Risk Stratification Of Children Research Articles

The Role of Ultrasound in Pediatric Skull Fractures: Determination of Fracture and Optic Nerve Sheath Diameter Measurements.

The aim of the present study was to determine the accuracy of point-of-care ultrasound (POCUS) for detecting skull fractures and to evaluate sonographic measurements of optic nerve sheath diameter (ONSD) and ONSD/eyeball vertical diameter (EVD) ratios in children with head trauma. Children who presented with local signs of head trauma and underwent cranial computed tomography (CT) were enrolled. The suspected area was examined by POCUS to identify a skull fracture, and then the ONSD at 3 mm posterior to the globe and the EVD were measured. Ratios of ONSD measurement at 3 mm/EVD were reported. All ONSD measurements and ratios were calculated from cranial CT images. There were 112 children enrolled in the study. The sensitivity and specificity of POCUS for skull fractures was 93.7% (95% confidence interval [CI], 82.8-98.6) and 96.8% (95% CI, 89.1-99.6), whereas the positive predictive value was 95.7% (95% CI, 85.1-98.8), and the negative predictive value was 95.3% (95% CI, 87.3-98.4). There was high agreement between POCUS and CT for identifying skull fractures (κ, 0.90 [±0.04]). In the group without elevated intracranial pressure findings on CT, patients with space-occupying lesions (SOLs) had higher sonographic ONSD measurements and ratios (P < 0.001) compared with cases without SOLs. When used with clinical decision rules to minimize the risk for clinically important traumatic brain injury, POCUS seems to be a promising tool to detect skull fractures and calculate ONSD measurements and rates to predict the risk for SOLs and perform further risk stratification of children with minor head trauma.

MicroRNA-146a-5p and microRNA-210-3p Correlate with T Regulatory Cells Frequency and Predict Asthma Severity in Egyptian Pediatric Population.

Severe bronchial asthma (BA) affects 5-10% of children, which imposes socioeconomic burden. Therefore, it is crucial to identify biomarkers for risk stratification in children with BA. T regulatory cells (Tregs) play a balancing role in allergic response regulation. We aimed to investigate the relationship between Treg, miR-210-3p, and miR-146a-5p in relation to asthma phenotypes in search of novel biomarkers of disease severity. This study included 50 children with BA classified into Group 1 (n = 25) children with mild to moderate asthma and Group 2 (n = 25) children with severe asthma. In addition to 26 control subjects. Flow cytometry was used to detect Tregs. Plasma miR-210-3p and miR-146a levels were determined using quantitative real-time PCR. Patients' FEV1 (Forced Expiratory Volume in the first second) was measured. miR-210-3p level correlated negatively with Treg frequency (r = -0.828, P < 0.001) and FEV1 (r = -0.621, P < 0.001). The level of miR-146a-5p positively correlated positively with Treg% (r = 0.303, P = 0.032). ROC curve analysis revealed that miR-210-3p was the most sensitive biomarker of severity, with the area under curve (AUC) = 0.923, 96% sensitivity, and 60% specificity. According to multivariate analysis, miR-210-3p is an independent risk factor for BA severity [OR =3.119, P = 0.030], while miR-146a-5p is a protective factor [OR =0.811, P = 0.049]. Treg frequency is linked to FEV1, miR-146a-5p and miR-210-3p in childhood BA. Upregulation of miR-210-3p is a sensitive biomarker and an independent risk factor for BA severity in Egyptian children.

Type I and Ir pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry.

Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood. Type I PPB is a purely cystic lesion that has a microscopic population of primitive small cells with or without rhabdomyoblastic features and may progress to type II or III PPB, whereas type Ir lacks primitive small cells. Children with suspected PPB were enrolled in the International PPB/DICER1 Registry. Pathology was centrally reviewed, and follow-up was ascertained annually. Between 2006 and 2022, 205 children had centrally reviewed type I or Ir PPB; 39% of children with type I and 5% of children with type Ir PPB received chemotherapy. Outcomes were favorable, although 11 children (nine with type I and two with type Ir PPB) experienced progression to type II/III (n=8) or regrowth of type I PPB at the surgical site (n=3), none of whom received chemotherapy before progression. Age and cyst size in combination were more suitable than either factor alone in predicting whether a particular lesion was type I or Ir PPB. For young children with type I PPB, outcomes are favorable, but complete resection is indicated because of the risk for progression. Chemotherapy may be useful in a subset of children at increased risk for recurrence/progression. Efforts to risk stratify children with type I PPB to optimize outcomes while reducing treatment-related side effects are underway.

