B-acute Lymphoblastic Leukemia With Hypereosinophilia Associated With Severe Cardiac Complications: A Clinical Case.

Hypereosinophilia (HE) is rare but often secondary to a nonhematologic disease such as allergic disorders and parasitic infections. HE can also be associated with hematologic malignancies and be the result of a clonal proliferation or reactive to another hematologic condition. Association of HE with acute lymphoblastic leukemia (ALL) is rare in children. We reported a case of a teenager presented with HE secondary to B-ALL who experienced severe cardiac complications with severe absolute eosinophil count. We compared his clinical evolution with other published cases and we reported 2 mutations linked to B-ALL never described before in this context.

Combined Use of Rotational Thromboelastometry (Rotem) and Platelet Impedance Aggregometry (Multiplate Analyzer) in Cyanotic and Acyanotic Infants and Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass: Subgroup Analysis of a Randomized Clinical Trial.

OBJECTIVES: Few studies have investigated the Multiplate platelet function analyzer in pediatrics. The authors evaluated Multiplate combined with Rotem in terms of guiding platelet transfusion after pediatric cardiac surgery with cardiopulmonary bypass (CPB). The authors further compared coagulation parameters between cyanotic and acyanotic patients. DESIGN: Subgroup analysis of a randomized clinical trial. SETTING: Tertiary hospital. PARTICIPANTS: Patients weighing between seven and 15 kg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Rotem and Multiplate tests were performed (1) after anesthesia induction, (2) upon CPB separation, and (3) upon intensive care unit arrival. Among a total of 59 subjects, 9 patients required platelet transfusion. In multivariate linear regression, analysis EXTEM maximum clot firmness upon CPB separation was associated with the volume of transfused platelets (regression coefficient = -0.348 [95% confidence interval -1.006 to -0.028]; p = 0.039). No such association was found for the Multiplate test. Acyanotic and cyanotic heart disease were present in 32 and 27 children, respectively. There were no significant differences between these two groups in terms of platelet count and function. Postoperative blood loss was significantly higher in the cyanotic group compared with the acyanotic arm (p = 0.015; difference [95% confidence interval -2.40 {-4.20 to -0.60}]). There were no differences between groups regarding transfusion of allogeneic blood products. CONCLUSIONS: This study showed that Rotem, but not Multiplate results, were associated with platelet transfusion in pediatric cardiac surgery with no intake of platelet inhibitors. The usefulness of combining these tests in platelet transfusion decision-making needs to be evaluated in larger populations.

Typical or Atypical Hemolytic Uremic Syndrome and the Use of Eculizumab: 4 Illustrative Cases.

Typical hemolytic uremic syndrome (HUS) in children is caused mostly by Escherichia coli 0157:H7 in our country. Atypical HUS (aHUS) causes include Streptococcus pneumoniae, methyl malonic aciduria, deficiency of ADAMST 13, and genetic or acquired disorder of the complement. Treatment of HUS relies on supportive measures while treatment of aHUS includes plasmapheresis and specific treatments. Recently, eculizumab has been proposed for the treatment of aHUS and many clinicians now believe that eculizumab should be the first-line standard of care. The purpose of this article is to illustrate the difficulties in the diagnostic process of HUS and therefore the subsequent problem to promptly choose the appropriate treatment. To date, workup of HUS continues to take many days leaving the clinicians with a choice between several therapeutic options. With the emergence of eculizumab, it becomes crucial to find faster diagnostic tools and to adapt HUS treatment protocols. We reported here clinical cases where eculizumab use was probably not appropriate once the correct diagnosis of typical HUS was made and cases where it would have been useful because of the late diagnosis of aHUS.

Novel insights into the assessment of risk of upper gastrointestinal bleeding in decompensated cirrhotic children.

