Risk Stratification Of Children Research Articles

RIKADA Study Reveals Risk Factors in Pediatric Primary Cardiomyopathy.

BackgroundCardiomyopathies are heterogeneous diseases with clinical presentations varying from asymptomatic to life‐threatening events, including severe heart failure and sudden cardiac death. The role of underlying genetic and disease‐modulating factors in children and adolescents is relatively unknown. In this prospective study, in‐depth phenotypic and genetic characterization of pediatric patients with primary cardiomyopathy and their first‐degree family members (FMs) was performed. Outcome was assessed to identify clinical risk factors.Methods and ResultsSixty index patients with primary cardiomyopathy (median age: 7.8 years) and 124 FMs were enrolled in the RIKADA (Risk Stratification in Children and Adolescents with Primary Cardiomyopathy) study. Family screening included cardiac workup and genetic testing. Using cardiologic screening, we identified 17 FMs with cardiomyopathies and 30 FMs with suspected cardiomyopathies. Adverse events appeared in 32% of index patients and were more common in those with lower body surface area (P=0.019), increased NT‐proBNP (N‐terminal pro–brain natriuretic peptide; P<0.001), and left ventricular dysfunction (P<0.001) and dilatation (P=0.005). The worst prognosis was observed in dilated and restrictive cardiomyopathies. Genetic variants of interest were detected in patients (79%) and FMs (67%). In all 15 families with at least 1 FM with cardiomyopathy, we found a variant of interest in the index patient. Increased number of variants of interest per patient was associated with adverse events (P=0.021). Late gadolinium enhancement was related to positive genotypes in patients (P=0.041).ConclusionsLower body surface area, increased NT‐proBNP, left ventricular dysfunction or dilatation, late gadolinium enhancement, and increased number of variants of interest were associated with adverse outcome and should be considered for risk assessment in pediatric primary cardiomyopathies.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/. Unique identifier: NCT03572569.

Improving Risk Stratification for Children With Pneumonia: The Journey Continues

Improving Risk Stratification for Children With Pneumonia: The Journey Continues

Mortality Predictive Scores for Community-Acquired Pneumonia in Children.

The use of severity score for the staging of pneumonias has emerged as a necessity for the physician caring for this disease. Although there are several established prognostic scoring systems for community-acquired pneumonia in adults, the availability for children are scarce. Recently, scoring system for risk stratification of children with pneumonia were developed in low- and middle-income countries. They use clinical variables that represent known risk factors for severe outcomes of respiratory illness in children, such as hypoxemia, chest indrawing, refusal to feed, malnutrition, age, and stage of HIV disease among others factors. Although they showed good discriminating power and are very useful in low-resource settings, the characteristics of the patients, the local epidemiology of concurrent diseases, the social conditions, and the facilities of the hospitals make them not applicable to developed countries. A new prognostic scale for estimating mortality based on the modified PIRO scale used in adults with pneumonia can be useful for developed countries. Although several scoring systems for the estimation of mortality in childhood CAP were developed in the last years, most of them come from developing countries and the results are not applicable to patients with pneumonia in developed countries. Prospective studies applying scores adapted to the reality of the developed countries are needed.

EMR Adaptations to Support the Identification and Risk Stratification of Children with Special Health Care Needs in the Medical Home.

Introduction Children with special health care needs (CSHCN) are a high risk population with complex medical issues and needs. It is challenging to care for them in a busy, pediatric practice without understanding how many exist and how best to allocate resources. EMRs can be adapted todevelop registries and stratify patients to promote population health management. Methods Adaptations were made to the EMR in September 2013 to capture CSHCN and the associated risk level during well-child visits prospectively. All physicians were trained on the definition of CSHCN and on risk stratification levels 1, 2, 3A and 3B. An analysis using one-way ANOVA for children ages 0-21, seen between September 1, 2011 and August 31, 2015, who were identified and stratified after September 2013, was conducted to determine utilization patterns on hospital admissions, emergency department (ED), subspecialty, and primary care visits. Results A total of 4687 CSHCN were identified during the study period. Of the CSHCN, 45% were Level 1, 41% Level 2, 7% 3A and 7% 3B. There were significant differences in utilization across the tiers of CSHCN with the highest level of stratification (3B) demonstrating the most hospital admissions and primary care visits. Level 3B and level 3A (unstable) had significantly more ED visits. Additionally, as tiers increased from level 1 to 3B there was an increase in subspecialty provider utilization (p < 0.0001). Discussion The EMR adaptations developed for CSHCN identified the expected number of CSHCN and predicted utilization patterns across primary, subspecialty, ED and in-patient care.

