Cardiac Biomarkers in Pediatric Cardiomyopathy: Study Design and Recruitment Results from the Pediatric Cardiomyopathy Registry.

BACKGROUND: Cardiomyopathies are a rare cause of pediatric heart disease, but they are one of the leading causes of heart failure admissions, sudden death, and need for heart transplant in childhood. Reports from the Pediatric Cardiomyopathy Registry (PCMR) have shown that almost 40% of children presenting with symptomatic cardiomyopathy either die or undergo heart transplant within 2 years of presentation. Little is known regarding circulating biomarkers as predictors of outcome in pediatric cardiomyopathy. STUDY DESIGN: The Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers) study is a multi-center prospective study conducted by the PCMR investigators to identify serum biomarkers for predicting outcome in children with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Patients less than 21 years of age with either DCM or HCM were eligible. Those with DCM were enrolled into cohorts based on time from cardiomyopathy diagnosis: categorized as new onset or chronic. Clinical endpoints included sudden death and progressive heart failure. RESULTS: There were 288 children diagnosed at a mean age of 7.2±6.3 years who enrolled in the PCM Biomarkers Study at a median time from diagnosis to enrollment of 1.9 years. There were 80 children enrolled in the new onset DCM cohort, defined as diagnosis at or 12 months prior to enrollment. The median age at diagnosis for the new onset DCM was 1.7 years and median time from diagnosis to enrollment was 0.1 years. There were 141 children enrolled with either chronic DCM or chronic HCM, defined as children ≥2 years from diagnosis to enrollment. Among children with chronic cardiomyopathy, median age at diagnosis was 3.4 years and median time from diagnosis to enrollment was 4.8 years. CONCLUSION: The PCM Biomarkers study is evaluating the predictive value of serum biomarkers to aid in the prognosis and management of children with DCM and HCM. The results will provide valuable information where data are lacking in children. CLINICAL TRIAL REGISTRATION NCT01873976: https://clinicaltrials.gov/ct2/show/NCT01873976?term=PCM+Biomarker&rank=1.

Health-Related Quality of Life and Functional Status Are Associated with Cardiac Status and Clinical Outcome in Children with Cardiomyopathy.

OBJECTIVES: To measure the health-related quality of life (HRQOL) and functional status of children with cardiomyopathy and to determine whether they are correlated with sociodemographics, cardiac status, and clinical outcomes. STUDY DESIGN: Parents of children in the Pediatric Cardiomyopathy Registry completed the Child Health Questionnaire (CHQ; age ≥ 5 years) and Functional Status II (Revised) (age ≤ 18 years) instruments. Linear and Cox regressions were used to examine hypothesized associations with HRQOL. RESULTS: The 355 children evaluated at ≥ 5 years (median 8.6 years) had lower functioning (CHQ Physical and Psychosocial Summary Scores 41.7 ± 14.4 and 47.8 ± 10.7) than that of healthy historical controls. The most extreme CHQ domain score, Parental Impact-Emotional, was one SD below normal. Younger age at diagnosis and smaller left ventricular end-diastolic dimension z score were associated independently with better physical functioning in children with dilated cardiomyopathy. Greater income/education correlated with better psychosocial functioning in children with hypertrophic and mixed/other types of cardiomyopathy. In the age ≥ 5 year cohort, lower scores on both instruments predicted earlier death/transplant and listing for transplant in children with dilated and mixed/other types of cardiomyopathy (P < .001). Across all ages (n = 565), the Functional Status II (Revised) total score was 87.1 ± 16.4, and a lower score was associated with earlier death/transplant for all cardiomyopathies. CONCLUSIONS: HRQOL and functional status in children with cardiomyopathy is on average impaired relative to healthy children. These impairments are associated with older age at diagnosis, lower socioeconomic status, left ventricular size, and increased risk for death and transplant. Identification of families at risk for functional impairment allows for provision of specialized services early in the course of disease. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00005391.

Issues in solid-organ transplantation in children: translational research from bench to bedside.

In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children.