Prognostic Importance of Cytogenetic Subgroups in Relapse Risk Stratification in Children and Young Adults with First Relapsed B-ALL: A Children's Oncology Group Study AALL1331

Prognostic Importance of Cytogenetic Subgroups in Relapse Risk Stratification in Children and Young Adults with First Relapsed B-ALL: A Children's Oncology Group Study AALL1331

Performance of host-response biomarkers to risk-stratify children with pneumonia in Bhutan

Pneumonia is the leading cause of post-neonatal death amongst children under five years of age; however, there is no simple triage tool to identify children at risk of progressing to severe and fatal disease. Such a tool could assist for early referral and prioritization of care to improve outcomes and enhance allocation of scarce resources. We compared the performance of inflammatory and endothelial activation markers in addition to clinical signs or scoring scales to risk-stratify children hospitalized with pneumonia at the national referral hospital of Bhutan with the goal of predicting clinical outcome. Of 118 children, 31 evolved to a poor prognosis, defined as either mortality, admission in the paediatric intensive care unit, requirement of chest drainage or requirement of more than five days of oxygen therapy. Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) was the best performing biomarker and performed better than clinical parameters. sTREM-1 levels upon admission had good predictive accuracy to identify children with pneumonia at risk of poor prognosis. Our findings confirm that immune and endothelial activation markers could be proactively used at first encounter as risk-stratification and clinical decision-making tools in children with pneumonia; however, further external validation is needed.

Vascular biomarkers in the prevention of childhood cardiovascular risk: From concept to clinical implementation.

Vascular biomarkers allow for non-invasive assessment of vascular structure and function and have been shown to be surrogates for cardiovascular (CV) outcome in adults. They reflect the cumulative risk of a plethora of single CV risk factors, such as obesity and hypertension, on the arterial wall. The process of atherosclerosis oftentimes has its origin in childhood and tracks into adulthood. Obesity-related CV risk in childhood is a main determinant of manifest CV disease and adverse outcome in adulthood. To date, prevention strategies are directed toward the detection and reduction of CV disease in adulthood. This review updates and puts into perspective the potential use of vascular biomarkers in children. With reference to the concept of early vascular aging in adults, it elaborates on the role of vascular biomarkers for CV risk stratification in children. The concept of primordial vascular aging implies that young children be screened for vascular health, in an attempt to timely detect subclinical atherosclerosis and initiate treatment strategies to reverse vascular damage in a period of life with high probability for risk regression. The evidence for the validity of macro- and microvascular candidate biomarkers as screening tools of CV risk in children is reviewed, and limitations as well as remaining research gaps are highlighted. Furthermore, an overview on the effects of exercise treatment on vascular biomarkers is given. Vascular biomarkers susceptible to lifestyle or drug treatment have the potential to qualify as monitoring tools to guide clinicians. This review discusses evidence for vascular biomarkers to optimize screening of childhood CV risk from initial concepts to potential future clinical implementation in cardiovascular prevention.

A New and Cost-Effective Approach to Risk Stratification for Children with Precursor B-Cell Acute Lymphoblastic Leukemia Based on Competing Outcomes

