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INTRODUCTION: Cardiac surgery (CS) in pediatric patients induces an overt oxidative stress (OS) response. Children are particularly vulnerable to OS related injury. The immaturity of their organs and antioxidant systems as well as the induction of OS in cardio-pulmonary bypass (CPB) surgery may have an important impact on outcomes. The purpose of this study was to describe the OS response, measured by urinary free 8-iso-PGF2a, in infants undergoing CS and to evaluate the relationship between OS response and post-operative clinical outcomes. METHODS: Infants with congenital heart disease undergoing CS with or without CPB were eligible for enrollment. Children were classified as neonates (

The newborn rabbit is a useful animal model for various pathologies and procedures. Airway management of the rabbit is complex due to its anatomical characteristics, which is further complicated in the case of the newborn. Of the different methods of advanced airway management, endotracheal intubation is less aggressive than tracheostomy, and is more feasible than supraglottic management given the lack of supraglottic devices of such a small size. As direct glottis visualization is very difficult in animals this size, this blind intubation model is presented as an effective alternative, especially for experiments requiring prolonged anesthesia. Using this method, we performed blind intubations with a 90% success rate.

OBJECTIVES: To describe presentation, hospital course, and predictors of bad outcome in multisystem inflammatory syndrome in children (MIS-C). METHODS: Retrospective data review of a case series of children meeting the published definition for MIS-C who were discharged or died between March 1, 2020, and June 15, 2020, from 33 participating European, Asian, and American hospitals. Data were collected through a Web-based survey and included clinical, laboratory, electrocardiographic, and echocardiographic findings and treatment management. RESULTS: We included 183 patients with MIS-C: male sex, 109 (59.6%); mean age 7.0 ± 4.7 years; Black race, 56 (30.6%); obesity, 48 (26.2%). Overall, 114 of 183 (62.3%) had evidence of severe acute respiratory syndrome coronavirus 2 infection. All presented with fever, 117 of 183 (63.9%) with gastrointestinal symptoms, and 79 of 183 (43.2%) with shock, which was associated with Black race, higher inflammation, and imaging abnormalities. Twenty-seven patients (14.7%) fulfilled criteria for Kawasaki disease. These patients were younger and had no shock and fewer gastrointestinal, cardiorespiratory, and neurologic symptoms. The remaining 77 patients (49.3%) had mainly fever and inflammation. Inotropic support, mechanical ventilation, and extracorporeal membrane oxygenation were indicated in 72 (39.3%), 43 (23.5%), and 4 (2.2%) patients, respectively. A shorter duration of symptoms before admission was found to be associated with poor patient outcome and for extracorporeal membrane oxygenation and/or death, with 72.3% (95% confidence interval: 0.56-0.90; P = .006) increased risk per day reduction and 63.3% (95% confidence interval: 0.47-0.82; P < .0001) increased risk per day reduction respectively. CONCLUSIONS: In this case series, children with MIS-C presented with a wide clinical spectrum, including Kawasaki disease-like, life-threatening shock and milder forms with mainly fever and inflammation. A shorter duration of symptoms before admission was associated with a worse outcome.

Coronavirus disease 2019 (COVID-19) has affected patients across all age groups, with a wide range of illness severity from asymptomatic carriers to severe multi-organ dysfunction and death. Although early reports have shown that younger age groups experience less severe disease than older adults, our understanding of this phenomenon is in continuous evolution. Recently, a severe multisystem inflammatory syndrome in children (MIS-C), with active or recent COVID-19 infection, has been increasingly reported. Children with MIS-C may demonstrate signs and symptoms of Kawasaki disease, but also have some distinct differences. These children have more frequent and severe gastrointestinal symptoms and are more likely to present with a shock-like presentation. Moreover, they often present with cardiovascular involvement including myocardial dysfunction, valvulitis, and coronary artery dilation or aneurysms. Here, we present a review of the literature and summary of our current understanding of cardiovascular involvement in children with COVID-19 or MIS-C and identifying the role of a pediatric cardiologist in caring for these patients.