Issues in solid-organ transplantation in children: translational research from bench to bedside

In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children.

Proteinuria in children infected with the human immunodeficiency virus.

OBJECTIVES: To determine the prevalence of proteinuria in a large cohort of children infected with the human immunodeficiency virus (HIV) and their longitudinal progression during treatment with highly active antiretroviral therapy. STUDY DESIGN: In a retrospective cohort study, 286 children infected with HIV were monitored with quantitative assays of proteinuria from January 1998 through January 2007, with monitoring of viral load, lymphocyte profiles, kidney function, and mortality rates. Proteinuria was quantitated by urine protein to creatinine ratio (Upr/cr). RESULTS: Ninety-four (33%) had proteinuria at baseline. Of these, 32 (11.2%) had nephrotic range proteinuria (Upr/cr > or = 1.0). Initial screening was at 11 +/- 0.3 years of age, with an average follow-up of 5.6 +/- 0.1 years. The mortality rate was significantly greater in those with proteinuria. During the period of observation, 15 patients with nephrotic proteinuria died or had development of end-stage renal disease, and 16 showed improvement. Of those with intermediate range proteinuria (Upr/cr > or = 0.2 < 1.0), 3 progressed to nephrotic range proteinuria, and 39 (63%) showed resolution of the proteinuria (Upr/cr < 0.2). Improvement in proteinuria was correlated with decreasing viral load (r = 0.5; P < .01). CONCLUSIONS: Control of viral load with highly active antiretroviral therapy appears to prevent the progression of HIV-associated renal disease and improve survival rates in infected children.

The relationship between nutritional and sociodemographic factors and the likelihood of children in the Dominican Republic having a BCG scar.

OBJECTIVES: To critically assess the prevalence among schoolchildren 6 to 9 years of age throughout the Dominican Republic of a bacille Calmette-Guérin (BCG) vaccination scar, and to examine the relationship between nutritional and sociodemographic factors and the likelihood of having a BCG scar. METHODS: This correlational study used the database of the Second National Census on Height and Weight of Elementary School First Grade Students, which was conducted in the Dominican Republic August 2001-May 2002, to provide a critical assessment of BCG coverage nationwide. The Census information for the children included the presence of BCG scar, their nutritional status, and basic demographic data. We developed a new sociodemographic indicator, the "Rosa Index," to examine the potential influence of poverty and other environmental characteristics on scar presence. We used logistic regression models to predict the presence of a BCG scar. RESULTS: An overall BCG scar prevalence of 55.3% (85,644/154,887) was found. Malnourished children were less likely to have a BCG scar than were children with adequate nutritional status (odds ratio = 0.91; 95% confidence interval: 0.87, 0.95, P < 0.05). Children who were 7-9 years old were less likely to have a BCG scar than were children 6 years old. Children in the areas of the country more than two hours' driving distance from the capital city of Santo Domingo more often exhibited lower BCG scar prevalence levels than did children in Santo Domingo. A higher Rosa Index (better level of socioeconomic characteristics) was correlated with higher BCG scar prevalence values (r = 0.54, P < 0.05). CONCLUSIONS: Our study findings indicate that BCG coverage appears to be inadequate for schoolchildren in the Dominican Republic. Nevertheless, the presence of a scar in a higher proportion of younger children suggests that coverage has improved in recent years. More programmatic and economic emphasis needs to be placed on extending early BCG vaccination coverage to the areas of the country where vaccination coverage is lower, and on examining the potential role that poverty may have on vaccination effectiveness.