Background: Acute lymphoblastic leukemia (ALL) is a malignancy of the white blood cells characterized by its rapid and aggressive progress that needs immediate treatment. ALL could affect both adults and children. Various patient- and disease-related factors may be involved in ALL patients’ prognosis. Therefore, it is critical to identify important risk factors related to the competing outcomes of patients with ALL. Objectives: This study aimed to stratify the risk of outcomes of children with precursor B-cell ALL using demographic characteristics, laboratory characteristics, and extramedullary diseases. To achieve this goal, we used the best competing risks model to make an appropriate decision for children's treatment according to this classification. Methods: In this retrospective cohort study, 393 patients with ALL were included. ALL with B cell origins (CD20, CD19, CD10, and CD22 positive markers) was differentiated using flow cytometry. Complete remission was defined by a lymphoblast count of less than 5% in the bone marrow, presence of no blasts in cerebrospinal fluid (CSF), as well as complete disappearance of clinical symptoms. Patients with ALL were treated based on Berlin-Frankfurt-Münster (BFM). Competing outcomes were first-relapse and non-relapse mortality, respectively. Risk factors affecting competing outcomes were assessed based on a fully specified sub-distribution model. Results: Five-year estimates for overall survival and event free survival were 75% (95% CI: 69 - 79%) and 71% (95% CI: 66 - 75%), respectively. Five-year incidence rates for first-relapse and non-relapse mortality in children were 11.4% (95% CI: 8.32 - 15.16%) and 17.6% (95% CI: 13.98 - 21.67%), respectively. Moreover, according to the results, children with WBC &gt; 50000, hemoglobin 8, and tumor lysis syndrome for the first-relapse outcome, and children with central nervous system (CNS) involvement and tumor lysis syndrome for the non-relapse mortality (NRM) outcome were considered as high-risk groups. Conclusions: We found that extramedullary diseases could have a crucial role in the risk stratification of children with precursor B-cell ALL. Therefore, for a targeted and effective treatment of high-risk children, in addition to chemotherapy, using appropriate PI3K pathway inhibitors, JAK2 pathway inhibitors, and antibody-based immunotherapy is recommended to reduce minimal residual disease and, consequently, mortality rate.

Immune and endothelial activation markers and risk stratification of childhood pneumonia in Uganda: A secondary analysis of a prospective cohort study.

BackgroundDespite the global burden of pneumonia, reliable triage tools to identify children in low-resource settings at risk of severe and fatal respiratory tract infection are lacking. This study assessed the ability of circulating host markers of immune and endothelial activation quantified at presentation, relative to currently used clinical measures of disease severity, to identify children with pneumonia who are at risk of death.Methods and findingsWe conducted a secondary analysis of a prospective cohort study of children aged 2 to 59 months presenting to the Jinja Regional Hospital in Jinja, Uganda between February 2012 and August 2013, who met the Integrated Management of Childhood Illness (IMCI) diagnostic criteria for pneumonia. Circulating plasma markers of immune (IL-6, IL-8, CXCL-10/IP-10, CHI3L1, sTNFR1, and sTREM-1) and endothelial (sVCAM-1, sICAM-1, Angpt-1, Angpt-2, and sFlt-1) activation measured at hospital presentation were compared to lactate, respiratory rate, oxygen saturation, procalcitonin (PCT), and C-reactive protein (CRP) with a primary outcome of predicting 48-hour mortality. Of 805 children with IMCI pneumonia, 616 had severe pneumonia. Compared to 10 other immune and endothelial activation markers, sTREM-1 levels at presentation had the best predictive accuracy in identifying 48-hour mortality for children with pneumonia (AUROC 0.885, 95% CI 0.841 to 0.928; p = 0.03 to p < 0.001) and severe pneumonia (AUROC 0.870, 95% CI 0.824 to 0.916; p = 0.04 to p < 0.001). sTREM-1 was more strongly associated with 48-hour mortality than lactate (AUROC 0.745, 95% CI 0.664 to 0.826; p < 0.001), respiratory rate (AUROC 0.615, 95% CI 0.528 to 0.702; p < 0.001), oxygen saturation (AUROC 0.685, 95% CI 0.594 to 0.776; p = 0.002), PCT (AUROC 0.650, 95% CI 0.566 to 0.734; p < 0.001), and CRP (AUROC 0.562, 95% CI 0.472 to 0.653; p < 0.001) in cases of pneumonia and severe pneumonia. The main limitation of this study was the unavailability of radiographic imaging.ConclusionsIn this cohort of Ugandan children, sTREM-1 measured at hospital presentation was a significantly better indicator of 48-hour mortality risk than other common approaches to risk stratify children with pneumonia. Measuring sTREM-1 at clinical presentation may improve the early triage, management, and outcome of children with pneumonia at risk of death.Trial registrationThe trial was registered at clinicaltrial.gov (NCT 04726826).

