Associations Between Postoperative Management in the Critical Care Unit and Adolescent Developmental Outcomes Following Cardiac Surgery in Infancy: An Exploratory Study.

OBJECTIVES: Children with congenital heart disease are at high risk for developmental sequelae. Most studies focus on preoperative and intraoperative predictors of developmental impairment, with less attention to the postoperative period. The relationship between patient-related factors specific to the postoperative course in the PICU following cardiac surgery with long-term neurodevelopmental outcomes in adolescence was examined. DESIGN: Retrospective chart review of patients previously recruited to a study describing their developmental outcomes in adolescence. SETTING: Single tertiary care pediatric hospital in Canada. PATIENTS: Eighty adolescents, born between 1991 and 1999, with congenital heart disease who required open-heart surgery before 2 years old. MEASUREMENTS AND MAIN RESULTS: Several variables related to acuity of illness and complexity of postoperative course in the PICU were collected. Outcome measures included the Movement-Assessment Battery for Children-2 (motor), Leiter Brief Intelligence Quotient (cognition), and Strength and Difficulties Questionnaire (behavior). Analyses examined associations between PICU variables and long-term outcomes. Longer mechanical ventilation (ß = -0.49; p = 0.013) and dopamine use (ß = -14.41; p = 0.012) were associated with lower motor scores. Dopamine use was associated with lower cognitive scores (ß = -14.02; p = 0.027). Longer PICU stay (ß = 0.18; p = 0.002), having an open chest postoperatively (ß = 3.83; p = 0.017), longer mechanical ventilation (ß = 0.20; p = 0.001), longer inotrope support (ß = 0.27; p = 0.002), hours on dopamine (ß = 0.01; p = 0.007), days to enteral feeding (ß = 0.22; p = 0.012), lower hemoglobin (ß = -0.11; p = 0.004), and higher creatinine (ß = 0.05; p = 0.014) were all associated with behavioral difficulties. CONCLUSIONS: Several important developmental outcomes in adolescents were associated with factors related to their postoperative course in the PICU as infants. Findings may highlight those children at highest risk for neurodevelopmental sequelae and suggest new approaches to critical care management following open-heart surgery, with the aim of mitigating or preventing adverse long-term outcomes.

Participation in leisure activities in adolescents with congenital heart defects.

AIM: To describe leisure participation in adolescents with congenital heart defects (CHD) and identify factors associated with intensity of participation. METHOD: Eighty adolescents with CHD were recruited (39 males, 41 females; mean age [SD] 15y 8mo [1y 8mo] range 11y 5mo-19y 11mo) of whom 78 completed the Children's Assessment of Participation and Enjoyment (CAPE) outcome measure of leisure participation. The measure has five subscales: recreational, active-physical, social, skill-based, and self-improvement. Associations between the CAPE and age, sex, and development were examined. Motor ability (Movement Assessment Battery for Children, Second Edition), cognition (Leiter International Performance Scale-Revised), behavior (Strengths and Difficulties Questionnaire), and motivation (Dimensions of Mastery Questionnaire) were assessed. RESULTS: Participants exhibited impaired motor (43.5%), behavioral (23.7%), and cognitive (29.9%) development. The most intense participation was in social (mean [SD] 3.3 [0.99]) and recreational (2.9 [0.80]) activity types on the CAPE. Male sex (p<0.05) and younger age were associated with greater physical activity (<15y: 1.87; ≥15y: 1.31, p<0.05). Greater engagement in social activities was related to better cognition (r=0.28, p<0.05), higher motor function (r=0.30-0.36, p<0.01), and fewer behavioral difficulties (r=-0.32 to -0.47, p<0.01). Cognitive ability (r=0.27, p<0.05), dexterity and aiming/catching (r=0.27-0.33, p<0.05), and behavior problems (r=0.38-0.49, p=0.001) were correlated with physical activity participation. Persistence in tasks, an aspect of motivation, correlated with physical (r=0.45, p<0.001) and social activity involvement (r=0.28, p<0.05). INTERPRETATION: Ongoing developmental impairments in adolescents with CHD are associated with decreased active-physical and social engagement, putting them at risk of poor physical and mental health. Health promotion strategies should be considered. WHAT THIS PAPER ADDS: Adolescents with congenital heart defects (CHD) have limited engagement in active-physical leisure activities. Cognitive, motor, and behavioral impairments are associated with decreased participation in leisure in children with CHD. Female sex and older age are associated with less engagement in leisure. Mastery motivation correlates with participation, suggesting an avenue for intervention.