OBJECTIVES: Cirrhotic children wait-listed for liver transplant are prone to bleeding from gastrointestinal varices. Grade 2-3 esophageal varices, red signs, and gastric varices are well-known risk factors. However, the involvement of hemostatic factors remains controversial because of the rebalanced state of coagulation during cirrhosis. METHODS: Children suffering from decompensated cirrhosis were prospectively included while being on waitlist. Portal hypertension was assessed by ultrasound and endoscopy. Coagulopathy was evaluated through conventional tests, thromboelastometry, and platelet function testing. The included children were followed up until liver transplantation, and all bleeding episodes were recorded. Children with or without bleeding were compared according to clinical, radiological, endoscopic, and biological parameters. In addition, validation of a predictive model for risk of variceal bleeding comprising of grade 2-3 esophageal varices, red spots, and fibrinogen level <150 mg/dL was applied on this cohort. RESULTS: Of 20 enrolled children, 6 had upper gastrointestinal bleeding. Significant differences were observed in fibrinogen level, adenosine diphosphate, and thrombin-dependent platelet aggregation. The model used to compute the upper gastrointestinal bleeding risk had an estimated predictive performance of 81.0%. Platelet aggregation analysis addition improved the estimated predictive performance up to 89.0%. CONCLUSIONS: We demonstrated an association between hemostatic factors and the upper gastrointestinal bleeding risk. A low fibrinogen level and platelet aggregation dysfunction may predict the risk of bleeding in children with decompensated cirrhosis. A predictive model is available to assess the upper gastrointestinal bleeding risk but needs further investigations. Clinicaltrials.gov number: NCT03244332.

Distal Aortic Arch Hypoplasia and Coarctation Repair: A Tailored Enlargement Technique.

BACKGROUND: Several techniques have been described to correct coarctation associated with distal arch hypoplasia. However, in neonates, residual gradients are frequently encountered and influence long-term outcome. We reviewed our experience with an alternative technique of repair combining carotid-subclavian angioplasty and extended end-to-end anastomosis. METHODS: From 1998 through 2014, 109 neonates (median age, 9 days) with coarctation and distal arch hypoplasia (n = 106) or type A interrupted aortic arch (n = 3) underwent repair using this technique. Thirty patients had isolated lesions (group 1), 44 associated ventricular septal defect (group 2), and 35 associated complex cardiac lesions (group 3). Median follow-up was 98 months. RESULTS: Repair was performed via left thoracotomy in 97%. There was one procedural-related death (0.9%) and overall five patients died during index admission (4.6%). Ten deaths were recorded at follow-up. Actuarial five-year survival was 86% (100% in group 1, 91% group 2, and 66% in group 3). Recurrent coarctation (clinical or invasive gradient >20 mm Hg) developed in 15 patients, all but 2 successfully treated by balloon dilatation. Freedom from any reintervention (dilatation or surgery) at five years was 86%. Only two patients were on antihypertensive drugs at last follow-up. CONCLUSIONS: This combined technique to correct distal arch hypoplasia and isthmic coarctation results in low mortality and acceptable recurrence rate. It preserves the left subclavian artery and allows enlargement of the distal arch diameter. Late outcome is excellent with very low prevalence of late arterial hypertension.

Aortic valve repair in the paediatric population: insights from a 38-year single-centre experience.

OBJECTIVES: To analyse our institutional results in the setting of paediatric aortic valve (AV) repair. Primary end-points were overall survival, freedom from AV reoperation and freedom from AV replacement. METHODS: A retrospective analysis of all patients under 18 years of age operated on from 1977 to 2015 in a single tertiary care level institution. Patients were included if they benefited from any type of AV repair procedure, including commissurotomy, leaflet shaving or plication, or leaflet augmentation. All data were gathered from patients' medical records, operative reports and referring paediatric cardiologists. The median follow-up was 50 months (IQR [13-140]). RESULTS: Sixty-six patients were included. Indications for surgery were aortic stenosis, aortic regurgitation and mixed disease in 13 (19%), 36 (55%) and 17 (26%) patients, respectively. According to El Khoury's functional classification, among the 55 patients with some degree of regurgitation there were 5 type Ib regurgitation, 23 type II and 27 type III. During AV repair, additional procedures were performed in 36 patients, VSD closure, subaortic membrane resection and mitral valve repair being the most frequent (18, 8 and 7 patients). RACHS score was predominantly 2 (98.5% of patients). The in-hospital mortality rate was 1.5% (1/66). Major morbidity included 10 pericardial effusions (1 pericardocentesis), 1 low cardiac output syndrome and 1 stroke. There were three late deaths (at 104, 140 and 179 months after repair). All were cardiac related. Overall 5- and 10-year survival rates were 100 and 95.7%. The rates of freedom from AV reoperation and AV replacement at 5 and 10 years were 90.6, 72.1 and 92.5, 82.7%, respectively. During follow-up, there was no occurrence of valve-related complication (endocarditis, thromboembolism and bleeding). CONCLUSIONS: In our experience, AV repair in the paediatric population provides excellent results in terms of both overall survival and valve-related reoperation. It obviates the need for chronic anticoagulation and in most cases delays the time at which more complex surgery such as the Ross procedure should be undertaken.