Soluble Urokinase-Type Plasminogen Activator Receptor as a Prognostic Marker of Ugandan Children at Risk of Severe and Fatal Malaria.

Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk-stratify children with malaria. Plasma suPAR levels were determined in consecutive febrile children with malaria at presentation to hospital in Jinja, Uganda. We evaluated the accuracy of suPAR in predicting in-hospital mortality, and whether suPAR could improve a validated clinical scoring system (Lambaréné Organ Dysfunction Score [LODS]). Of the 1226 children with malaria, 39 (3.2%) died. suPAR concentrations at presentation were significantly higher in children who went on to die than in those who survived (P < .0001). suPAR levels were associated with disease severity (LODS: 0 vs 1, P = .001; 1 vs 2, P < .001; 2 vs 3, 0 vs 2, 1 vs 3, and 0 vs 3, P < .0001). suPAR concentrations were excellent predictors of in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.92 [95% confidence interval {CI}, .91-.94]). The prognostic accuracy of LODS (AUROC, 0.93 [95% CI, .91-.94]) was improved when suPAR was added (AUROC, 0.97 [95% CI, .96-.98]; P < .0001). Measuring suPAR at presentation can identify children at risk of severe and fatal malaria. Adding suPAR to clinical scores could improve the recognition and triage of children at risk of death. suPAR can be detected with a point-of-care test and can now be evaluated in prospective trials.

A Scoping Review of Galectin-3 as a Biomarker of Cardiovascular Diseases in Pediatric Populations.

Galectin-3 as a cardiac biomarker has proven to be a significant prognostic tool in adults. However, it has not yet been established in the pediatric population as a biomarker in daily clinical practice. The aim of the study was to summarize the current knowledge on galectin-3 as a biomarker in children with cardiac conditions by reviewing the literature. Bibliographic databases such as PubMed, Web of Science and Embase were searched, and consequently twelve articles met the inclusion criteria. Supplemental handsearching of references delivered one additional source. These prospective studies concerning galectin-3 as a cardiac biomarker present analyses performed in cohorts composed of healthy children and children with cardiovascular diseases. The results, despite being based on small cohort studies, inform that galectin-3 could serve as a potential biomarker in cardiovascular risk stratification in children with heart failure, arrhythmia, Kawasaki disease or in patients undergoing cardiac surgery. The evidence for the usefulness of galectin-3 in the assessment of such pathologies as idiopathic dilated cardiomyopathy, coarctation of the aorta, functionally univentricular heart or tetralogy of Fallot were not completely confirmed. Galectin-3 seems to be a promising biomarker; however, there is a need for further research to establish its use in daily clinical practice.

133 Quantitative Imaging Measurements Marginally Improve Risk Prediction for Children with Mild Traumatic Brain Injuries and Intracranial Injuries

INTRODUCTION: The KIIDS-TBI model was recently developed and externally validated in two large, multicenter populations to risk-stratify children with mild traumatic brain injuries (mTBI) and intracranial injuries. However, the KIIDS-TBI model only evaluates the presence/absence of imaging findings, rather than quantitative measures (e.g., hematoma size). METHODS: We included children &lt;18 years who presented to one of five centers within 24 hours of TBI, had GCS scores of 13-15, and had intracranial injuries on neuroimaging. The dataset was split into training (75%) and test (25%) cohorts. We used generalized linear models (GLM) and recursive partitioning (RP) to predict the composite outcome of neurosurgery, intubation &gt;24 hours due to TBI, or death due to TBI. Each model’s performance was compared to the KIIDS-TBI model across three decision-making risk cutoffs (&lt;1%, &lt;3%, and &lt;5% predicted risk). RESULTS: There were 1,126 children included in the training and 374 in the test dataset. The RP model included epidural hematoma size, amount of skull fracture depression, amount of midline shift, and extra-axial hematoma size. The GLM model included these imaging variables and added clinical predictors, such as GCS Score. The GLM (76-90%) and RP (79-87%) models showed similar specificity across the three risk cutoffs in the test dataset, but the GLM model had higher sensitivity (89-96% for GLM; 89% for RP). By comparison, the KIIDS-TBI model had slightly higher sensitivity (93-100%) but lower specificity (27-82%) across the three risk cutoffs. CONCLUSION: Despite having obvious face value in many aspects of neurosurgical decision-making, quantitative imaging measures only marginally improved efforts to identify low risk patients in a large dataset of children with mTBI and intracranial injuries. Given the tradeoff between improved specificity but decreased sensitivity, these results do not support the addition of quantitative imaging measures to the KIIDS-TBI tool.