Participación en actividades recreativas en adolescentes con cardiopatías congénitas OBJETIVO: Describir la participación en el tiempo libre en adolescentes con defectos cardíacos congénitos (CHD) e identificar los factores asociados con la intensidad de la participación. MÉTODO: Ochenta adolescentes con CHD fueron reclutados (39 varones, 41 mujeres; edad media [DE] 15 años 8 meses [1 año 8 meses] rango 11 año 5 meses- 19 año 11 meses) de los cuales 78 completaron la medida de resultado de la Evaluación de la Participación y el Disfrute de los Niños (Children's Assessment of Participation and Enjoyment [CAPE]) del ocio participación. La medida tiene cinco subescalas: recreación, actividad física, social, basada en habilidades y mejoría personal. Se examinaron las asociaciones entre el CAPE y la edad, el sexo y el desarrollo. Se evaluó la capacidad motora con la Batería de Evaluación de Movimiento para Niños (Movement Assessment Battery for Children, Segunda edición), la cognición (Leiter International Performance Scale-Revised), el comportamiento con el Cuestionario de Fortalezas y Dificultades (Strengths and Difficulties Questionnaire) y la motivación usando el cuestionario Dimensiones del Dominio (Dimensions of Mastery Questionnaire). RESULTADOS: Los participantes exhibieron problemas en el desarrollo motor (43.5%), conducta (23.7%) y en el desarrollo cognitivo (29.9%). La participación más intensa fue en los tipos de actividad social (media [DE] 3.3 [0.99]) y recreativa (2.9 [0.80]) en el CAPE. El sexo masculino (p <0.05) y la edad más joven se asociaron con una mayor actividad física (<15 años: 1.87; ≥15 años: 1.31, p <0.05). Una mayor participación en actividades sociales se relacionó con una mejor cognición (r = 0.28, p <0.05), una función motora más alta (r = 0.30-0.36, p <0.01) y menos dificultades en el comportamiento (r = -0.32 a -0.47, p < 0,01). La capacidad cognitiva (r = 0.27, p <0.05), la destreza manual y la habilidad para apuntar y atajar (r = 0.27-0.33, p <0.05) y los problemas de comportamiento (r = 0.38-0.49, p = 0.001) se correlacionaron con la participación en la actividad física. La capacidad de persistir en las tareas, un aspecto de la motivación se correlacionó con la participación física (r = 0.45, p <0.001) y la actividad social (r = 0.28, p <0.05). INTERPRETACIÓN: Los problemas de desarrollo en los adolescentes con CHD están asociados con una disminución de la participación física y social, lo que los pone a riesgo de una pobre salud física y mental. Deben buscarse estrategias para la promoción de la salud de esta población.

Participação em atividades de lazer em adolescentes com defeitos cardíacos congênitos OBJETIVO: Descrever a participação em lazer de adolescentes com defeitos cardíacos congênitos (DCC) e identificar fatores associados com a intensidade de participação. MÉTODO: Oitenta adolescentes com DCC foram recrutados (39 do sexo masculino, 41 do sexo feminino; média de idade [DP] 15a 8m [1a 8m] variação 11a 5m-19a 11m), dos quais 78 completaram a medida de participação em lazer Avaliação da participação e diversão das crianças (APDC). A medida tem cinco subescalas: recreacional, ativa-física, social, baseada em habilidades, e auto-aprimoramento. Associações entre a APDC e idade, sexo e desenvolvimento foram examinadas. A capacidade motora (Bateria de avaliação do movimento para crianças, segunda edição), cognição (Escala internacional de desempenho de Leiter- Revisada), comportamento (Questionário de capacidades e dificuldades), e motivação (Questionário de Dimensões do Domínio) foram avaliados. RESULTADOS: Os participantes exibiram comprometimento do desenvolvimento motor (43,5%), comportamental (23,7%), e cognitivo (29,9%). A participação mais intensa segundo a APDC foi nos tipos social (média [DP] 3,3 [0,99]) e recreacional (2.9 [0,80]). O sexo masculino (p<0,05) e menor idade foram associados com maior nível de atividade física (<15a: 1,87; ≥15a: 1,31, p<0,05). Um maior engajamento em atividades sociais foi relacionado com uma melhor cognição (r=0,28, p<0,05), maior função motora (r=0,30-0,36, p<0,01), e menos dificuldades comportamentais (r=-0,32 a -0,47, p<0,01). A capacidade cognitiva (r=0,27, p<0,05), destreza e mirar/apreender (r=0,27-0,33, p<0,05), e problemas comportamentais (r=0,38-0,49, p=0,001) foram correlacionadas com a participação em atividades físicas. A persistência nas tarefas, um aspecto da motivação, se correlacionou com o envolvimento em atividades físicas (r=0,45, p<0,001) e sociais (r=0,28, p<0,05). INTERPRETAÇÃO: Alterações persistentes do desenvolvimento de adolescentes com DCC são associadas com engajamento ativo-físico e social reduzidos, o que os coloca em risco para sua saúde física e mental. Estratégias de promoção de saúde deveriam ser consideradas.

A Comparison of Developmental Outcomes of Adolescent Neonatal Intensive Care Unit Survivors Born with a Congenital Heart Defect or Born Preterm.