Therapeutics for Inflammatory Bowel Diseases in Children and Adolescents: A Focus on Biologics and an Individualized Treatment Paradigm.

Pharmacologic treatment of children and adolescents with inflammatory bowel diseases (IBD) [Crohn's disease and ulcerative colitis] requires consideration of disease and medication effects on growth and nutrition, the importance of durability of biologics, and concerns for long-term sequelae of disease and therapies. Achieving early remission in children with Crohn's disease correlates with improved outcomes and therefore allows a window of opportunity for maximizing growth. Thus, there is a great need to treat children and adolescents with the right drug at the right time while achieving adequate exposure. Improved understanding of disease phenotypes, disease natural history, and risk stratification will play a critical role in treatment selection for children, particularly as more therapeutic options become available. Here we summarize data supporting newer concepts of treating the individual child with IBD through targeted early biologic treatment, including utilization of therapeutic drug monitoring to optimize treatment effects and the use of early antitumor necrosis factor (TNF)-α therapies to mitigate long-term sequelae of the disease. Recent inception cohort studies provide important data regarding the risk stratification of children and adolescents with IBD, which support a move toward a personalized therapeutic approach to IBD in children and adolescents.

Oxygenation Index in the First 24 Hours after the Diagnosis of Acute Respiratory Distress Syndrome as a Surrogate Metric for Risk Stratification in Children.

BackgroundThe diagnosis of pediatric acute respiratory distress syndrome (PARDS) is a pragmatic decision based on the degree of hypoxia at the time of onset. We aimed to determine whether reclassification using oxygenation metrics 24 hours after diagnosis could provide prognostic ability for outcomes in PARDS.MethodsTwo hundred and eighty-eight pediatric patients admitted between January 1, 2010 and January 30, 2017, who met the inclusion criteria for PARDS were retrospectively analyzed. Reclassification based on data measured 24 hours after diagnosis was compared with the initial classification, and changes in pressure parameters and oxygenation were investigated for their prognostic value with respect to mortality.ResultsPARDS severity varied widely in the first 24 hours; 52.4% of patients showed an improvement, 35.4% showed no change, and 12.2% either showed progression of PARDS or died. Multivariate analysis revealed that mortality risk significantly increased for the severe group, based on classification using metrics collected 24 hours after diagnosis (adjusted odds ratio, 26.84; 95% confidence interval [CI], 3.43 to 209.89; P=0.002). Compared to changes in pressure variables (peak inspiratory pressure and driving pressure), changes in oxygenation (arterial partial pressure of oxygen to fraction of inspired oxygen) over the first 24 hours showed statistically better discriminative power for mortality (area under the receiver operating characteristic curve, 0.701; 95% CI, 0.636 to 0.766; P<0.001).ConclusionsImplementation of reclassification based on oxygenation metrics 24 hours after diagnosis effectively stratified outcomes in PARDS. Progress within the first 24 hours was significantly associated with outcomes in PARDS, and oxygenation response was the most discernable surrogate metric for mortality.

Autonomous Ca2+ Oscillations Reflect Oncogenic BCR-Signaling in Multiple B-Cell Malignancies and Are Essential for Survival and Proliferation