Dyslipidemia Diagnosis and Treatment: Risk Stratification in Children and Adolescents.

Dyslipidemias or dyslipoproteinemias are quantitative changes in total cholesterol concentration, respective fractions, or triglycerides in the plasma. Evidence supported that dyslipidemia in childhood is associated with atherosclerosis in adulthood, and early identification and treatment potentially reduce cardiovascular risk in adulthood, which is the principal cause of morbidity and mortality in developed countries. Dyslipidemias can result from primary lipoprotein metabolism changes due to different genetic causes (primary dyslipidemias) or as a consequence of exogenous factors or other pathologies (secondary dyslipidemias). Therefore, the combined dyslipidemias result from the association of important epigenetic and environmental influences with risk factors for cardiovascular disease. The criterion for lipid metabolism screening at young ages is not widely accepted and possibly follows a universal or directed screening strategy. Additionally, little is known about its long-term effects or possible risk-benefit despite the growing tendency to start pharmacological therapy. Therefore, this study aimed to review the available bibliography on dyslipidemia in pediatric age to present a practical and structured approach to dyslipidemia that focuses on screening, risk stratification for atherosclerotic disease, and therapeutic approach.

Myocardial Deformation Imaging by Speckle-Tracking Echocardiography for Assessment of Cardiotoxicity in Children during and after Chemotherapy: A Systematic Review and Meta-Analysis

Children with cancer and childhood cancer survivors (CCS) are at risk for developing chemotherapy-induced cardiomyopathy. Myocardial deformation imaging has shown potential in the early detection of subclinical myocardial damage with implications on therapeutic interventions and improvement of outcomes. The aim of this study was to perform a systemic review and meta-analysis of literature on the assessment of left ventricular and right ventricular myocardial deformation by speckle-tracking echocardiography at rest and during stress in children with cancer during and in survivors after chemotherapy. A systematic review was performed through searching MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Central Register of Controlled Trials, and Scopus. Search hedges were created to cover the concepts of childhood cancer, chemotherapy, radiotherapy, anthracycline, cardiotoxicity, speckle-tracking, myocardial strain, and myocardial deformation. Two independent investigators reviewed the eligibility of articles for inclusion. The weighted mean difference in ventricular strain between pre- and postchemotherapy treatment and that between long-term CCS and healthy subjects were estimated using random-effect models with 95% CIs. Heterogeneity and publication bias were assessed using I2 statistics and the Egger test, respectively. Of the total of 8,703 records initially identified, 42 studies with a total of 5,430 children with cancer were included. Of these 42 studies that showed heterogeneities, nine assessed early myocardial injury during chemotherapy, 30 assessed late myocardial injury after chemotherapy with no publication bias, and three studied myocardial mechanics during stress. The main findings were as follows: (1) left ventricular systolic deformation is impaired in children with cancer during the initial treatment phase and among long-term CCS, while data on changes in right ventricular deformation are limited and inconclusive; (2) the predictive value of early reduction of myocardial strain imaging in forecasting subsequent development of cardiotoxicity is unknown, as it has not been studied; (3) limited data suggest the possibility of impaired left ventricular contractile mechanics during stress in CCS; and (4) cumulative anthracycline dose and chest-directed radiotherapy are consistently identified as factors associated with impaired myocardial deformation. Myocardial strain imaging by speckle-tracking echocardiography unveils early evidence of myocardial injury in children with cancer and long-term CCS. To support its adoption for clinical use, more data are required for the better understating of myocardial deformation parameters in the risk stratification of children with cancer and prediction of development of cardiomyopathy among CCS.