Does Postoperative Cardiac Troponin-I Have Any Prognostic Value in Predicting Midterm Mortality After Congenital Cardiac Surgery?

OBJECTIVES: This study evaluated the prognostic value of postoperative cardiac troponin-I (cTnI) in predicting all-cause mortality up to 3 months after normothermic congenital cardiac surgery. DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: All children ages 0 to 10 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: cTnI was measured after the induction of anesthesia but before the surgery, at the pediatric intensive care unit arrival, and at 4, 12, and 24 hours postoperatively. Follow-up was extended up to 6 months. Overall, 169 children were analyzed, of whom 165 were survivors and 4 were nonsurvivors. cTnI levels were significantly higher in nonsurvivors only at 24 hours (p = 0.047). Children undergoing surgery with cardiopulmonary bypass (CPB) had significantly higher cTnI concentrations compared with those without CPB (p<0.001). Logistic regression analysis was performed on the 146 children in the CPB group with the following predictive variables: CPB time, postoperative cTnI concentrations, the presence of a cyanotic malformation, and intramyocardial incision. None of the variables predicted mortality. Postoperative cTnI concentrations did not predict 6 months׳ mortality. Only cTnI at 24 hours predicted the length of stay in the pediatric intensive care unit. CONCLUSIONS: This study did not find that postoperative cTnI concentration predicted midterm mortality after normothermic congenital heart surgery. (ClinicalTrials.gov identifier: NCT01616394).

Unplanned intensive care unit admission after general anaesthesia in children: A single centre retrospective analysis.

OBJECTIVES: To determine the main causes for unplanned admission of children to the paediatric intensive care unit (PICU) following anaesthesia in our centre. To compare the results with previous publications and propose a data sheet for the prospective collection of such information. METHODS: Inclusion criteria were any patient under 16 years who had an unplanned post-anaesthetic admission to the PICU from 1999 to 2010 in our university hospital. Age, ASA score, type of procedure, origin and causes of the incident(s) that prompted admission and time of the admission decision were recorded. RESULTS: Out of a total of 44,559 paediatric interventions performed under anaesthesia during the study period, 85 were followed with an unplanned admission to the PICU: 67% of patients were younger than 5 years old. Their ASA status distribution from I to IV was 13, 47, 39 and 1%, respectively. The cause of admission was anaesthetic, surgical or mixed in 50, 37 and 13% of cases, respectively. The main causes of anaesthesia-related admission were respiratory or airway management problems (44%) and cardiac catheterisation complications (29%). In 62%, the admission decision was taken in the operating room. CONCLUSION: Unplanned admission to the PICU after general anaesthesia is a rare event. In our series, most cases were less than 5 years old and were associated with at least one comorbidity. The main cause of admission was respiratory distress and the main type of procedure associated with admission was cardiac catheterisation.

Feasibility Study on Neurally Adjusted Ventilatory Assist in Noninvasive Ventilation After Cardiac Surgery in Infants.