Background: Nuclear factor of activated T cells (NFAT) factors regulate activation and Ca2+ signaling in B-cells. Store-operated Ca2+ entry (SOCE) is regulated by Orai1 and Stim1 and upstream of NFAT. We previously reported on the observation of autonomous oscillatory Ca2+ signal activity in BCR-ABL1-driven B-ALL. Autonomous Ca2+ oscillations may provide oncogenic survival signals to B-ALL cells, however their significance and mechanism remained unclear.Results: Here we found that autonomous Ca2+ oscillations are common across multiple subtypes of B-cell lineage ALL and mature B-cell lymphoma and reflect downstream survival and proliferation signals from oncogenic BCR-signaling or oncogenes that mimic active BCR-signaling (e.g. ABL1-kinase fusions, CD79B mutation, EBV-encoded oncoprotein LMP2A, RAS-pathway lesions). By contrast, multiple myeloma and Hodgkin's lymphoma that lack BCR-expression and function also lack Ca2+ oscillations (Figure, top panel). As Orai1 and Stim1/2 are essential SOCE-effector genes, we performed genetic experiments to test the impact of Cre-mediated deletion of Orai1 and Stim1/2 in BCR-ABL1 and NRASG12D-dependent models of B-ALL. Inducible deletion of Orai1 or Stim1/2 not only abrogated SOCE but also autonomous Ca2+ oscillations. Signal amplitudes of residual autonomous Ca2+ oscillations were significantly reduced (P < 0.0001; Figure, bottom panel). Further, deletion of either Orai1 or Stim1/2 induced cell death and abrogated colony-forming capacity in both models of B-ALL. In agreement with these findings, NFATc1 no longer translocated to the nucleus upon Cre-mediated ablation of Orai1 or Stim1/2 induced, which reflected functional inactivation of NFATc1. These results demonstrated that Orai1- and Stim1/2-mediated SOCE signaling and autonomous Ca2+ oscillations are critical in BCR-ABL1 and NRASG12D-dependent B-ALL. A NFAT-calcineurin association inhibitor, INCA-6, was tested for its ability to suppress NFATc1 and autonomous Ca2+ signaling in patient-derived xenograft (PDX) models of B-ALL, mantle cell lymphoma and DLBCL. Treatment with INCA-6 suppressed survival and proliferation signals in all six PDX of B-ALL, mantle cell lymphoma and DLBCL but not multiple myeloma cells. Unlike myeloma cells, B-ALL, mantle cell and DLBCL cells expressed a functional (pre-)BCR. These findings suggest that the SOCE-NFAT pathway is linked to Ca2+ signaling downstream of a functional BCR- or oncogenic BCR-mimics. Furthermore, to determine whether high expression levels of ORAI1, STIM1, STIM2 and NFATC1 represents a biomarker of clinical outcome for patients with B-ALL, we segregated patients from two clinical trials (Children's Oncology Group P9906 (n=207) and Eastern Cooperative Oncology Group (E2993; n=215)) into two groups on the basis of higher or lower than median expression levels of ORAI1, STIM1, STIM2 and NFATC1 at the time of diagnosis. Higher than median expression levels of each of these four genes at the time of diagnosis predicted shorter overall and relapse-free survival (P < 0.02 or lower for each of these genes). These findings identify SOCE-NFAT signal as a novel biomarker with potential use in risk stratification of children and adults with B-ALL.Conclusions: We identified Orai1 and Stim1 as central mediators of SOCE. Most BCR-dependent B-cell malignancies are driven by oncogenic BCR-signals, which result in autonomous Ca2+ oscillations. While the significance of autonomous Ca2+-oscillations remains unclear, deletion of Orai1 and Stim1/2 resulted in a complete loss of Ca2+ oscillations, loss of NFATc1-activation and cell death. We conclude that previously unrecognized Ca2+-oscillations downstream of oncogenic BCR-signaling are required for survival and proliferation of B-ALL and B-cell lymphoma cells. Pharmacological inhibition of SOCE (Orai1 and Stim1/2) or NFATC1 (e.g. INCA-6) represents a selective strategy to disrupt autonomous Ca2+ oscillations and oncogenic BCR-signaling in a broad range of B-cell malignancies. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Perinatal Nutritional Reprogramming of the Epigenome Promotes Subsequent Development of Nonalcoholic Steatohepatitis.

