Factors Associated With Mortality in Low-Risk Pediatric Critical Care Patients in The Netherlands.

Objective: To determine differences between survivors and nonsurvivors and factors associated with mortality in pediatric intensive care patients with low risk of mortality.

Design: Retrospective cohort study.

Setting: Patients were selected from a national database including all admissions to the PICUs in The Netherlands between 2006 and 2012.

The digestive tract as the origin of systemic inflammation.

Failure of gut homeostasis is an important factor in the pathogenesis and progression of systemic inflammation, which can culminate in multiple organ failure and fatality. Pathogenic events in critically ill patients include mesenteric hypoperfusion, dysregulation of gut motility, and failure of the gut barrier with resultant translocation of luminal substrates. This is followed by the exacerbation of local and systemic immune responses.

Neonatal thymectomy reveals differentiation and plasticity within human naive T cells.

The generation of naive T cells is dependent on thymic output, but in adults, the naive T cell pool is primarily maintained by peripheral proliferation. Naive T cells have long been regarded as relatively quiescent cells; however, it was recently shown that IL-8 production is a signatory effector function of naive T cells, at least in newborns. How this functional signature relates to naive T cell dynamics and aging is unknown.

Main pulmonary artery area limits exercise capacity in patients long-term after arterial switch operation.

Objectives: Despite excellent survival in patients after the arterial switch operation, reintervention is frequently required and exercise capacity is decreased in a substantial number of patients. This study relates right-sided imaging features in patients long-term after the arterial switch operation to exercise capacity and ventilatory efficiency to investigate which lesions are functionally important.

Methods: Patients operated in the UMC Utrecht, the Netherlands (1976-2001) and healthy controls underwent cardiac magnetic resonance imaging and cardiopulmonary exercise testing within 1 week.

The effect of short-term high versus normal protein intake on whole-body protein synthesis and balance in children following cardiac surgery: a randomized double-blind controlled clinical trial.

Background: Infants undergoing cardiac surgery are at risk of a negative protein balance, due to increased proteolysis in response to surgery and the cardiopulmonary bypass circuit, and limited intake. The aim of the study was to quantify the effect on protein kinetics of a short-term high-protein (HP) diet in infants following cardiac surgery.

Methods: In a prospective, double-blinded, randomized trial we compared the effects of a HP (5 g · kg(-1) · d(-1)) versus normal protein (NP, 2 g · kg(-1) · d(-1)) enteral diet on protein kinetics in children <24 months, on day 2 following surgical repair of congenital heart disease.

Minimizing the risk of preoperative brain injury in neonates with aortic arch obstruction.

Objective: To determine whether prenatal diagnosis lowers the risk of preoperative brain injury by assessing differences in the incidence of preoperative brain injury across centers.

Study Design: From 2 prospective cohorts of newborns with complex congenital heart disease studied by preoperative cerebral magnetic resonance imaging, one cohort from the University Medical Center Utrecht (UMCU) and a combined cohort from the University of California San Francisco (UCSF) and University of British Columbia (UBC), patients with aortic arch obstruction were selected and their imaging and clinical course reviewed.

Results: Birth characteristics were comparable between UMCU (n = 33) and UCSF/UBC (n = 54).

Nemaline myopathy caused byTNNT1 mutations in a Dutch pedigree.

Nemaline myopathy (NM) is genetically heterogeneous disorder characterized by early onset muscular weakness and sarcoplasmatic or intranuclear inclusions of rod-shaped Z-disk material in muscle fibers. Thus far, mutations in seven genes have been identified as cause of NM. Only one singleTNNT1 nonsense mutation has been previously described that causes autosomal recessive NM in the old order Amish with a very specific clinical phenotype including rapidly progressive contractures.

Mechanical ventilation drives inflammation in severe viral bronchiolitis.

Introduction: Respiratory insufficiency due to severe respiratory syncytial virus (RSV) infection is the most frequent cause of paediatric intensive care unit admission in infants during the winter season. Previous studies have shown increased levels of inflammatory mediators in airways of mechanically ventilated children compared to spontaneous breathing children with viral bronchiolitis. In this prospective observational multi-center study we aimed to investigate whether this increase was related to disease severity or caused by mechanical ventilation.

Tidal volume drives inflammation during mechanical ventilation for viral respiratory infection.

Objective: Respiratory syncytial virus lower respiratory tract infection is the most frequent cause of respiratory insufficiency necessitating mechanical ventilation in infants during the winter season. Recently, we presented a new animal model to show that mechanical ventilation aggravates respiratory syncytial virus-induced pulmonary inflammation by distinct mechanisms. We now use this model to study whether low tidal volume mechanical ventilation causes less ventilator-induced lung injury in the presence of respiratory syncytial virus lower respiratory tract infection.

Neurological injury after neonatal cardiac surgery: a randomized, controlled trial of 2 perfusion techniques.

Background: Complex neonatal cardiac surgery is associated with cerebral injury. In particular, aortic arch repair, requiring either deep hypothermic circulatory arrest (DHCA) or antegrade cerebral perfusion (ACP), entails a high risk of perioperative injury. It is unknown whether ACP results in less cerebral injury than DHCA.

Decreased expression of serum and microvascular vascular endothelial growth factor receptor-2 in meningococcal sepsis*.

Objectives: To determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis.

Design: Observational study.

Setting: Two tertiary academic children hospital PICUs.

Dexamethasone attenuates VEGF expression and inflammation but not barrier dysfunction in a murine model of ventilator-induced lung injury.

Background: Ventilator-induced lung injury (VILI) is characterized by vascular leakage and inflammatory responses eventually leading to pulmonary dysfunction. Vascular endothelial growth factor (VEGF) has been proposed to be involved in the pathogenesis of VILI. This study examines the inhibitory effect of dexamethasone on VEGF expression, inflammation and alveolar-capillary barrier dysfunction in an established murine model of VILI.

Mortality prediction models for pediatric intensive care: comparison of overall and subgroup specific performance.

Aim: To validate paediatric index of mortality (PIM) and pediatric risk of mortality (PRISM) models within the overall population as well as in specific subgroups in pediatric intensive care units (PICUs).

Methods: Variants of PIM and PRISM prediction models were compared with respect to calibration (agreement between predicted risks and observed mortality) and discrimination (area under the receiver operating characteristic curve, AUC). We considered performance in the overall study population and in subgroups, defined by diagnoses, age and urgency at admission, and length of stay (LoS) at the PICU.

Cerebral ischemia initiates an immediate innate immune response in neonates during cardiac surgery.

Background: A robust inflammatory response occurs in the hours and days following cerebral ischemia. However, little is known about the immediate innate immune response in the first minutes after an ischemic insult in humans. We utilized the use of circulatory arrest during cardiac surgery to assess this.

Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology.

Human respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract infections in infants and the elderly. In the vast majority of cases, however, RSV infections run mild and symptoms resemble those of a common cold. The immunological, clinical, and epidemiological profile of severe RSV infections suggests a disease caused by a virus with typical seasonal transmission behavior, lacking clear-cut virulence factors, but instead causing disease by modifying the host's immune response in a way that stimulates pathogenesis.

STAT3 regulates monocyte TNF-alpha production in systemic inflammation caused by cardiac surgery with cardiopulmonary bypass.

Background: Cardiopulmonary bypass (CPB) surgery initiates a controlled systemic inflammatory response characterized by a cytokine storm, monocytosis and transient monocyte activation. However, the responsiveness of monocytes to Toll-like receptor (TLR)-mediated activation decreases throughout the postoperative course. The purpose of this study was to identify the major signaling pathway involved in plasma-mediated inhibition of LPS-induced tumor necrosis factor (TNF)-α production by monocytes.

Low-flow antegrade cerebral perfusion attenuates early renal and intestinal injury during neonatal aortic arch reconstruction.

Objective: Deep hypothermic circulatory arrest (DHCA) and antegrade cerebral perfusion (ACP) are 2 cardiopulmonary bypass strategies mainly used in aortic arch reconstructions. It has been suggested that during ACP, abdominal organs are better protected than during DHCA owing to partial perfusion via collaterals. We tested this hypothesis using intraoperative near-infrared spectroscopy (NIRS), lactate measurements, and biomarkers for early abdominal injury in neonates undergoing complex aortic arch repair.

Host response to mechanical ventilation for viral respiratory tract infection.

Respiratory syncytial virus (RSV) bronchiolitis causes severe respiratory tract infection in infants, frequently necessitating mechanical ventilatory support. However, life-saving, mechanical ventilation aggravates lung inflammation. We set up a model to dissect the host molecular response to mechanical ventilation in RSV infection.

Bedside prediction rule for infections after pediatric cardiac surgery.

Purpose: Infections after pediatric cardiac surgery are a common complication, occurring in up to 30% of cases. The purpose of this study was to develop a bedside prediction rule to estimate the risk of a postoperative infection.

Methods: All consecutive pediatric cardiac surgery procedures between April 2006 and May 2009 were retrospectively analyzed.

Increasing duration of circulatory arrest, but not antegrade cerebral perfusion, prolongs postoperative recovery after neonatal cardiac surgery.

Objective: Deep hypothermic circulatory arrest (DHCA) and antegrade cerebral perfusion (ACP) are 2 cardiopulmonary bypass techniques applied in aortic arch repair. In recent literature, cerebral effects of both techniques have received most attention, whereas the consequences for other organs have not been thoroughly investigated. Therefore, in this study, the impact of duration of DHCA and ACP on postoperative recovery was analyzed in a cohort of neonates undergoing aortic arch reconstruction.

Long-term restoration of the human T-cell compartment after thymectomy during infancy: a role for thymic regeneration?

Thymectomy during early childhood is generally thought to have serious consequences for the establishment of the T-cell compartment. In the present study, we investigated the composition of the T-cell pool in the first 3 decades after thymectomy during infancy due to cardiac surgery. In the first 5 years after thymectomy, naive and total CD4(+) and CD8(+) T-cell numbers in the blood and T-cell receptor excision circle (TREC) levels in CD4(+) T cells were significantly lower than in healthy age-matched controls.

Intracranial bleeding due to vitamin K deficiency: advantages of using a pediatric intensive care registry.

Aim: To determine the incidence of late intracranial vitamin K deficiency bleeding (VKDB) in The Netherlands using the Dutch Pediatric Intensive Care Evaluation (PICE) registry.

Methods: The PICE registry was used to identify all infants who were admitted to a Dutch pediatric intensive care unit (PICU) with intracranial bleeding between 1 January 2004 and 31 December 2007. Cases of confirmed late intracranial VKDB were used to calculate the incidence for each year.