Risk Factors for Severe COVID-19 in Children: A Systematic Review and Meta-Analysis.

BackgroundCoronavirus disease 2019 (COVID-19) has been the most important global issue since December 2019. Although the clinical course of COVID-19 is known to be milder in children than in adults, associated hospitalizations among children have increased since the emergence of contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the achievement of a high vaccination rate in adults. Considering these global and domestic situations, we believe that risk stratification in children with COVID-19 is urgently needed for decision making regarding hospitalization priority in children infected with SARS-CoV-2 and vaccination priority against COVID-19.MethodsThis systematic review and meta-analysis was performed by comprehensively searching the PubMed, EMBASE, Scopus and KoreaMed databases through August 25, 2021. The criteria for enrollment were “severe COVID-19” as poor outcomes (intensive care unit admission, invasive mechanical ventilation, and/or death) and underlying comorbidities before SARS-CoV-2 infection.ResultsAmong 872 screened studies, 17 articles were included in the systematic review, and 10 articles were included in the meta-analysis. Neonate (risk ratio [RR], 2.69; 95% confidence interval [CI], 1.83–3.97), prematurity in young infants (RR, 2.00; 95% CI, 1.63–2.46), obesity (RR, 1.43; 95% CI, 1.24–1.64), diabetes (RR, 2.26; 95% CI, 1.95–2.62), chronic lung disease (RR, 2.62; 95% CI, 1.71–4.00), heart disease (RR, 1.82; 95% CI, 1.58–2.09), neurologic disease (RR, 1.18; 95% CI, 1.05–1.33), and immunocompromised status (RR, 1.44; 95% CI, 1.01–2.04) were significant risk factors for severe COVID-19 in children. In the subgroup analysis, age younger than 3 months (RR, 0.26; 95% CI, 0.11–0.66), asthma (RR, 1.08; 95% CI, 0.98–1.20), and neurodevelopmental disorders (RR, 0.88; 95% CI, 0.75–1.04) were not risk factors for severe COVID-19.ConclusionChildren with comorbidities such as obesity, diabetes, heart disease, chronic lung diseases other than asthma, seizure disorders, and an immunocompromised status had a high prevalence of severe COVID-19. Neonate and premature infants had a high risk of severe COVID-19. Defining the high-risk group for severe COVID-19 could help to guide hospital admission and priority for vaccination against SARS-CoV-2.

Surfactant protein D is a biomarker of influenza-related pediatric lung injury.

Biomarkers that can risk-stratify children with influenza virus lower respiratory infection may identify patients for targeted intervention. Early elevation of alveolar-related proteins in the bloodstream in these patients could indicate more severe lung damage portending worse outcomes. We used a mouse model of human influenza infection and evaluated relationships between lung pathophysiology and surfactant protein D (SP-D), SP-A, and Club cell protein 16 (CC16). We then measured SP-A, SP-D, and CC16 levels in plasma samples from 94 children with influenza-associated acute respiratory failure (PICFLU cohort), excluding children with underlying conditions explaining disease severity. We tested for associations between levels of circulating proteins and disease severity including the diagnosis of acute respiratory distress syndrome (ARDS), mechanical ventilator, intensive care unit and hospital days, and hospital mortality. Circulating SP-D showed a greater increase than SP-A and CC16 in mice with increased alveolar-vascular permeability following influenza infection. In the PICFLU cohort, SP-D was associated with moderate-severe ARDS diagnosis (p = 0.01) and with mechanical ventilator (r = 0.45, p = 0.002), ICU (r = 0.44, p = 0.002), and hospital days (r = 0.37, p = 0.001) in influenza-infected children without bacterial coinfection. Levels of SP-D were lower in children with secondary bacterial pneumonia (p = 0.01) and not associated with outcomes. CC16 and SP-A levels did not differ with bacterial coinfection and were not consistently associated with severe outcomes. SP-D has potential as an early circulating biomarker reflecting a degree of lung damage caused directly by influenza virus infection in children. Secondary bacterial pneumonia alters SP-D biomarker performance.

Islet Autoantibody Type-Specific Titer Thresholds Improve Stratification of Risk of Progression to Type 1 Diabetes in Children.