BACKGROUND: Our objective was to evaluate the feasibility, the quality of synchronization, and the influence on respiratory parameters of the noninvasive neurally adjusted ventilatory assist (NIV-NAVA) mode in infants after cardiac bypass surgery. We conducted a prospective, randomized cross-over study in infants undergoing noninvasive ventilation (NIV) after cardiac surgery. METHODS: Subjects were 10 infants < 5 kg. After extubation, subjects underwent 2 consecutive ventilatory modes after randomization into groups. In the CPAP first group, the subjects were ventilated first in nasal CPAP-1 and then in NIV-NAVA-2 for 30 min in each mode. In the NIV-NAVA first group, periods were reversed. All children were ventilated using the same interface. RESULTS: The analysis of curves showed a synchronization rate of 99.3% for all respiratory cycles. The rate of pneumatic inspiratory trigger was 3.4%. Asynchronies were infrequent. Some typical respiratory patterns (continuous effort and discontinuous inspiration) were found at rates of 10.9% and 31.1%, respectively. The respiratory trends showed a lower maximum diaphragmatic electrical activity (EAdi(max)) in NIV-NAVA periods compared with CPAP periods (P < .001 in the beginning of periods). The breathing frequency decreased significantly during the nasal CPAP-2 and NIV-NAVA-1 periods (P < .05). The inspiratory pressure increased significantly during the NIV-NAVA-1 and NIV-NAVA-2 periods (P < .05), but there was no significant difference for each parameter when comparing Δ values between the beginning and the end of each period. The EAdi signal was easy to obtain in all subjects, and no major side effects were associated with the use of NIV-NAVA. CONCLUSIONS: NIV-NAVA allows good synchronization in bi-level NIV in infant cardiac subjects weighing < 5 kg. The analysis of respiratory parameters shows that NIV NAVA decreases the work of breathing more effectively than nasal CPAP. The study shows some typical respiratory patterns in infants. (ClinicalTrials.gov registration NCT01570933.).

Living Donor Liver Transplantation in Children: Surgical and Immunological Results in 250 Recipients at Université Catholique de Louvain.

OBJECTIVES: To evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO compatibility, and impact of maternal donation on graft acceptance. BACKGROUND: LDLT and ABO-mismatched transplantation constitute feasible options to alleviate organ shortage in children. Vascular complications of portal hypoplasia in biliary atresia (BA) and acute rejection (AR) are still major concerns in this field. METHODS: Data from 250 pediatric LDLT recipients, performed at Cliniques Universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively. Results were analyzed according to ABO matching and PV complications. Uni- and multivariate analyses were performed to study the impact of immunosuppression, sex matching, and maternal donation on AR rate. RESULTS: Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft loss nor vascular rejection, nor hemolysis, was encountered in the ABO nonidentical patients (n = 58), provided pretransplant levels of relevant isoagglutinins were below 1/16. In BA recipients, the rate of PV complications was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and to jump graft interposition (26.9%; P = 0.027). In parental donation, maternal grafts were associated with higher 1-year AR-free survival (55.2%) than paternal grafts (39.8%; P = 0.041), but only in BA patients. CONCLUSIONS: LDLT, including ABO-mismatched transplantation, constitutes a safe and efficient therapy for liver failure in children. In BA patients with PV hypoplasia, portoplasty seems to constitute the best technique for PV reconstruction. Maternal donation might be a protective factor for AR.

Off-pump revascularization in a 2-year-old girl after neonatal arterial switch.

One drawback of the arterial switch operation for treating transposition of the great arteries is the occurrence of coronary lesions, found during follow-up in about 5% of (a)symptomatic children. The established corrective procedures include coronary artery proximal patch arterioplasty or coronary artery bypass grafting (CABG). To avoid aortic manipulations and extracorporeal circulation, off-pump coronary artery bypass (OPCAB) has become increasingly used in the adult population. We report a case of OPCAB revascularization in a symptomatic 2-year-old child.

Cardiac and neurological assessment of normothermia/warm blood cardioplegia vs hypothermia/cold crystalloid cardioplegia in pediatric cardiac surgery: insight from a prospective randomized trial.

