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Purpose: To test the hypothesis that RNA editing is altered in pediatric patients with cyanotic congenital heart disease (CHD) and to determine whether A-to-I RNA editing is associated with the postoperative course following cardiac surgery. Cyanotic CHD is associated with a unique pathophysiology caused by chronic hypoxia. The perioperative course of cyanotic infants is partly dictated by the degree of expression of inflammatory and cardiac genes, some of which undergo A-to-I RNA editing. Methods: RNA was extracted pre- and postoperatively from blood samples of cyanotic and acyanotic patients. Each sample was analyzed for A-to-I RNA editing using automatic DNA sequencing of an intronic segment of the MED13 gene. RNA expression levels of adenosine deaminase acting on RNA (ADAR) enzymes responsible for RNA editing were examined by quantitative reverse-transcriptase polymerase chain reaction. Results: A-to-I RNA editing in MED13 was significantly higher among cyanotic patients ( n = 19) than acyanotic ones ( n = 18) both pre- and postoperatively, as manifested by average editing at seven highly edited sites (27.4 ± 8.5% versus 20.8 ± 10.2%; P = 0.038) and editing at specific sites, e.g., position 14 (20.2 ± 5.1% versus 14.5 ± 5.2%; P = 0.002). Cyanotic patients exhibited a more complicated postoperative course than acyanotic patients. ADAR2 RNA levels were significantly lower among cyanotic patients. Conclusions: Cyanotic children manifest significantly higher rates of A-to-I RNA editing than acyanotic children as well as a more complicated surgical course. Posttranscriptional RNA changes may affect cellular and metabolic pathways and influence the perioperative course following hypoxia. [ABSTRACT FROM AUTHOR]

This study aimed to examine the association between lactate levels in the first hours after surgery for congenital heart defects and the results of Risk-Adjusted Classification for Congenital Heart Surgery (RACHS-1) scoring and to evaluate serial lactate levels over time to determine whether they can serve as a supplementary tool for postoperative assessment within the same RACHS-1 group of patients. A retrospective cohort study was performed using data retrieved from a clinical database of 255 children who had surgery for congenital heart defects between 1999 and 2001 at Sheba Medical Center. Lactate levels were measured postoperatively four times (mg/dL units). The last sample was taken at the end of the surgical procedure, and lactate levels were measured at admission to the pediatrics critical care unit, then 6 and 12 h after admission. The lactate level was measured via arterial blood gases. A total of 27 deaths occurred, yielding a mortality rate of 7.4% when Norwood operations were excluded and 10.16% when they were included. The mean initial postoperative lactate level was significantly lower for survivors (42.2 ± 32.0 mg/dL) than for nonsurvivors (85.4 ± 54.1 mg/dL) ( p < 0.01). The serial mean lactate levels decreased progressively for all surviving patients ( r = 0.96) compared with nonsurvivors ( r = 0.02). The lactate levels correlated with the RACHS-1 subgroups at each time point ( r > 0.96 for all). The Pearson correlations between postoperative lactate levels (last lactate measurement taken in the operating room) and cardiopulmonary bypass (CPB) duration ( r = 0.549), clamp duration ( r = 0.586), and the inotropic score ( r = 0.466) ( p < 0.001 for all) were significantly positive. The correlations between the maximum lactate levels (during the first 12 postoperative hours) and CPB duration ( r = 0.496), clamp duration ( r = 0.509), and the inotropic score ( r = 0.633) ( p < 0.001 for all) were extremely positive. The early elevation of lactate levels in RACHS-1 subgroups 1 to 3 were highly correlated with poor prognosis and death ( p < 0.03). In addition, the lactate levels differed significantly between survivors and nonsurvivors within the same RACHS-1 subgroup. The survivors in RACHS-1 subgroups 1 to 3 had lower mean lactate levels than the nonsurvivors in this group ( P = 0.011), and this also held true for the survivors and nonsurvivors in RACHS-1 subgroups 4 to 6 ( P = 0.026). Lactate levels differed significantly between survivors and nonsurvivors within the same RACHS-1 subgroup. This combination allows the targeting of appropriately intensive interventions and therapies toward the sickest patients. [ABSTRACT FROM AUTHOR]