To use islet autoantibody titers to improve the estimation of future type 1 diabetes risk in children. Prospective cohort studies in Finland, Germany, Sweden, and the U.S. followed 24,662 children at increased genetic or familial risk to develop islet autoimmunity and diabetes. For 1,604 children with confirmed positivity, titers of autoantibodies against insulin (IAA), GAD antibodies (GADA), and insulinoma-associated antigen 2 (IA-2A) were harmonized for diabetes risk analyses. Survival analysis from time of confirmed positivity revealed markedly different 5-year diabetes risks associated with IAA (n = 909), GADA (n = 1,076), and IA-2A (n = 714), when stratified by quartiles of titer, ranging from 19% (GADA 1st quartile) to 60% (IA-2A 4th quartile). The minimum titer associated with a maximum difference in 5-year risk differed for each autoantibody, corresponding to the 58.6th, 52.4th, and 10.2nd percentile of children specifically positive for each of IAA, GADA, and IA-2A, respectively. Using these autoantibody type-specific titer thresholds in the 1,481 children with all autoantibodies tested, the 5-year risk conferred by single (n = 954) and multiple (n = 527) autoantibodies could be stratified from 6 to 75% (P < 0.0001). The thresholds effectively identified children with a ≥50% 5-year risk when considering age-specific autoantibody screening (57-65% positive predictive value and 56-74% sensitivity for ages 1-5 years). Multivariable analysis confirmed the significance of associations between the three autoantibody titers and diabetes risk, informing a childhood risk surveillance strategy. This study defined islet autoantibody type-specific titer thresholds that significantly improved type 1 diabetes risk stratification in children.

Total Psoas Muscle Area as a Marker for Sarcopenia Is Related to Outcome in Children With Neuroblastoma.

Background: Sarcopenia describes a generalized loss of skeletal muscle mass, strength, or function. Determined by measuring the total psoas muscle area (tPMA) on cross-sectional imaging, sarcopenia is an independent marker for poor post-surgical outcomes in adults and children. Children with cancer are at high risk for sarcopenia due to immobility, chemotherapy, and cachexia. We hypothesize that sarcopenic children with neuroblastoma are at higher risk for poor post-operative outcomes.Patients and Methods: Retrospective analysis of children with neuroblastoma ages 1–15 years who were treated at our hospital from 2008 to 2016 with follow-up through March 2021. Psoas muscle area (PMA) was measured from cross-sectional images, using computed tomography (CT) and magnetic resonance imaging (MRI) scans at lumbar disc levels L3-4 and L4-5. tPMA is the sum of the left and right PMA. Z-scores were calculated using age- and gender-specific reference values. Sarcopenia was defined as a tPMA z-score below −2. A correlation of tPMA z-scores and sarcopenia with clinical variables and outcome was performed.Results: One hundred and sixty-four children with workup for neuroblastoma were identified, and 101 children fulfilled inclusion criteria for further analysis, with a mean age of 3.92 years (SD 2.71 years). Mean tPMA z-score at L4-5 was −2.37 (SD 1.02). Correlation of tPMA z-score at L4-5 with weight-for-age z-score was moderate (r = 0.54; 95% CI, 0.38, 0.66). No association between sarcopenia and short-term outcome was observed. Sarcopenia had a sensitivity of 0.82 (95% CI, 0.62–0.93) and a specificity of 0.48 (95% CI 0.36–0.61) in predicting 5-year survival. In a multiple regression analysis, pre-operative sarcopenia, pre-operative chemotherapy in the NB2004 high-risk group, unfavorable tumor histology, and age at diagnosis were associated with 5-year survival after surgery, with hazard ratios of 4.18 (95% CI 1.01–17.26), 2.46 (95% CI 1.02–5.92), 2.39 (95% CI 1.03–5.54), and 1.01 (95% CI 1.00–1.03), respectively.Conclusion: In this study, the majority of children had low tPMA z-scores and sarcopenia was a risk factor for decreased 5-year survival in children with neuroblastoma. Therefore, we suggest measuring the tPMA from pre-surgical cross-sectional imaging as a biomarker for additional risk stratification in children with neuroblastoma.