With the epidemic of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common pediatric liver disease. The influence of a perinatal obesity‐inducing diet (OID) on the development and progression of NAFLD in offspring is important but incompletely studied. Hence, we fed breeding pairs of C57BL/6J mice during gestation and lactation (perinatally) either chow or an OID rich in fat, fructose, and cholesterol (FFC). The offspring were weaned to either chow or an FFC diet, generating four groups: perinatal (p)Chow‐Chow, pChow‐FFC, pFFC‐Chow, and pFFC‐FFC. Mice were sacrificed at 10 weeks of age. We examined the whole‐liver transcriptome by RNA sequencing (RNA‐seq) and whole‐liver genome methylation by reduced representation bisulfite sequencing (RRBS). Our results indicated that the pFFC‐FFC mice had a significant increase in hepatic steatosis, injury, inflammation, and fibrosis, as assessed histologically and biochemically. We identified 189 genes that were differentially expressed and methylated in the pFFC‐FFC mice versus the pChow‐FFC mice. Gene set enrichment analysis identified hepatic fibrosis/hepatic stellate cell activation as the top canonical pathway, suggesting that the differential DNA methylation events in the mice exposed to the FFC diet perinatally were associated with a profibrogenic transcriptome. To verify that this finding was consistent with perinatal nutritional reprogramming of the methylome, we exposed pFFC‐Chow mice to an FFC diet in adulthood. These mice developed significant hepatic steatosis, injury, inflammation, and more importantly fibrosis when compared to the appropriate controls. Conclusion: Perinatal exposure to an OID primes the immature liver for an accentuated fibrosing nonalcoholic steatohepatitis (NASH) phenotype, likely through nutritional reprogramming of the offspring methylome. These data have potential clinical implications for monitoring children of obese mothers and risk stratification of children with NAFLD.

Obesity, Blood Pressure, and Retinal Vessels: A Meta-analysis.

Retinal vessel imaging is a noninvasive diagnostic tool used to evaluate cardiovascular risk. Childhood obesity and elevated blood pressure (BP) are associated with retinal microvascular alterations. To systematically review and meta-analyze associations between obesity, BP, and physical activity with retinal vessel diameters in children. We conducted a literature search through the databases of PubMed, Embase, Ovid, Web of Science, and the Cochrane Register of Controlled Trials. School- and population-based cross-sectional data. General information, study design, participants, exposure, and outcomes. A total of 1751 studies were found, and 30 full-text articles were analyzed for eligibility. Twenty-two articles (18 865 children and adolescents) were used for further assessment and reflection. Eleven articles were finally included in the meta-analysis. We found that a higher BMI is associated with narrower retinal arteriolar (pooled estimate effect size -0.37 [95% confidence interval (CI): -0.50 to -0.24]) and wider venular diameters (0.35 [95% CI: 0.07 to 0.63]). Systolic and diastolic BP are associated with retinal arteriolar narrowing (systolic BP: -0.63 [95% CI: -0.92 to -0.34]; diastolic BP: -0.60 [95% CI -0.95 to -0.25]). Increased physical activity and fitness are associated with favorable retinal vessel diameters. Long-term studies are needed to substantiate the prognostic relevance of retinal vessel diameters for cardiovascular risk in children. Our results indicate that childhood obesity, BP, and physical inactivity are associated with retinal microvascular abnormalities. Retinal vessel diameters seem to be sensitive microvascular biomarkers for cardiovascular risk stratification in children.

Factors Associated With Pneumonia Severity in Children: A Systematic Review.

Community-acquired pneumonia in children is associated with significant morbidity and mortality; however, data are limited in predicting which children will have negative outcomes, including clinical deterioration, severe disease, or development of complications. The Pediatric Infectious Diseases Society/Infectious Diseases Society of America (PIDS/IDSA) pediatric pneumonia guideline includes criteria that were modified from adult criteria and define pneumonia severity to assist with resource allocation and site-of-care decision-making. However, the PIDS/IDSA criteria have not been formally developed or validated in children. Definitions for mild, moderate, and severe pneumonia also vary across the literature, further complicating the development of standardized severity criteria. This systematic review summarizes (1) the current state of the evidence for defining and predicting pneumonia severity in children as well as (2) emerging evidence focused on risk stratification of children with pneumonia.

Assigning Cytomegalovirus Status in Children Awaiting Organ Transplant: Viral Shedding, CMV-Specific T Cells, and CD27-CD28-CD4+ T Cells.

Passive antibodies, maternal or transfusion-acquired, make serologic determination of pretransplant cytomegalovirus (CMV) status unreliable. We evaluated 3 assays unaffected by passive antibodies, in assignment of CMV infection status in children awaiting solid organ transplant and in controls: (1) CMV nucleic acid amplification testing (NAAT), (2) quantification of CMV-specific CD4+ T cells, and (3) quantification of CD27-CD28-CD4+ T cells. Our results highlight that CMV NAAT, from urine and oropharynx, is useful in confirming positive CMV status. Detection of CMV-specific CD4+ T cells was sensitive and specific in children >18 months but was less sensitive in children <12 months. CD27-CD28-CD4+ T cells are not likely useful in CMV risk stratification in children.