The relationship between nutritional and sociodemographic factors and the likelihood of children in the Dominican Republic having a BCG scar

OBJECTIVE: To critically assess the prevalence among schoolchildren 6 to 9 years of age throughout the Dominican Republic of a bacille Calmette-Guerin (BCG) vaccination scar, and to examine the relationship between nutritional and sociodemographic factors and the likelihood of having a BCG scar. METHODS: This correlational study used the database of the Second National Census on Height and Weight of Elementary School First Grade Students, which was conducted in the Dominican Republic August 2001-May 2002, to provide a critical assessment of BCG coverage nationwide. The Census information for the children included the presence of BCG scar, their nutritional status, and basic demographic data. We developed a new sociodemographic indicator, the "Rosa Index", to examine the potential influence of poverty and other environmental characteristics on scar presence. We used logistic regression models to predict the presence of a BCG scar. RESULTS: An overall BCG scar prevalence of 55.3 percent (85 644/154 887)was found. Malnourished children were less likely to have a BCG scar than were children with adequate nutritional status (odds ratio = 0.91; 95 percent confidence interval: 0.87, 0.95, P<0.05). Children who were 7-9 years old were less likely to have a BCG scar than were children 6 years old. Children in the areas of the country more than two hours' driving distance from the capital city of Santo Domingo more often exhibited lower BCG scar prevalence levels than did children in Santo Domingo. A higher Rosa Index (better level of socioeconomic characteristics) was correlated with higher BCG scar prevalence values (r=0.54, P<0.05). CONCLUSIONS: Our study findings indicate that BCG coverage appears to be inadequate for schoolchildren in the Dominican Republic. Nevertheless, the presence of a scar in a higher proportion of younger children suggests that coverage has improved in recent years. More programmatic and economic emphasis needs to be placed on extending early BCG vaccination coverage to the areas of the country where vaccination coverage is lower, and on examining the potential role that poverty may have on vaccination effectiveness (AU)

The relationship between nutritional and sociodemographic factors and the likelihood of children in the Dominican Republic having a BCG scar / Relación entre los factores nutricionales y sociodemográficos y la probabilidad de que los niños de la República Dominicana tengan cicatriz de BCG

OBJECTIVES: To critically assess the prevalence among schoolchildren 6 to 9 years of age throughout the Dominican Republic of a bacille Calmette-Guérin (BCG) vaccination scar, and to examine the relationship between nutritional and sociodemographic factors and the likelihood of having a BCG scar. METHODS: This correlational study used the database of the Second National Census on Height and Weight of Elementary School First Grade Students, which was conducted in the Dominican Republic August 2001-May 2002, to provide a critical assessment of BCG coverage nationwide. The Census information for the children included the presence of BCG scar, their nutritional status, and basic demographic data. We developed a new sociodemographic indicator, the "Rosa Index," to examine the potential influence of poverty and other environmental characteristics on scar presence. We used logistic regression models to predict the presence of a BCG scar. RESULTS: An overall BCG scar prevalence of 55.3 percent (85 644/154 887) was found. Malnourished children were less likely to have a BCG scar than were children with adequate nutritional status (odds ratio = 0.91; 95 percent confidence interval: 0.87, 0.95, P < 0.05). Children who were 7-9 years old were less likely to have a BCG scar than were children 6 years old. Children in the areas of the country more than two hours' driving distance from the capital city of Santo Domingo more often exhibited lower BCG scar prevalence levels than did children in Santo Domingo. A higher Rosa Index (better level of socioeconomic characteristics) was correlated with higher BCG scar prevalence values (r = 0.54, P < 0.05). CONCLUSIONS: Our study findings indicate that BCG coverage appears to be inadequate for schoolchildren in the Dominican Republic. Nevertheless, the presence of a scar in a higher proportion of younger children suggests that coverage has improved in recent years. More programmatic and economic emphasis needs...