INTRODUCTION: Right ventricular (RV) dilatation is the determining prognostic factor in the long-term follow up of patients with repaired Tetralogy of Fallot (TOF). The objective of this study is to analyze whether the results vary depending on the timing of the complete repair and on the surgical technique applied. MATERIAL-METHODS: This is a retrospective longitudinal study in which patients with standard TOF were divided into 3 groups depending on their age at surgical repair: group 1 = Early repair (n = 12,1-8 months), group 2 = Late repair (n = 26, > 8 months), and group 3 = Late repair with previous palliative surgery (n = 17, > 8 months). Clinical, echocardiographic and cardiac magnetic resonance (CMR) data from patients that had received complete reparative surgery in our institution from January 2000 to March 2014 were analyzed and compared. RESULTS: 55 patients with echocardiogram and CMR studies (13.39 ± 3.59 years) were reviewed. All patients had at least moderate pulmonary regurgitation (PR). We observed a positive correlation between PR and right ventricular end-diastolic volume (r(2) = 0.418; p = 0,004). Group 3 had more severe right ventricular dilatation than patients in groups 1 and 2 (p = 0.001). No differences in right ventricular end-diastolic volume, PR, and pulmonary trunk dimensions were observed between groups 1 and 2. Patients in group 3 had a longer hospital stay. CONCLUSIONS: Although all patients from our cohort had significant PR, age at surgery was not related to RV or pulmonary trunk dilatation. Previous palliative surgery was associated with more severe right ventricular dilatation and longer hospital stays. No differences were observed between early and late repair groups. Our study suggests that postponing TOF repair to a late stage does not improve the degree of PR or long-term morbidity from RV dilatation. Palliative surgery should be avoided if possible.

Non-compacted cardiomyopathy (NCM) is a heterogenous myocardial disorder. Although much has been published in recent years, little is known about NCM in the neonatal period. The objective of this study is to characterize the involvement of newborns affected with NCM and to identify risk factors associated with increased mortality. This is a retrospective study including all neonates diagnosed with NCM between 2006 and 2018. Diagnosis was based on echocardiographic findings. Data were collected regarding prenatal history, gestational age and weight at birth, gender, age at diagnosis, left or biventricular involvement and associated malformations, medical and surgical treatments, and evolution. Fourteen patients were included. The median follow-up duration was 34 months (range 1-87 months). The left ventricular apex and lateral wall were involved in all cases (100%). Thirteen patients (92.8%) had other associated heart malformations. Six patients (42.8%) died during the follow-up period. Patients who had biventricular involvement and poor ventricular function presented a higher risk of death. The main cause of death was ventricular dysfunction (5/6 [83.3%]). During follow-up, eight patients (57.1%) underwent surgery for their cardiac malformations, without higher mortality. NCM must be included in the differential diagnosis of neonatal cardiomyopathy. The higher mortality observed in our series is related not only to the high association with congenital heart disease, but also to a greater presence of early and severe left ventricular dysfunction. We did not find that patients who underwent surgery with cardiopulmonary bypass had worse outcomes.

To improve the understanding of the pathophysiology of transposition of the great arteries with intact ventricular septum (TGA/IVS) and the cardiac remodeling occurring from fetal to neonatal life, we performed a morphometric and functional echocardiographic assessment in fetuses and newborns. This was a prospective case-control study performed in a tertiary referral center, which included fetuses and newborns with a diagnosis of TGA/IVS between 2011 and 2018. Morphometry and systolic and diastolic function parameters were compared with age and body surface-matched healthy controls. Twenty-one TGA/IVS patients were included during the study period and morphometric and functional echocardiographic data were recorded. TGA/IVS patients showed morphometric and functional changes of increased overall volume and output, predominantly in the aortic component from fetus to newborn, probably due to compensatory mechanisms secondary to brain hypoxia.

BACKGROUND: Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children. METHODS: Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. AGREE statement was followed to prepare this document. RESULTS: Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C). CONCLUSIONS: Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.

Background During the SARS-CoV2 pandemic, there has been increase in hyperinflammatory presentation in previously healthy children with a variety of cardiac manifestations. Our objective is to describe the cardiac manifestations found in an international cohort of 55 pediatric cases with multi-system inflammatory syndrome (MIS-C) during the SARS-CoV2 pandemic. Methods and Results We reviewed data on previously healthy pediatric patients (=18 years) with structurally normal hearts who presented at hospitals in the United States, United Kingdom, Spain and Pakistan with MIS-C and had consultation with a pediatric cardiologist. Data collected included demographics, clinical presentation, laboratory values, electrocardiographic abnormalities, echocardiographic findings and initial therapies. A total of 55 patients presented with MIS-C. Thirty-five patients (64%) had evidence of decreased left ventricular function, 17 (31%) had valvulitis, 12 (22%) with pericardial effusion and 11 (20%) with coronary abnormalities. Twenty-seven (49%) required ICU admission and 24 (44%) had evidence of shock. Eleven patients (20%) fulfilled complete Kawasaki disease criteria and had lower NT pro-BNP, D-dimer and ferritin levels compared with those who did not fulfill criteria. Electrophysiologic abnormalities occurred in 6 patients and included complete atrioventricular (AV) block, transient AV block and ventricular tachycardia. Conclusions We describe the first international cohort of pediatric patients with MIS-C during the SARS-CoV2 pandemic with a range of cardiac manifestations. This paper brings awareness and alertness to the global medical community to recognize these children during the pandemic and understand the need for early cardiology evaluation and follow-up.