Suspected Pediatric Influenza Risk-Stratification Algorithm: A Clinical Decision Tool.

Influenza causes significant annual burden among children. Current guidelines recommend empiric treatment for a broadly defined group of children at high risk for influenza complications, resulting in overtreatment or costly viral testing. This study creates an algorithm for clinicians to risk stratify children with influenza-like illness (ILI) according to likelihood of influenza infection. A retrospective analysis was performed on 818 children seen in the emergency department from November 2012 to April 2013 for ILI. We reviewed medical records for symptoms, influenza risk factors, and viral assay results. Classification and regression tree analyses were performed separately for children older and younger than 2 years. In children younger than 2 years, populations likely to test positive were those with an influenza-positive contact, unimmunized children, and those presenting in high-incidence influenza periods. In this subgroup, immunized patients in low-incidence seasons and those with absence of cough are low risk for influenza infection. For children 2 years and older, high-risk populations were unimmunized children, those presenting in high-incidence influenza periods and those with myalgia or absence of diarrhea. These risk-stratification analyses were summarized into Suspected Pediatric Influenza Risk-Stratification Algorithm (SPIRA). For those in whom influenza infection is likely, clinicians may consider empiric treatment. Conversely, patients whom SPIRA identifies as unlikely to be infected with influenza are candidates for viral testing and targeted treatment. In assessing children with ILI, SPIRA aids clinicians in determining who to test versus treat empirically, saving children from costly viral testing or unnecessary antiviral exposure.

A prognostic tool to predict outcomes in children undergoing the Norwood operation

ObjectivesTo create and validate a prediction model to assess outcomes associated with the Norwood operation. MethodsThe public-use dataset from a multicenter, prospective, randomized single-ventricle reconstruction trial was used to create this novel prediction tool. A Bayesian lasso logistic regression model was used for variable selection. We used a hierarchical framework by representing discrete probability models with continuous latent variables that depended on the risk factors for a particular patient. Bayesian conditional probit regression and Markov chain Monte Carlo simulations were then used to estimate the effects of the predictors on the means of these latent variables to create a score function for each of the study outcomes. We also devised a method to calculate the risk of outcomes associated with the Norwood operation before the actual heart operation. The 2 study outcomes evaluated were in-hospital mortality and composite poor outcome. ResultsThe training dataset used 520 patients to generate the prediction model. The model included patient demographics, baseline characteristics, cardiac diagnosis, operation details, site volume, and surgeon experience. An online calculator for the tool can be accessed at https://soipredictiontool.shinyapps.io/NorwoodScoreApp/. Model validation was performed on 520 observations using an internal 10-fold cross-validation approach. The prediction model had an area under the curve of 0.77 for mortality and 0.72 for composite poor outcome on the validation dataset. ConclusionsOur new prognostic tool is a promising first step in creating real-time risk stratification in children undergoing a Norwood operation; this tool will be beneficial for the purposes of benchmarking, family counseling, and research.

Predictive Formulas To Improve The Interpretation Of Cardiorespiratory Fitness In Children

Adequate reference values for cardiopulmonary exercise testing (CPET) is crucial for accurate interpretation and prognostic purposes for children with a chronic disease. Current reference values in healthy children have been developed using heterogeneous exercise protocols and often incomplete adjustment for body size. PURPOSE: To update current reference values from CPET and provide new reference values for several parameters previously unstudied in children using a prospectively recruited cohort of healthy children. METHODS: In this cross-sectional multicenter study, we prospectively recruited 269 healthy children (♂=107; ♀=162) between the ages of 12-17 years old (14.8 ± 1.5) in local schools. We measured height, weight, waist circumference, pubertal development and fat free mass (FFM) and performed a symptom-limited CPET (Vmax Encore Metabolic Cart, Sensormedic, San Diego, CA) on an electronically-braked ergocycle using a progressive ramp protocol. Reference values and Z score were computed by testing several regressions models for each CPET measurement. Variation around the predicted mean was modeled to account for heteroscedasticity and residual association with growth-related parameters was assessed. RESULTS: Using currently published reference values, up to 31.2% of children were classified as having abnormal CPET results despite being free of chronic disease. Our weighted non-linear parametric modeling allowed more precise and well-adjustted Z scores and percentiles limits. The table shows a selection of our predicting equations as well as the percentage of children below the 3rd percentile. Selection of prediction equations for malesTable: No title available.CONCLUSION: The use of weighted non-linear regression model resulted in a decreased false-positive rate. These updated and new reference values provide an accurate lower limit of normal thus improving their value for prognostic and risk-stratification in children with chronic diseases.

