticipantsChildren aged...

Auditory neural processing in children living with HIV uncovers underlying central nervous system dysfunction.

Central nervous system (CNS) damage from HIV infection or treatment can lead to developmental delays and poor educational outcomes in children living with HIV (CLWH). Early markers of central nervous system dysfunction are needed to target interventions and prevent life-long disability. The frequency following response (FFR) is an auditory electrophysiology test that can reflect the health of the central nervous system. In this study, we explore whether the FFR reveals auditory central nervous system dysfunction in CLWH. Cross-sectional analysis of an ongoing cohort study. Data were from the child's first visit in the study. The infectious disease center in Dar es Salaam, Tanzania. We collected the FFR from 151 CLWH and 151 HIV-negative children. To evoke the FFR, three speech syllabi (/da/, /ba/, /ga/) were played monaurally to the child's right ear. Response measures included neural timing (peak latencies), strength of frequency encoding (fundamental frequency and first formant amplitude), encoding consistency (inter-response consistency), and encoding precision (stimulus-to-response correlation). CLWH showed smaller first formant amplitudes ( P < 0.0001), weaker inter-response consistencies ( P < 0.0001) and smaller stimulus to response correlations ( P < 0.0001) than FFRs from HIV-negative children. These findings generalized across the three speech stimuli with moderately strong effect sizes (partial η2 ranged from 0.061 to 0.094). The FFR shows auditory central nervous system dysfunction in CLWH. Neural encoding of auditory stimuli was less robust, more variable, and less accurate. As the FFR is a passive and objective test, it may offer an effective way to assess and detect central nervous system function in CLWH.

Spectrum, Evolution, and Clinical Relationship of Magnetic Resonance Imaging in 31 Children with Febrile Infection-Related Epilepsy Syndrome.

Describing spectrum, evolution, and clinical relationship of brain magnetic resonance imaging (MRI) findings in a large case series of children with febrile infection-related epilepsy syndrome (FIRES). This retrospective study included 31 children with FIRES. Clinical data and MRI findings of the brain were evaluated. Poor clinical outcome was defined as severe disability, persistent vegetative state or stupor, very low intelligence quotient (<80), or death (modified Rankin scale 4-6 and Glasgow Outcome Score 1-3). Seventeen (54.8%) children with FIRES showed no abnormalities in the initial MRI, whereas 28 (90.3%) children showed MRI abnormalities at follow-up. The most frequent abnormalities were brain atrophy (74.2%) and T2/fluid-attenuated inversion recovery changes (64.5%), mostly hippocampal (45.2%). Generalized brain atrophy was the most frequent type of atrophy (58%). The earliest atrophy was recorded 9 days after the onset of disease. It progressed even beyond the acute phase in most children (51.6%). The exploratory data analysis revealed nominal significance between all MRI abnormalities considered together and poor outcome (p = 0.049) and between generalized brain atrophy and anesthesia (p = 0.024). After adjustment for multiple testing, the p-values were not significant. The outcome in four (12.9%) children was not poor despite generalized brain atrophy. In contrast to the uniform clinical course, MRI demonstrated a broad spectrum of findings. Initially, these were mostly normal and therefore indicative of FIRES but then changed rapidly and were mostly progressive despite the stable chronic course. The cause may be ongoing disease, treatment intensity, or both. Future studies should focus on what process underlies the onset and the progression of brain atrophy. However, brain atrophy was not always related to poor outcomes in children despite FIRES.

Clinical features and risk factors analysis for poor outcomes of severe community-acquired pneumonia in children: a nomogram prediction model.

Pneumonia remains the leading cause of death among children aged 1-59 months. The early prediction of poor outcomes (PO) is of critical concern. This study aimed to explore the risk factors relating to PO in severe community-acquired pneumonia (SCAP) and build a PO-predictive nomogram model for children with SCAP. We retrospectively identified 300 Chinese pediatric patients diagnosed with SCAP who were hospitalized in the Affiliated Hospital of Southwest Medical University from August 1, 2018, to October 31, 2021. Children were divided into the PO and the non-PO groups. The occurrence of PO was designated as the dependent variable. Univariate and multivariate logistic regression analyses were used to identify the risk factors of PO. A nomogram model was constructed from the multivariate logistic regression analysis and internally validated for model discrimination and calibration. The performance of the nomogram was estimated using the concordance index (C-index). According to the efficacy evaluation criteria, 56 of 300 children demonstrated PO. The multivariate logistic regression analysis resulted in the following independent risk factors for PO: co-morbidity (OR: 8.032, 95% CI: 3.556-18.140, P < 0.0001), requiring invasive mechanical ventilation (IMV) (OR: 7.081, 95% CI: 2.250-22.282, P = 0.001), and ALB < 35 g/L (OR: 3.203, 95% CI: 1.151-8.912, P = 0.026). Results of the internal validation confirmed that the model provided good discrimination (concordance index [C-index], 0.876 [95% CI: 0.828-0.925]). The calibration plots in the nomogram model were of high quality. The nomogram facilitated accurate prediction of PO in children diagnosed with SCAP and could be helpful for clinical decision-making.