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.

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.