INTRODUCTION: Persistent pulmonary hypertension of the newborn (PPHN) is a neonatal syndrome associated with significant morbidity and mortality that is caused by the failure of postnatal drop in pulmonary vascular resistance. In extreme cases, patients may require extracorporeal membrane oxygenation therapy (ECMO). The aim of this study was to explore lung ultrasound (LUS) patterns in newborns with PPHN requiring ECMO. PATIENTS AND METHODS: From January 2014 to January 2018, LUS was performed on patients with PPHN admitted for ECMO treatment. PPHN diagnosis was based on clinical and echocardiographic findings. LUS was performed before patients underwent ECMO cannulation. An underlying diagnosis was made taking into account the patient's complete medical history, excluding LUS information. A blinded physician, unaware of the patient's clinical condition, analyzed the stored ultrasound images. Results were then compared with chest x-ray (CXR) diagnoses. RESULTS: Seventeen patients were recruited; 12 were male (70.6%). The median gestational age was 38.7 weeks, with 13 term newborns (76.5%). Twelve were cannulated for VA ECMO, with a median ECMO run of 111.2 h. Six patients (35%) survived. Patients with alveolar capillary dysplasia with misaligned pulmonary veins, fetal ductus arteriosus constriction, or sepsis had normal LUS patterns (A-lines with lung sliding). LUS showed a better sensitivity (88.9%) and specificity (85%) than CXR (55.6 and 77.5%, respectively) in identifying patients with nonparenchymal lung disease. CONCLUSIONS: LUS can provide essential information to help diagnose the underlying cause of PPHN in an earlier and more effective way than CXR. LUS is suitable for routine utilization in the intensive care unit.

AIM: Nasal cannulas are used to provide oxygen support for infants and have been considered as a means for delivering aerosols to the lungs. To measure mucociliary clearance in the lungs of infants with congenital heart defects, we delivered radiopharmaceutical aerosols via a nasal cannula. Here we report on the pulmonary and nasal deposition of these aerosols. METHOD: A total of 18 infants (median age = 26 days; quartiles = 11-74 days) performed clearance measurements soon before or after corrective cardiac surgery. The regional aerosol deposition was assessed using gamma camera imaging. RESULTS: Cannula flow rate significantly affected pulmonary dosing. Flow rates useful for oxygen support were associated with low pulmonary deposition (2 L/min; mean, 4.5% of deposited dose; range, 2%-9%; n = 7) and high nasal deposition. Much lower cannula flow rates increased the pulmonary deposition (0.2 L/min; mean, 33.5% of deposited dose; range, 15%-51%; n = 5; P = 0.005 vs 2 L/min). The ratio of nose/lung dosing was approximately 26:1 at 2 L/min and 2:1 at 0.2 L/min. Bench studies demonstrated cannula output rates of 10.2 ± 1.7% (2 L/min) and 3.3 ± 0.4% (0.2 L/min) of the loaded nebulizer dose during a 2-minute delivery. Combining in vitro and in vivo results, we estimate that 0.46% of the loaded nebulizer dose reaches the lungs at 2 L/min vs 1.10% at 0.2 L/min during a 2-minute delivery. CONCLUSION: With the delivery system used here, pulmonary aerosol delivery via nasal cannula was very inefficient at the flow rates required to provide oxygen support. Even at low flows, nasal deposition was substantial and local toxicity must be considered.