Impact of the 2017 American Academy of Pediatrics' Clinical Practice Guideline on the Identification and Risk Stratification of Youth at Increased Cardiovascular Disease Risk.

The updated clinical practice guideline (CPG) published by the American Academy of Pediatrics in 2017 introduced significant changes to the diagnostic and evaluative approach towards children with elevated blood pressure. The goals of this review were to summarize the current evidence regarding the impact of the new CPG on the identification and risk stratification of children at increased cardiovascular disease risk. Universally, the new CPG definitions of abnormal blood pressure led to more children classified as having a hypertensive blood pressure when compared with alternative definitions. Youth who moved to a higher blood pressure stage with the CPG typically had worse cardiometabolic profiles and more comorbidites. The association of CPG-defined hypertension and concurrent intermediate cardiovascular disease outcomes such as left ventricular hypertrophy and increased pulse wave velocity remains unclear; however, longitudinal data suggests an improved identification of those at greatest risk for adult cardiovascular disease with the CPG definitions. The majority of studies reviewed used blood pressure from one encounter, not replicate blood pressures from multiple visits, to define an abnormal or hypertensive blood pressure. Therefore, future studies investigating the prevalence of confirmed hypertension and the association between confirmed hypertension and outcomes are needed to optimally characterize the performance of the new CPG on identifying children at cardiovascular disease risk.

Relative Risk Analysis of Liver-related Adverse Drug Reactions in Children Based on China’s National Spontaneous Reporting System

To compare the risk of liver-related adverse drug reactions (ADRs) in children and adults. A case/non-case analysis on spontaneous reports based on the China National Adverse Drug Reactions Monitoring System database were conducted, focusing on events of liver-related ADRs in children younger than 14years of age. Both the relative risk of liver-related ADRs in children vs entire population and the risk stratification in children were expressed as a measure of disproportionality using the reporting odds ratio (ROR). There were 1206 cases of pediatric liver-related ADRs identified from 2012 to 2016, accounting for 2.82% of the entire population. The greatest ROR values in children from 0 to 14years vs the entire population were observed for analgesics (3.97, 95% CI 3.27-4.81), respiratory (2.60, 95% CI 1.04-6.43), antineoplastic (2.29, 95% CI 2.02-2.58), immunomodulatory (1.91, 95% CI 1.44-2.53), and antimicrobial agents (1.47, 95% CI 1.33-1.63). Notably, infants aged 0-1years showed significantly greater risk (3.14, 95% CI 2.85-3.48) of liver-related ADRs than the other age groups of children. For infants, analgesics (3.21, 95% CI 2.20-4.66) and antimicrobials (3.15, 95% CI 2.50-3.97) agents were found to have the greatest adjusted RORs than other drug categories. The highest RORs were found for meropenem, amoxicillin, fluconazole, vancomycin, cefaclor, and ceftazidime in the antimicrobial agents for infants. Children are sensitive to liver-related ADRs caused by several specific drug categories, and infants are the most sensitive.

Pediatric acute kidney injury: new advances in the last decade.

Pediatric acute kidney injury (AKI) is a frequently missed complication. AKI has a significant impact on both short- and long-term outcomes in children. Within the last decade, there have been major landmark developments in this field of critical care pediatric nephrology. The topic was searched by two independent researchers using Google Scholar and PubMed and related studies published in the last 10 years. The terms used for the search were ‘pediatric acute kidney injury,’ ‘pediatric acute renal failure,’ ‘pediatric dialysis,’ ‘biomarkers,’ ‘nephrotoxins,’ ‘nephrotoxicity in children,’ and ‘pediatric critical care nephrology.’ We found that AKI is common in critically ill neonates and children. Among the various definitions, the Kidney Disease: Improving Global Outcomes (KDIGO) definition is most commonly used. In addition, it is imperative to risk stratify sick children at admission in the hospital to predict AKI and worse outcomes as this aids in early management. There are now major landmark trials that describe the epidemiology, prevention, and management guidelines in this field and health care professionals need to be aware they should diagnose AKI early. Overall, this review highlights the landmark studies in the last decade and shows that early diagnosis and management of AKI in ‘at risk’ children can improve outcomes.