OBJETIVOS: Evaluar críticamente la prevalencia de cicatrices por la vacunación con el bacilo de Calmette-Guérin (BCG) en niños de 6 a 9 años de la República Dominicana y examinar la relación entre los factores nutricionales y socioeconómicos y la probabilidad de tener cicatriz de BCG. MÉTODOS: Para este estudio correlacional se empleó la base de datos del II Censo Nacional de Talla y Peso en Escolares de Primer Grado de Básica, realizado en la República Dominicana entre agosto de 2001 y mayo de 2002, para evaluar críticamente el nivel de cobertura nacional de la vacunación con BCG. Entre la información censal de los niños estaban si tenían cicatriz de BCG, su estado nutricional y sus datos demográficos básicos. Se desarrolló un nuevo indicador sociodemográfico, el "índice de Rosa", para analizar la posible influencia de la pobreza y de otras características ambientales en la presencia de esa cicatriz. Se emplearon modelos de regresión logística para predecir la presencia de la cicatriz de BCG. RESULTADOS: La prevalencia general de cicatrices de BCG fue de 55,3 por ciento (85 644/ 154 887). Los niños desnutridos presentaron una menor probabilidad de tener cicatriz de BCG que los niños con un adecuado estado nutricional (razón de posibilidades = 0,91; intervalo de confianza de 95 por ciento: 0,87 a 0,95; P < 0,05). Los niños de 7-9 años tuvieron menor probabilidad de tener cicatriz de BCG que los niños de 6 años. Los niños de zonas del país que se encuentran a más de dos horas de viaje de Santo Domingo, la capital, presentaron menor prevalencia de cicatrices de BCG con mayor frecuencia que los niños de Santo Domingo. Se encontró correlación entre tener un mayor índice de Rosa (mejor nivel en las características socioeconómicas) y una mayor prevalencia de cicatrices de BCG (r = 0,54; P < 0,05). CONCLUSIONES: Los resultados del presente estudio indican que la cobertura de vacunación de escolares con la vacuna BCG parece no ser la adecuada...

Cancer incidence among Hispanic children in the United States

OBJETIVO: Comparar de manera directa la incidencia de cáncer en niños hispanos y en niños blancos no hispanos en los estados de California y la Florida, donde viven casi las dos terceras partes de toda la población infantil hispana de Estados Unidos de América. MÉTODOS: Del Sistema de Estadísticas de Cáncer de la Florida (Florida Cancer Data System) y del Registro de Cáncer de California (California Cancer Registry) se sacaron datos transversales de 1988 a 1998 correspondientes a todos los casos nuevos de cáncer en niños (<15 años de edad), codificados según raza u origen étnico en "hispanos" o "blancos no hispanos". Los resultados se expresaron en forma de tasas de incidencia estandarizadas por edad, usando como referencia la población mundial estándar en millones de habitantes. Se comparó la frecuencia de cáncer en niños hispanos y en niños blancos no hispanos mediante razones de incidencia estandarizadas (RIE) y sus respectivos intervalos de confianza del 95% (IC95%). RESULTADOS: Al compararse la frecuencia de todos los tipos de cáncer en niños hispanos y niños blancos no hispanos, la RIE fue de 1,02 (IC95%: 0,99 a 1,05). Al examinarse ciertos tipos de tumores en particular, las RIE apuntaron a mayores tasas de incidencia de leucemia (RIE = 1,26; IC95%: 1,19 a 1,34), linfoma de Hodgkin (RIE = 1,29; IC95%: 1,08 a 1,54), y tumores de células germinativas (RIE = 1,62; IC95%: 1,34 a 1,96) en niños hispanos. Estos últimos tuvieron menores incidencias de tumores del sistema nervioso central (RIE = 0,72; IC95%: 0,66 a 0,78) y de tumores del sistema nervioso simpático (RIE = 0,76; IC95%: 0,66 a 0,87). En lo que respecta a diferencias entre estados, la incidencia de linfoma, de tumores del sistema nervioso central, de tumores del sistema nervioso simpático y de tumores óseos malignos fue mayor entre jóvenes hispanos residentes de la Florida; en cambio, la incidencia de hepatomas malignos fue mayor entre jóvenes hispanos residentes de California. CONCLUSIONES: Aunque la incidencia general de cáncer en niños hispanos fue semejante a la observada en niños blancos no hispanos, se hallaron diferencias significativas en el caso de ciertos tumores en particular. Habida cuenta de que ser hispano puede ser un factor de confusión en relación con otros factores de riesgo de cáncer (familiares, socioeconómicos o ambientales), se recomienda explorar estos últimos factores en futuras investigaciones sobre el riesgo de cáncer en niños hispanos.