OBJECTIVES: Examine the relationship between perioperative renal regional tissue oximetry, urinary biomarkers, and acute kidney injury in infants after congenital cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, observational. SETTING: Cardiac operating room and cardiac ICU. PATIENTS: Neonates and infants without history of kidney injury or anatomic renal abnormality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Renal regional tissue oximetry was measured intraoperatively and for 48 hours postoperatively. Urinary levels of neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloproteinases 2 together with insulin-like growth factor-binding protein 7 were measured preoperatively, 2, 12, and 24 hours postoperatively. Patients were categorized as no acute kidney injury, stage 1, or Stage 2-3 acute kidney injury using the Kidney Disease: Improving Global Outcomes criteria with 43 of 70 (61%) meeting criteria for any stage acute kidney injury. Stage 2-3 acute kidney injury patients had higher tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7 at 2 hours (0.3 vs 0.14 for stage 1 acute kidney injury and 0.05 for no acute kidney injury; p = 0.052) and 24 hours postoperatively (1.71 vs 0.27 for stage 1 acute kidney injury and 0.19 for no acute kidney injury, p = 0.027) and higher neutrophil gelatinase-associated lipocalin levels at 24 hours postoperatively (10.3 vs 3.4 for stage 1 acute kidney injury and 6.2 for no acute kidney injury, p = 0.019). Stage 2-3 acute kidney injury patients had lower mean cardiac ICU renal regional tissue oximetry (66% vs 79% for stage 1 acute kidney injury and 84% for no acute kidney injury, p = 0.038). Regression analyses showed that tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7 at 2 hours postoperatively and nadir intraoperative renal regional tissue oximetry to be independent predictors of postoperative kidney damage as measured by urinary neutrophil gelatinase-associated lipocalin. CONCLUSIONS: We observed modest differences in perioperative renal regional tissue oximetry and urinary biomarker levels compared between acute kidney injury groups classified by creatinine-dependent Kidney Disease: Improving Global Outcomes criteria, but there were significant correlations between renal regional tissue oximetry, tissue inhibitor of metalloproteinases 2, insulin-like growth factor-binding protein 7, and postoperative neutrophil gelatinase-associated lipocalin levels. Kidney injury after infant cardiac surgery may be undetectable by functional assessment (creatinine) alone, and continuous monitoring of renal regional tissue oximetry may be more sensitive to important subclinical acute kidney injury.

Indications for extracorporeal membrane oxygenation (ECMO) and extracorporeal cardiopulmonary resuscitation (ECPR) are expanding, and echocardiography is a tool of utmost importance to assess safety, effectiveness and readiness for circuit initiation and separation. Echocardiography is key to anticipating complications and improving outcomes. Understanding the patient's as well as the ECMO circuit's anatomy and physiology is crucial prior to any ECMO echocardiographic evaluation. It is also vital to acknowledge that the utility of echocardiography in ECMO patients is not limited to the evaluation of cardiac function, and that clinical decisions should not be made exclusively upon echocardiographic findings. Though echocardiography has specific indications and applications, it also has limitations, characterized as: prior to and during cannulation, throughout the ECMO run, upon separation and after separation from the circuit. The use of specific and consistent echocardiographic protocols for patients on ECMO is recommended.

Neonates with complex congenital heart disease (CHD) demonstrate microstructural brain dysmaturation, but the relationship with structural network topology is unknown. We performed diffusion tensor imaging (DTI) in term neonates with CHD preoperatively (N = 61) and postoperatively (N = 50) compared with healthy term controls (N = 91). We used network topology (graph) analyses incorporating different weighted and unweighted approaches and subject-specific white matter segmentation to investigate structural topology differences, as well as a voxel-based analysis (VBA) to confirm the presence of microstructural dysmaturation. We demonstrate cost-dependent network inefficiencies in neonatal CHD in the pre- and postoperative period compared with controls, related to microstructural differences. Controlling for cost, we show the presence of increased small-worldness (hierarchical fiber organization) in CHD infants preoperatively, that persists in the postoperative period compared with controls, suggesting the early presence of brain reorganization. Taken together, topological microstructural dysmaturation in CHD infants is accompanied by hierarchical fiber organization during a protracted critical period of early brain development. Our methodology also provides a pipeline for quantitation of network topology changes in neonates and infants with microstructural brain dysmaturation at risk for perinatal brain injury.

OBJECTIVES: To identify patient- and disease-related factors related to survival and favorable outcomes for children who underwent extracorporeal cardiopulmonary resuscitation after a refractory cardiac arrest. DESIGN: Retrospective observational study with prospective assessment of long-term functional outcome. PATIENTS: Fifty-six consecutive children undergoing extracorporeal cardiopulmonary resuscitation at our institution from 2007 to 2015. Median age at arrest was 3.5 months (interquartile range, 1-53). SETTING: Tertiary pediatric university hospital with a referral heart center. INTERVENTIONS: Health-related quality of life and family functioning assessment with the Pediatric Quality of Life Inventory and the McMaster Family Assessment Device. MEASUREMENTS AND MAIN RESULTS: Fifty-eight consecutive extracorporeal cardiopulmonary resuscitation episodes were included, with 46 (79.3%) related to primary cardiac conditions. Initial cannulation site was central in 19 (32.8%) and peripheral in 39 (67.2%). Survival to decannulation was 77.6% with survival at hospital discharge and at the end of the follow-up period being 65.5% and 62.1%, respectively. Time to follow-up was 38 months (interquartile range, 19-52). Patients who survived tended to be younger (3.5 mo [1 mo to 2 yr] vs 7 mo [1.25 mo to 17 yr]; p = 0.3) with decreased extracorporeal cardiopulmonary resuscitation times (28 min [15-47 min] vs 37.5 min [28.5-55 min]; p = 0.04). Those who received therapeutic hypothermia tended to have higher hospital survival (21/28 [75%] vs 16/29 [55%]; p = 0.08). Follow-up assessments of survivors demonstrated good quality of life and family functioning (Pediatric Quality of Life Inventory, 84 [76-89.5]; McMaster Family Assessment Device, 1.62 [1.33-1.83]). CONCLUSIONS: In this series, extracorporeal cardiopulmonary resuscitation was associated with relatively high survival rates and a good health-related quality of life and family functioning. Larger series are needed to assess whether this technique should be more broadly available in the pediatric critical care community.

BACKGROUND: Newborns with congenital heart disease have associated brain damage that affects short-and long-term neurodevelopment. Several neuronal biomarkers exist that could predict brain damage. We investigated the pattern of neuron-specific enolase (NSE) and s100B levels after cardiopulmonary bypass surgery in neonates with congenital heart disease. METHODS: We completed a prospective observational study of neonates with congenital heart disease who were undergoing cardiopulmonary bypass surgery. NSE and s100B levels were measured from serum samples obtained preoperatively, immediately postoperatively, and once daily on postoperative days one to seven. Cranial ultrasounds were obtained preoperatively and postoperatively and findings were scored using an internally developed scoring system. RESULTS: Eighteen neonates were included. Immediate postoperative and peak levels of both NSE (58.0 [21.6] and 68.1 [55.7] µg/L) and s100B (0.14 [0.3] and 0.14 [0.3] µg/L) were significantly increased when compared with preoperative levels (34.0 [21.6] µg/L; P

Expression of Tyrosine Hydroxylase (TH) is frequently seen in neuroblastomas, the most common extracranial tumor in children, and TH mRNA detection is used for the analysis of microcirculating or micrometastatic disease in this neoplasia. TH is known to have at least seven isoforms produced by alternative splicing of the N-terminal region (exons 1-4), although no other splicing variants have been described downstream. TH expression was analyzed in six samples of neuroblastoma by RT-PCR using highly restrictive conditions and primers between exons 5 and 12, a region of the gene previously considered to be constant. In the analyzed samples we found two novel TH mRNAs, one lacking exon 8, and another lacking exons 8+9. These new splicing variants are described in a region of TH previously reported to be conserved, and that has been used for the design of reverse transcriptase-polymerase chain-reaction assays for the detection of minimal residual disease [Eur. J. Cancer, 27 (1991) 762]. The splicing pattern characteristic of every tumor could allow the monitoring of the minimal residual disease in a tumor-specific manner.

Neuroblastomas, the most common extracranial solid tumors in children, present an extremely heterogeneous behaviour that can be explained in part by their genetic abnormalities. Thirty-four patients treated at the Pediatric Oncology Unit, Hospital Vall d'Hebron from 1993 to 1997 were prospectively studied to determine the relative prognostic impact of a number of clinical and molecular factors. The factors studied were: ploidy, MYCN and 1p status, and TRK-A expression, in addition to age, stage and histology. Their impact on prognosis was analyzed. In univariate analysis, advanced stage, unfavorable histology, diploidy, MYCN amplification, and 1p deletion were identified as adverse prognostic factors; TRK-A expression was associated with favorable prognosis. After multivariate analysis, only MYCN amplification proved to be an independent adverse prognostic factor (p=0.03), whereas TRK-A expression identified a subset of good-prognosis patients (p=0.003).