OBJECTIVE: To compare cognitive, motor, behavioral, and functional outcomes of adolescents born with a congenital heart defect (CHD) and adolescents born preterm. STUDY DESIGN: Adolescents (11-19 years old) born with a CHD requiring open-heart surgery during infancy (n = 80) or born preterm ≤29 weeks of gestational age (n = 128) between 1991 and 1999 underwent a cross-sectional evaluation of cognitive (Leiter International Performance Scale-Revised), motor (Movement Assessment Battery for Children-II), behavioral (Strengths and Difficulties Questionnaire), and functional (Vineland Adaptive Behavior Scale-II) outcomes. Independent samples t tests and Pearson χ2 or Fisher exact tests were used to compare mean scores and proportions of impairment, respectively, between groups. RESULTS: Adolescents born with a CHD and adolescents born preterm had similar cognitive, motor, behavioral, and functional outcomes. Cognitive deficits were detected in 14.3% of adolescents born with a CHD and 11.8% of adolescents born preterm. Motor difficulties were detected in 43.5% of adolescents born with a CHD and 50% of adolescents born preterm. Behavioral problems were found in 23.7% of adolescents in the CHD group and 22.9% in the preterm group. Functional limitations were detected in 12% of adolescents born with a CHD and 7.3% of adolescents born preterm. CONCLUSIONS: Adolescents born with a CHD or born preterm have similar profiles of developmental deficits. These findings highlight the importance of providing long-term surveillance to both populations and guide the provision of appropriate educational and rehabilitation services to better ameliorate long-term developmental difficulties.

Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation.

BACKGROUND: Delayed graft function (DGF) and slow graft function (SGF) are ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long-term graft survival after kidney transplantation. Regulatory T (Treg) cells are protective in murine AKI, and their suppressive function predictive of AKI in kidney transplantation. The conventional Treg cell function coculture assay is however time-consuming and labor intensive. We sought a simpler alternative to measure Treg cell function and predict AKI. METHODS: In this prospective observational cohort study, pretransplant recipient circulating CD4+CD25+CD127lo/- and CD4+CD127lo/- tumor necrosis factor receptor 2 (TNFR2)+ Treg cells were measured by flow cytometry in 76 deceased donor kidney transplant recipients (DGF, n = 18; SGF, n = 34; immediate graft function [IGF], n = 24). In a subset of 37 recipients, pretransplant circulating Treg cell-suppressive function was also quantified by measuring the suppression of autologous effector T-cell proliferation by Treg cell in coculture. RESULTS: The TNFR2+ expression on CD4+CD127lo/- T cells correlated with Treg cell-suppressive function (r = 0.63, P < 0.01). In receiver operating characteristic curves, percentage and absolute number of CD4+CD127lo/-TNFR2+ Treg cell predicted DGF from non-DGF (IGF + SGF) with area under the curves of 0.75 and 0.77, respectively, and also AKI (DGF + SGF) from IGF with area under the curves of 0.76 and 0.72, respectively (P < 0.01). Prediction of AKI (DGF + SGF) from IGF remained significant in multivariate logistic regression accounting for cold ischemic time, donor age, previous transplant, and pretransplant dialysis modality. CONCLUSIONS: Pretransplant recipient circulating CD4+CD127lo/-TNFR2+ Treg cell is potentially a simpler alternative to Treg cell function as a pretransplant recipient immune marker for AKI (DGF + SGF), independent from donor and organ procurement characteristics.

Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

BACKGROUND: Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation. METHODS: Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16) groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was quantified by flow cytometry. Regulatory T-cell suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture. RESULTS: Pretransplantation Treg suppressive function, but not frequency, was decreased in AKI recipients (P<0.01). In univariate and multivariate analyses accounting for the effects of cold ischemic time and donor age, Treg suppressive function discriminated DGF from immediate graft function recipients in multinomial logistic regression (odds ratio, 0.77; P<0.01), accurately predicted AKI in receiver operating characteristic curve (area under the curve, 0.82; P<0.01), and predicted 14-day estimated glomerular filtration rate in linear regression (P<0.01). CONCLUSION: Our results indicate that recipient peripheral blood Treg suppressive function is a potential independent pretransplantation predictor of DGF and SGF.

The use of angiogenic-antimicrobial agents in experimental wounds in animals: problems and solutions.

A topical combination (silvathymosin) of natural proangiogeneic protein thymosin ß4 (Tß4) and antimicrobial silver sulfadiazine was hypothesized to promote the healing of large, full-thickness, clean or infected wounds in rats. Silvathymosin showed the fastest wound healing (85%) followed by silver sulfadiazine (84%) and Tß4 (72%). In the infected groups, the healing pattern was different, as Tß4 and silvathymosin groups did not show similar wound healing. Wound histopathology and VEGF and KI67 immunohistochemical assessment of angiogenesis was consistent and correlated well with the tempo of healing of the acute wounds. These preliminary data demonstrate the more rapid acute wound healing properties of the combination formulation of thymosin ß4 and silver sulfadiazine as compared to these agents alone. This novel agent could prove an effective treatment modality for debilitating chronic wounds and decubitus ulcers.