Objective: The admission of patients with cystic fibrosis (CF) to the intensive care unit (ICU) is controversial. Our aim was to study the long-term outcome of patients with CF who were admitted to the ICU and the effect of ventilation modality. Methods: The medical records of 104 admissions (1996-2006) of 48 patients with CF (age 18±9 years) were reviewed. Seventeen patients were admitted with reversible conditions (group 1). Thirty-one patients were admitted for acute on chronic respiratory failure (group 2). Results: In group 1, 16 of 17 patients survived up to 10 years from ICU admission. Conversely, in group 2, 23 of 31 patients (74%) died of respiratory failure. In group 2, 17 of 18 patients who were mechanically ventilated died within 90 days from admission, and 7 of 10 patients treated for prolonged periods with bi-level positive airway pressure are still alive up to 10 years after admission and transplantation. Conclusion: Patients requiring mechanical ventilation may have a poor prognosis. The outcome of treatment with bi-level positive airway pressure is good, even in patients who had many episodes of acute respiratory failure. [Copyright &y& Elsevier]

Abstract: Purpose: Leptin and interleukin-6 (IL-6) are inversely correlated and associated with decreased survival in critically ill patients. We investigated changes in leptin, IL-6, and troponin in children undergoing open-heart surgery, hypothesizing that IL-6 and troponin will increase after cardiopulmonary bypass (CPB) and will be negatively correlated with leptin. Patients and Methods: Serial blood samples were collected from 21 patients 24 hours before and up to 48 hours after surgery. Results: Leptin levels decreased by 50% during CPB (P < .001), then gradually increased, reaching baseline levels 12 hours after surgery. The IL-6 levels increased (P < .001) during CPB, peaking 2 hours after surgery and remaining slightly elevated at 24 hours after surgery (P < .001). Leptin and IL-6 were negatively correlated (R = −0.448, P < .001). Troponin levels increased during CPB (P < .001). Postoperative leptin and troponin were inversely correlated (r = −0.535, P < .001). Patients with modest elevations in troponin levels (<20 μg/L) had a shorter aortic clamp and CPB time (P < .01), lower IL-6 peak levels (P = .03), and shorter duration of ventilation and inotropic support compared with patients with peak troponin levels greater than 20 μg/L. Conclusions: Lower leptin and higher IL-6 levels correlated with troponin, a marker of myocardial injury. Because leptin may have cardioprotective effects, the postoperative drop in its levels may further contribute to myocardial dysfunction. [Copyright &y& Elsevier]

Pulmonary hypertension is characterised by a progressive increase in pulmonary vascular resistance and a poor prognosis. The exact underlying mechanisms are still poorly understood; however, it is hypothesised that pulmonary medial hypertrophy and endothelial dysfunction lead to impaired production of vasodilators such as nitric oxide (NO) and prostacyclin, and increased expression of vasoconstrictors such as endothelin-1. The current treatment modalities for pulmonary hypertension include conventional supportive therapies and more specific pharmacological therapies that are targeted at abnormalities of endothelial function. NO and phosphodiesterase type 5 (PDE5) inhibitors induce pulmonary vasodilation by increasing intracellular cyclic guanosine monophosphate (cGMP) concentrations.Sildenafil citrate is a highly selective inhibitor of PDE5. Investigations in animal models and recent clinical case reports with some studies in the paediatric population suggest that sildenafil may be a promising agent in treating pulmonary hypertension. The effect of sildenafil on pulmonary vasculature appears to be independent of the underlying cause, thereby providing a role in idiopathic pulmonary arterial hypertension (PAH), PAH associated with congenital heart disease, pulmonary hypertension secondary to lung disease or persistent pulmonary hypertension of the newborn. It may also be beneficial in postoperative pulmonary hypertension and in neonates who are difficult to wean from inhaled NO. It is easily administered and effective, and has minimal systemic adverse effects. Although the reported results in children with pulmonary hypertension are promising, it is an experimental drug and large-scale randomised controlled studies are required to validate the safety, efficacy and dosage in the paediatric population. [ABSTRACT FROM AUTHOR]

Background: Diffuse alveolar hemorrhage (DAH) is a frequent life-threatening complication of bone marrow transplantation (BMT) in adults. This noninfectious pulmonary disorder is rarely reported following BMT in neonates and children. Study objectives: To review the clinical features and course of children who underwent allogeneic BMT and developed DAH in the posttransplant period. Design: A retrospective 6-year chart review. Setting: Pediatric ICU in a university hospital. Patients and interventions: At total of 138 children who had undergone allogeneic BMT for nonmalignant (n = 66) or malignant (n = 72) diseases. Measurements and results: Six of 138 children (4.3%) aged 2 months to 10 years (male/female ratio, 1:1) developed DAH. Each had a fulminant course with rapidly developing severe respiratory failure, mandating mechanical ventilation within 24 h following symptom onset. They were all treated with methylprednisolone, 6 mg/kg/d for 3 days. Only one child survived, and there have been no sequelae at 2 years post-BMT. Four children died of respiratory causes, and one died of multiorgan failure. Conclusions: DAH is a potentially fatal respiratory complication that should be included early in the differential diagnosis of acute respiratory failure in children following allogenic BMT for both malignant and nonmalignant diseases. Therapy with high doses of steroids apparently do not affect the course of the disease. [ABSTRACT FROM AUTHOR]