24 Hour urine metabolic differences between solitary and multiple stone formers: Results of the Collaboration on Urolithiasis in Pediatrics (CUP) working group

Specific factors associated with the risk of developing pediatric urinary stone disease remain unclear, especially those that may be associated with recurrent stone disease. We compared the results of 24-hurine collections in children with a solitary stone episode to those with multiple stone episodes to determine if there is a difference that may be associated with multiple stone formation in children. A multi-institutional retrospective analysis was completed to assess 24-hurinary metabolic profiles in children with urolithiasis aged 2-18 years old. Differences in mean urine collections between the two groups were assessed using chi-square tests to test the associations among gender, stone type, and multiple stone status, as well as multivariate analyses using general linear models. We analyzed 142 solitary stone patients and 136 multiplestone patients from four centers were included. Multiple stone patients were older than solitary stone patients (mean 13.4±3.6 years vs.12±3.9 years, p=0.002). Females were more likely to have multiple stones (58% vs. 39%, p=0.002). BMI was not associated with multiple stones (p=0.8467). Multiple stone formers had lower urine volumes, although this did not reach statistical significance when compared with solitary stone formation (20.4mL/kg/day±11.5 vs. 22.9±13.0, p=0.0880). Higher values for super-saturation of calcium oxalate were associated with multiple stone disease in univariate (p=0.0485) and multivariate analysis (p=0.0469) (Figure). Centers located in the Southeast of the United States saw a higher proportion of children with multiple stones (Tennessee 62.7%, Virginia 44.4%, Oregon 31.6%, Michigan 27.3%, p<0.0001). In a large multi-institutional retrospective analysis we found that multiple stone disease was associated with higher super-saturations of calcium oxalate. Many urinary parameters changed with patient age, highlighting that the values should be interpreted with respect to patient age. The inability to comment on follow-up because of the nature of our dataset is a limitation of this study. Multiple stone disease in children is associated with higher super-saturation calcium oxalate, while lower urinary volume may also be associated with multiple stones; however, further study is required. Early metabolic evaluation may help risk stratify children likely to form multiple stones.

IBD: Risk stratification in children with Crohn's disease.

IBD: Risk stratification in children with Crohn's disease.

Anomalous Coronary Arteries and Myocardial Bridges: Risk Stratification in Children Using Novel Cardiac Catheterization Techniques.

The evaluation of the vast majority of children with anomalous aortic origin of a coronary artery (AAOCA) and/or myocardial bridges is performed with non-invasive testing. However, a subset of these patients may benefit from invasive testing for risk stratification. All patients included in the Coronary Anomalies Program (CAP) at Texas Children's Hospital who underwent cardiac catheterization were included. Techniques included selective coronary angiograms (SCA), intravascular ultrasound (IVUS), and fractional flow reserve (FFR) measurements with provocative testing using adenosine and/or dobutamine infusions. Out of the 131 patients followed by the CAP between 12/12-4/16, 8 (6%) patients underwent 9 cath investigations at median age 13.1 (2.6-18.7) years and median weight 49.5 (11.4-142.7) kg. Six patients presented with cardiac signs/symptoms. Four patients had myocardial bridges of the left anterior descending (LAD) coronary artery, 2 patients had isolated AAOCA, and 2 patients had an anomalous left coronary artery (LCA) with an intramyocardial course of the LAD. SCA was performed in all patients. FFR was positive in 4/6 patients: IVUS showed >70% intraluminal narrowing in 3/5 patients. One patient had hemodynamic instability that reversed with catheter removal from the coronary ostium. Based on the catheterization data obtained, findings were reassuring in three patients, surgery was performed in three patients, and two patients are being medically managed/restricted from competitive sports. In our small cohort of patients, we demonstrated that IVUS and FFR can safely be performed in children and may help to risk stratify some patients with AAOCA and myocardial bridges.

Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration

Comparative assessment of treatment results in paediatric hepatoblastoma trials has been hampered by small patient numbers and the use of multiple disparate staging systems by the four major trial groups. To address this challenge, we formed a global coalition, the Children's Hepatic tumors International Collaboration (CHIC), with the aim of creating a common approach to staging and risk stratification in this rare cancer. The CHIC steering committee-consisting of leadership from the four major cooperative trial groups (the International Childhood Liver Tumours Strategy Group, Children's Oncology Group, the German Society for Paediatric Oncology and Haematology, and the Japanese Study Group for Paediatric Liver Tumours)-created a shared international database that includes comprehensive data from 1605 children treated in eight multicentre hepatoblastoma trials over 25 years. Diagnostic factors found to be most prognostic on initial analysis were PRETreatment EXTent of disease (PRETEXT) group; age younger than 3 years, 3-7 years, and 8 years or older; α fetoprotein (AFP) concentration of 100 ng/mL or lower and 101-1000 ng/mL; and the PRETEXT annotation factors metastatic disease (M), macrovascular involvement of all hepatic veins (V) or portal bifurcation (P), contiguous extrahepatic tumour (E), multifocal tumour (F), and spontaneous rupture (R). We defined five clinically relevant backbone groups on the basis of established prognostic factors: PRETEXT I/II, PRETEXT III, PRETEXT IV, metastatic disease, and AFP concentration of 100 ng/mL or lower at diagnosis. We then carried the additional factors into a hierarchical backwards elimination multivariable analysis and used the results to create a new international staging system. Within each backbone group, we identified constellations of factors that were most predictive of outcome in that group. The robustness of candidate models was then interrogated using the bootstrapping procedure. Using the clinically established PRETEXT groups I, II, III, and IV as our stems, we created risk stratification trees based on 5 year event-free survival and clinical applicability. We defined and adopted four risk groups: very low, low, intermediate, and high. We have created a unified global approach to risk stratification in children with hepatoblastoma on the basis of rigorous statistical interrogation of what is, to the best of our knowledge, the largest dataset ever assembled for this rare paediatric tumour. This achievement provides the structural framework for further collaboration and prospective international cooperative study, such as the Paediatric Hepatic International Tumour Trial (PHITT). European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission (grant number 261474); Children's Oncology Group CureSearch grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research; and Swiss Cancer Research grant.

Value of the electrocardiographic strain pattern in children and adolescents with end stage renal disease

BackgroundAmong several electrocardiographic LVH criteria, LVH strain pattern was implicated as the strongest marker of cardiovascular adverse outcomes in general population and hypertensives. ObjectiveThe aim of this work is to detect the prevalence, clinical relevance and determinants of ECG strain pattern presence in children and adolescents with ESRD. MethodsThe study was performed at Zagazig University Hospital during the year 2012–2013. The studied patients with ESRD undergoing hemodialysis (24 males and 26 females) were categorized into three groups according to ECG. All patients were subjected to laboratory investigations (albumin, fasting lipids, renal function, serum creatinine, K+ serum, Ca2+ serum, phosphorus serum, alkaline phosphatase [ALP] serum, hemoglobin, pro BNP and parathormone), standard 12 leads surface ECG, and echocardiography (ECHO). ResultsECG strain was the most prevalent electrocardiographic pattern among the studied patients (42% versus 26% normal ECG and 32% ECG LVH without strain) who clinically have more ischemic chest pain (81% in group III versus 23.1% in group I and 43.8% in group III, p=0.003) and systolic hypertension (p=0.006). The prolonged disease duration (p=0.005), increased LVM (p=0.007), higher TC (p<0.01), lower Hb (p=0.02) and increased internal carotid velocity (p=0.05) were the independent variables associated with the ECG strain pattern. ConclusionIdentification of ECG strain pattern is correlated with myocardial ischemia risk, so it could be helpful in risk stratification of children and adolescents with ESRD. Factors determining ECG strain are prolonged disease duration, increased LVM, higher TC, lower Hb and increased internal carotid velocity could become an important part of management of ESRD patients.

PS261 Risk Stratification in Children With Heart Disease:

PS261 Risk Stratification in Children With Heart Disease: