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OBJECTIVES: To make practical and evidence-based recommendations on improving understanding of bleeding and thrombosis with pediatric extracorporeal life support and to make recommendations for research directions. DATA SOURCES: Evaluation of literature and consensus conferences of pediatric critical care and extracorporeal life support experts. STUDY SELECTION: A team of 10 experts with pediatric cardiac and extracorporeal membrane oxygenation experience and expertise met through the Pediatric Cardiac Intensive Care Society to review current knowledge and make recommendations for future research to establish "best practice" for anticoagulation management related to extracorporeal life support. DATA EXTRACTION/SYNTHESIS: The first of a two-part white article focuses on clinical understanding and limitations of medications in use for anticoagulation, including novel medications. For each medication, limitations of current knowledge are addressed and research recommendations are suggested to allow for more definitive clinical guidelines in the future. CONCLUSIONS: No consensus on best practice for anticoagulation exists. Structured scientific evaluation to answer questions regarding anticoagulant medication and bleeding and thrombotic events should occur in multicenter studies using standardized approaches and well-defined endpoints. Outcomes related to need for component change, blood product administration, healthcare outcome, and economic assessment should be incorporated into studies. All centers should report data on patients receiving extracorporeal life support to a registry. The Extracorporeal Life Support Organization registry, designed primarily for quality improvement purposes, remains the primary and most successful data repository to date.
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Oxigenação por Membrana Extracorpórea/efeitos adversos , Hemorragia/prevenção & controle , Trombose/prevenção & controle , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacologia , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Antitrombinas/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Criança , Estado Terminal/terapia , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/tendências , Humanos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacologiaRESUMO
OBJECTIVES: To make recommendations on improving understanding of bleeding and thrombosis with pediatric extracorporeal life support including future research directions. DATA SOURCES: Evaluation of literature and consensus conferences of pediatric critical care and extracorporeal life support experts. STUDY SELECTION: A team of 10 experts with pediatric cardiac and extracorporeal membrane oxygenation experience and expertise met through the Pediatric Cardiac Intensive Care Society to review current knowledge and make recommendations for future research to establish "best practice" for anticoagulation management related to extracorporeal life support. DATA EXTRACTION/DATA SYNTHESIS: This white paper focuses on clinical understanding and limitations of current strategies to monitor anticoagulation. For each test of anticoagulation, limitations of current knowledge are addressed and future research directions suggested. CONCLUSIONS: No consensus on best practice for anticoagulation monitoring exists. Structured scientific evaluation to answer questions regarding anticoagulation monitoring and bleeding and thrombotic events should occur in multicenter studies using standardized approaches and well-defined endpoints. Outcomes related to need for component change, blood product administration, healthcare outcome, and economic assessment should be incorporated into studies. All centers should report data on patient receiving extracorporeal life support to a registry.
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Oxigenação por Membrana Extracorpórea/efeitos adversos , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Criança , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/tendências , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacologia , Hemorragia/prevenção & controle , Humanos , Trombose/prevenção & controle , Fator de von Willebrand/administração & dosagem , Fator de von Willebrand/efeitos adversos , Fator de von Willebrand/farmacologiaRESUMO
BACKGROUND: Given the central role of the thalamus in motor, sensory, and cognitive development, methods to study emerging thalamocortical connectivity in early infancy are of great interest. PURPOSE: To determine the feasibility of performing probabilistic tractography-based thalamic parcellation (PTbTP) in typically developing (TD) neonates and to compare the results with a pilot sample of neonates with congenital heart disease (CHD). STUDY TYPE: Institutional Review Board (IRB)-approved cross-sectional study. MODEL: We prospectively recruited 20 TD neonates and five CHD neonates (imaged preoperatively). FIELD STRENGTH/SEQUENCE: MRI was performed at 3.0T including diffusion-weighted imaging (DWI) and 3D magnetization prepared rapid gradient-echo (MPRAGE). ASSESSMENT: A radiologist and trained research assistants segmented the thalamus and seven cortical targets for each hemisphere. Using the thalami as seeds and the cortical labels as targets, FSL library tools were used to generate probabilistic tracts. A Hierarchical Dirichlet Process algorithm was then used for clustering analysis. A radiologist qualitatively assessed the results of clustering. Quantitative analyses were also performed. STATISTICAL TESTS: We summarized the demographic data and results of clustering with descriptive statistics. Linear regressions covarying for gestational age were used to compare groups. RESULTS: In 17 of 20 TD neonates, we identified five connectivity-determined clusters, which correlate with known thalamic nuclei and subnuclei. In four neonates with CHD we observed a spectrum of abnormalities including fewer and disorganized clusters or small supernumerary clusters (up to seven per thalamus). After covarying for differences in corrected gestational age (cGA), the fractional anisotropy (FA), volume, and normalized thalamic volume were significantly lower in CHD neonates (P < 0.01). DATA CONCLUSIONS: Using PTbTP clusters, correlating well with the location and connectivity of known thalamic nuclei, were identified in TD neonates. Differences in thalamic clustering outputs were identified in four neonates with CHD, raising concern for disordered thalamic connectivity. PTbTP is feasible in TD and CHD neonates. Preliminary findings suggest the prenatal origins of altered connectivity in CHD. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1626-1637.
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Cardiopatias Congênitas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tálamo/diagnóstico por imagem , Algoritmos , Anisotropia , Estudos Transversais , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Recém-Nascido , Masculino , Fenótipo , Probabilidade , Estudos Prospectivos , Controle de Qualidade , Tamanho da AmostraRESUMO
OBJECTIVE: To describe strokes in patients with acquired or congenital heart disease and investigate risk factors for in-hospital mortality and ongoing neurologic deficits. DESIGN: Single-center, retrospective review of cardiac, neurologic, and radiologic patient databases. SETTING: Tertiary care children's hospital. PATIENTS: All patients with acquired or congenital heart disease admitted from January 2010 to October 2014 identified with stroke. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-four stroke events were identified in 83 patients (median age, 5.9 mo; interquartile range, 0.8-33.4). Thirty-two patients (38%) had single ventricle congenital heart disease. Eight patients (9%) presented with symptoms at home, and the remainder was diagnosed while already admitted to the hospital. Forty patients (48%) presented with clinically evident neurologic deficits (e.g., weakness, seizures). Fifty-eight patients (69%) had arterial ischemic strokes, and 13 (15%) had parenchymal hemorrhages. At diagnosis, 54 patients (64%) were on inotropes. Twenty-nine patients (35%) had greater than or equal to 3 cardiac procedures during their hospitalization before stroke diagnosis. In-hospital mortality occurred in 28 patients (33%). Under multivariate analysis, inotropes, number of cardiac procedures, lack of seizure, and parenchymal hemorrhage were independently associated with in-hospital mortality (p < 0.05). Fifty-four percent of survivors with neurologic follow-up had ongoing neurologic deficits attributable to strokes (median follow-up, 15.3 mo; interquartile range, 7.0-29.9). With multivariate analysis, longer hospital stay (p = 0.02) was independently associated with ongoing deficits. CONCLUSIONS: A majority of patients with acquired or congenital heart disease who suffer stroke present while hospitalized and without focal neurologic findings. In-hospital mortality is associated with inotropes, cardiac procedures, lack of seizure, and parenchymal hemorrhage. The majority of survivors have lasting neurologic deficits associated with longer hospital stay.
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Cardiopatias/complicações , Mortalidade Hospitalar , Acidente Vascular Cerebral/etiologia , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Seguimentos , Cardiopatias Congênitas/complicações , Cardiopatias/diagnóstico , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologiaRESUMO
We report the first observation of room-temperature quantum-confined photoluminescence (PL) from low-dimensional Ge(1-x)Sn(x)/Ge superlattices (SLs) up to a high Sn content of 6.96%. Both direct and indirect emissions associated with the interband transitions between minibands in the conduction bands and valence band were observed at room temperature. As the Sn content is increased, the energy difference between the lowest direct and indirect transitions is reduced, indicating an effective modification of the band structure desired for optoelectronics. The integrated PL intensity ratio of direct to indirect recombinations is significantly enhanced with increasing Sn content due to the reduced Γ-L energy separation and quantum confinement effect. Those results suggest that Sn-based low-dimensional structures are promising material for efficient Si-based lasers.
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We sought to describe contemporary outcomes and identify risk factors for hospital mortality in premature neonates with critical congenital heart disease who were referred for early intervention. Neonates who were born before 37 weeks' gestation with critical congenital heart disease and admitted to our institution from 2002 to 2008 were included in this retrospective cohort study. Critical congenital heart disease was defined as a defect requiring surgical or transcatheter cardiac intervention or a defect resulting in death within the first 28 days of life. Logistic regression analyses were performed to identify risk factors for mortality before hospital discharge. The study included 180 premature neonates, of whom 37 (21%) died during their initial hospitalization, including 6 (4%) before cardiac intervention and 31 (17%) after cardiac intervention. For the 174 patients undergoing cardiac intervention, independent risk factors for mortality were a 5 min Apgar score ≤ 7, need for preintervention mechanical ventilation, and Risk Adjustment in Congenital Heart Surgery category ≥ 4 or not assignable. Mortality for premature infants with critical congenital heart disease who are referred for early intervention remains high. Patients with lower Apgar scores who receive preintervention mechanical ventilation and undergo more complex procedures are at greatest risk.
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Cardiopatias Congênitas/mortalidade , Doenças do Prematuro/mortalidade , Índice de Apgar , Estado Terminal , Feminino , Idade Gestacional , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/terapia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/cirurgia , Doenças do Prematuro/terapia , Masculino , Análise Multivariada , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To use novel optical techniques to measure perioperative cerebral hemodynamics of diverse congenital heart disease (CHD) groups (two-ventricle, d-transposition of the great arteries [TGA], and single ventricle [SV]) and (1) compare CHD groups with healthy controls preoperatively and (2) compare preoperative and postoperative values within each CHD group. METHODS: Frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy were used to measure cerebral oxygen saturation, cerebral blood volume, cerebral blood flow index, cerebral oxygen extraction fraction (OEF, calculated using arterial oxygen saturation and cerebral oxygen saturation), and an index of cerebral metabolic rate of oxygen consumption in control and CHD neonates. Preoperative CHD measures were compared with controls. Preoperative and postoperative measures were compared within each CHD group. RESULTS: In total, 31 CHD neonates (7 two-ventricle, 11 TGA, 13 SV) and 13 controls were included. Only neonates with SV CHD displayed significantly lower preoperative cerebral blood flow index (P < .04) than controls. TGA and SV groups displayed greater OEF (P < .05) during the preoperative period compared with controls. Compared with the preoperative state, postoperative neonates with TGA had a greater arterial oxygen saturation with lower OEF. CONCLUSIONS: Differences in cerebral hemodynamics and oxygen metabolism were observed in diverse CHD groups compared with controls. Increased OEF appears to be a compensatory mechanism in neonates with TGA and SV. Studies are needed to understand the relationship of these metrics to outcome and their potential to guide interventions to improve outcome.
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Circulação Cerebrovascular/fisiologia , Cardiopatias Congênitas/fisiopatologia , Hemodinâmica/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Recém-Nascido , Masculino , Oxigênio/sangue , Assistência Perioperatória , Estudos ProspectivosRESUMO
A key component of musical proficiency is the ability to discriminate between and identify musical intervals, or fixed ratios between pitches. Acquiring these skills requires training, but little is known about how to best arrange the trials within a training session. To address this issue, learning on a musical-interval comparison task was evaluated for two four-day training regimens that employed equal numbers of stimulus presentations per day. A regimen of continuous practice yielded no learning, but a regimen that combined practice and stimulus exposure alone generated clear improvement. Learning in the practice-plus-exposure regimen was due to the combination of the two experiences, because two control groups who received only either the practice or the exposure from that regimen did not learn. Posttest performance suggested that this improvement in comparison learning generalized to an untrained stimulus type and an untrained musical-interval identification task. Naïve comparison performance, but not learning, was better for larger pitch-ratio differences and for individuals with more musical experience. The reported benefits of the practice-plus-exposure regimen mirror the outcomes for fine-grained discrimination and speech tasks, suggesting that a general learning principle is involved. In practical terms, it appears that combining practice and stimulus exposure alone is a particularly effective configuration for improving musical-interval perception.
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Estimulação Acústica/métodos , Estimulação Acústica/psicologia , Aprendizagem/fisiologia , Música/psicologia , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Distribuição Aleatória , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: While therapeutic hypothermia (TH) is an effective neuroprotective therapy for neonatal hypoxic-ischemic encephalopathy, TH has not been demonstrated to improve outcome in other pediatric populations. Patients with acquired or congenital heart disease (CHD) are at high risk of both cardiac arrest and neurodevelopmental impairments, and therapies are needed to improve neurologic outcome. The primary goal of our study was to compare safety/efficacy outcomes in post-arrest CHD patients treated with TH versus controls not treated with TH. METHODS: Patients with CHD treated during the first 18 months after initiation of a post-arrest TH protocol (temperature goal: 33.5⯰C) were compared to historical and contemporary post-arrest controls not treated with TH. Post-arrest data, including temperature, safety measures (e.g. arrhythmia, bleeding), neurodiagnostic data (EEG, neuroimaging), and survival were compared. RESULTS: Thirty arrest episodes treated with TH and 51 control arrest episodes were included. The groups did not differ in age, duration of arrest, post-arrest lactate, or use of ECMO-CPR. The TH group's post-arrest temperature was significantly lower than control's (33.6⯱â¯0.2⯰C vs 34.7⯱â¯0.5⯰C, pâ¯<â¯0.001). There was no difference between the groups in safety/efficacy measures, including arrhythmia, infections, chest-tube output, or neuroimaging abnormalities, nor in hospital survival (TH 61.5% vs control 59.1%, pâ¯=â¯NS). Significantly more controls had seizures than TH patients (26.1% vs. 4.0%, pâ¯=â¯0.04). Almost all seizures were subclinical and occurred more than 24â¯h post-arrest. CONCLUSION: Our data show that pediatric CHD patients who suffer cardiac arrest can be treated effectively and safely with TH, which may decrease the incidence of seizures.
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Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Cardiopatias Congênitas/complicações , Hipotermia Induzida/métodos , Reanimação Cardiopulmonar , Eletroencefalografia , Feminino , Idade Gestacional , Humanos , Hipotermia Induzida/efeitos adversos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Convulsões/etiologia , Fatores de TempoRESUMO
The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.
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Ponte Cardiopulmonar , Circulação Cerebrovascular , Hipotermia Induzida , Oxigênio/metabolismo , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
OBJECTIVE: Critically ill children with congenital heart disease (CHD) are at risk for metabolic bone disease (MBD) and bone fractures. Our objective was to characterize a cohort of CHD patients with fractures and describe a Fragile Bone Protocol (FBP) developed to reduce fractures. DESIGN/SETTING: Patients who developed fractures in the Cardiac Intensive Care Unit (CICU) of Boston Children's Hospital from 3/2008 to 6/2014 were identified via quality improvement and radiology databases. The FBP (initiated July 2011) systematically identifies patients at risk for MBD and prescribes special handling precautions. RESULTS: Twenty-three fractures were identified in 15 children. Median age at fracture identification was 6.2 months, with a median duration of hospitalization before fracture diagnosis of 2.7 months. Six patients (40%) had single ventricle CHD. Hyperparathyroidism and low 25-OH vitamin D levels were present in 77% and 40% of those tested, respectively. Compared with patients not diagnosed with fractures, fracture patients had increased exposure to possible risk factors for MBD and had elevated parathyroid and decreased calcitriol levels.Six patients (40%) did not survive to hospital discharge, compared with an overall CICU mortality rate of 2.6% (P < .01). The fracture case rate before implementation of the FBP was 2.6 cases/1000 admissions and was 0.7/1000 after implementation of the FBP (P = .04). CONCLUSIONS: Critically ill CHD patients are at risk for fractures. They represent a complex group who frequently has hyperparathyroidism and decreased calcitriol levels, and each may predispose to fractures. FBPs consisting of identification and careful patient handling should be considered in at-risk patients.
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Doenças Ósseas Metabólicas/etiologia , Fraturas Ósseas/etiologia , Cardiopatias Congênitas/complicações , Fatores Etários , Biomarcadores/sangue , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/terapia , Boston , Calcitriol/sangue , Protocolos Clínicos , Estado Terminal , Feminino , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/prevenção & controle , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/terapia , Mortalidade Hospitalar , Hospitais Pediátricos , Humanos , Hiperparatireoidismo/sangue , Hiperparatireoidismo/etiologia , Hiperparatireoidismo/terapia , Lactente , Mortalidade Infantil , Tempo de Internação , Masculino , Hormônio Paratireóideo/sangue , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
Congenital heart disease (CHD) patients are at risk for neurodevelopmental delay. The etiology of these delays is unclear, but abnormal prenatal cerebral maturation and postoperative hemodynamic instability likely play a role. A better understanding of these factors is needed to improve neurodevelopmental outcome. In this study, we used bedside frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) to assess cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle (SV) CHD undergoing surgery and compared them to controls. Our goals were 1) to compare cerebral hemodynamics between unanesthetized SV and healthy neonates, and 2) to determine if FDNIRS-DCS could detect alterations in cerebral hemodynamics beyond cerebral hemoglobin oxygen saturation (SO 2). Eleven SV neonates were recruited and compared to 13 controls. Preoperatively, SV patients showed decreased cerebral blood flow (CBFi ), cerebral oxygen metabolism (CMRO 2i ) and SO 2; and increased oxygen extraction fraction (OEF) compared to controls. Compared to preoperative values, unstable postoperative SV patients had decreased CMRO 2i and CBFi , which returned to baseline when stable. However, SO 2 showed no difference between unstable and stable states. Preoperative SV neonates are flow-limited and show signs of impaired cerebral development compared to controls. FDNIRS-DCS shows potential to improve assessment of cerebral development and postoperative hemodynamics compared to SO 2 alone.
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BACKGROUND: Cerebral blood flow velocity (CBFV) measured by transcranial Doppler sonography has provided information on cerebral perfusion in patients undergoing infant heart surgery, but no studies have reported a relationship to early postoperative and long-term neurodevelopmental outcomes. METHODS: CBFV was measured in infants undergoing biventricular repair without aortic arch reconstruction as part of a trial of hemodilution during cardiopulmonary bypass (CPB); CBFV (Vm, mean; Vs, systolic; Vd, end-diastolic) in the middle cerebral artery and change in Vm (rVm) were measured intraoperatively and up to 18 hours post-CPB. Neurodevelopmental outcomes, measured at 1 year of age, included the psychomotor development index (PDI) and mental development index (MDI) of the Bayley Scales of Infant Development-II. RESULTS: CBFV was measured in 100 infants; 43 with D-transposition of the great arteries, 36 with tetralogy of Fallot, and 21 with ventricular septal defects. Lower Vm, Vs, Vd, and rVm at 18 hours post-CPB were independently related to longer intensive care unit duration of stay (p<0.05). In the 85 patients who returned for neurodevelopmental testing, lower Vm, Vs, Vd, and rVm at 18 hours post-CPB were independently associated with lower PDI (p<0.05) and MDI (p<0.05, except Vs: p=0.06) scores. Higher Vs and rVm at 18 hours post-CPB were independently associated with increased incidence of brain injury on magnetic resonance imaging in 39 patients. CONCLUSIONS: Postoperative CBFV after biventricular repair is related to early postoperative and neurodevelopmental outcomes at 1 year of age, possibly indicating that low CBFV is a marker of suboptimal postoperative hemodynamics and cerebral perfusion.