Abstract: Lung transplantation (Tx) is an optional treatment for cystic fibrosis (CF) patients with end-stage lung disease. The decision to place a patient on the Tx waiting list is frequently complex, difficult, and controversial. This study evaluated the current criteria for lung Tx and assessed additional parameters that may identify CF patients at high risk of death. Data were extracted from the medical records of 392 CF patients. Forty of these patients had a forced expiratory volume in 1 s (FEV 1 ) less than 30% predicted, and nine of these 40 patients were transplanted. A comparison was performed between the survival of those transplanted (n = 9) and those not transplanted (n = 31), by means of Kaplan–Meier survival curves. The influence on survival of age, gender, nutritional status, sputum aspergillus, diabetes mellitus, recurrent hemoptysis, oxygen use, and the decline rate of FEV 1 , were investigated by means of univariate and multivariate analyses. The rate of decline of FEV 1 was evaluated employing the linear regression model. CF patients with a FEV 1 < 30% and who did not receive a lung transplant had survived longer than CF patients who did receive a lung transplant (median survival 7.33 vs. 3.49 yr, 5-yr survival 73% vs. 29%). Two factors – rate of decline in FEV 1 values and age < 15 yr – were found to influence the mortality rate, while the other parameters examined did not. Our results indicate that the current criterion of FEV 1 < 30% predicted, alone is not sufficiently sensitive to predict the mortality rate in CF patients and time of referral for Tx, as many of these patients survive for long periods of time. Additional criteria to FEV 1 < 30%, should include rapidly declining FEV 1 values and age < 15 yr. [ABSTRACT FROM AUTHOR]

Acute epidural hematoma (AEH), a relatively common complication of head injury in children, persists in bearing high morbidity and mortality. Early establishment of prognosis could guide optimal patient allocation, and early identification of predictive signs could assist in choosing appropriate therapeutic interventions. This study aimed to delineate expeditiously obtainable prognostic markers for determining outcome in a subset of children with AEH. We reviewed our 11-year experience with 61 consecutive children <16 years old with head trauma and isolated AEH. Treatment followed a standard advanced trauma life support protocol. A medical history was obtained, and all patients underwent neurosurgical and physical evaluations. CT scans were performed, as were laboratory tests which included arterial blood gases, glucose, electrolytes (K[sup +] , Na[sup +] ), hemoglobin and coagulation studies. Evaluation of the data collected on cause of injury, interval between trauma occurrence and presentation, clinical symptoms, Glasgow Coma Scale (GCS) scores, vital signs, laboratory test results, physical findings and surgical versus conservative management revealed that the best single predictors of outcome following AEH were the GCS and focal neurological deficits. Of all laboratory data obtained on admission, the blood potassium, pH and glucose test results correlated significantly with prognosis. Prognosis can be adequately and expeditiously estimated by selected markers within a comprehensive evaluation of children with AEH.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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Objective: Traditionally, pediatric tracheostomy has been viewed as a technically demanding procedure with a high complication rate, requiring the routine use of a formal operating room. Pediatric bedside tracheostomy in an intensive care unit (ICU) setting has not been widely reported, in contrast to the widespread adult bedside ICU tracheostomy. Transport of these critically ill, multiple life support systems dependent patients can be technically difficult, labor intensive, and potentially risky for these patients. Our study aimed to demonstrate the safety and efficacy of bedside tracheostomy in the pediatric ICU. Materials and Methods: A retrospective analysis of all pediatric patients undergoing tracheostomy at a tertiary care center, between 1st of January 2013 and 31st of December 2019. Results: During the study period, 117 pediatric patients underwent tracheostomy, 57 (48.7%) were performed bedside while 60 (51.3%) were performed in the operating room. Patients' ages ranged from 2 weeks to 17 years of age, with a median age of 16 months. No case of bedside tracheostomy necessitated a shift to the operating room. There was no difference in 30-day morbidity and mortality between the 2 groups. Conclusions: Our results suggest that pediatric open bedside tracheostomy in an ICU setting is a safe procedure, with similar complications and outcomes compared to tracheostomy performed in the operating room. [ABSTRACT FROM AUTHOR]