OBJECTIVE: Although normothermia and warm blood cardioplegia are widely used in adults, cold crystalloids and hypothermia remain routinely used in pediatric cardiac surgery. The superiority of either technique in both brain and myocardial protection remains controversial. We designed a prospective randomized study to compare both approaches in terms of early myocardial protection and late neurodevelopmental status. METHODS: From 2004 to 2005, 47 patients were randomly assigned to either mild hypothermia associated to cold crystalloid cardioplegia (CCC, 22 patients) or normothermia with intermittent warm blood cardioplegia (IWBC, 25 patients). Intramyocyte adenosine triphosphate (ATP) was measured before, during and after cardioplegic arrest and results between groups were compared. In addition to their cardiac status, early and late neurologic assessment was performed by psychometric evaluation tests. RESULTS: Intracellular ATP levels were not significantly different between the two groups. However, intragroup comparison revealed different profiles according to myocardial protection: in the normothermia/warm blood cardioplegia group, ATP concentration increased during cardioplegic arrest and returned to initial values afterward (11 nmol mg(-1) vs 21 nmol mg(-1) vs 10 nmol mg(-1), p < 0.001), such changes did not occur in the cold protocol (17 nmol mg(-1) vs 19 nmol mg(-1) vs 14 nmol mg(-1), p = NS). Early neurological outcome was similar in both groups. At late follow-up (mean = 4 years), no significant difference was observed between the two groups. CONCLUSIONS: This study demonstrates that normothermia/IWBC protocols are not deleterious when compared with more conventional approaches. A more physiologic ATP steady state, reflecting the absence of cellular ischemic insult was observed in the IWBC group. Importantly, no significant difference was found between IWBC and CCC groups in terms of early and late neurodevelopmental status.

Levosimendan in congenital cardiac surgery: a randomized, double-blind clinical trial.

OBJECTIVE: In this study, the authors used a continuous infusion of either levosimendan or milrinone as inotropic support after corrective congenital cardiac surgery. The hemodynamic and biochemical parameters were compared. DESIGN: A prospective, randomized, double-blind clinical study. SETTING: A university hospital. PARTICIPANTS: Forty-one patients between 0 and 5 years old requiring inotropic support for corrective congenital heart surgery under cardiopulmonary bypass (CPB) were enrolled in this trial. Thirty-six patients completed the study. INTERVENTIONS: Patients were randomized in a double-blind fashion to a continuous infusion of either levosimendan at 0.05 µg/kg/min or milrinone at 0.4 µg/kg/min started at the onset of CPB. Epinephrine was started at 0.02 µg/kg/min after aortic cross-clamp release in both groups. MEASUREMENTS AND MAIN RESULTS: There was no significant difference between serum lactate levels of groups. The rate-pressure index (the product of heart rate and systolic blood pressure), which is an indicator of myocardial oxygen demand, was significantly lower at 24 hours and 48 hours postoperatively in the levosimendan group (p < 0.001) in comparison to the milrinone group. Although not significantly different, the troponin values in the levosimendan group were less at 1 hour (median [P(25)-P(75)]: 20.7 [15.3- 48.3] v 34.6 [23.8- 64.5] ng/mL and 4 hours postoperatively: 30.4 [17.3-59.9] v 33.3 [25.5-76.7] ng/mL). CONCLUSION: Levosimendan is at least as efficacious as milrinone after corrective congenital cardiac surgery in neonates and infants.

Vascular access in the neonate.

Up to recently, inserting venous or arterial 'lines' in the neonate was essentially based on clinical skill and experience. The recent advent of portable ultrasound (US) machines with paediatric probes has resulted in the development of new approaches that, if correctly learned and used, should allow quicker and safer vascular access in this population. Both classic and new techniques are reviewed on the basis of literature and authors' experience.

Liver transplantation in children with fulminant hepatic failure: The UCL experience.

The outcome of pediatric LT for FHF was shown to be poor in our center. To better understand such results, recipient and transplant parameters with a putative impact on post-transplant outcome were analyzed in LT for FHF. Between March 1984 and June 2002, 33 children with FHF received a primary liver allograft. The overall results in this series were studied with respect to pre-operative demographic and metabolic variables, peri-operative events, and outcome. Five-yr patient and graft survivals were 71% and 66%, respectively, with a retransplantation rate at 18%. Incidences of perioperative hemorrhage, of HAT and PVT were 14%, 8%, and 4%, respectively. Five-yr acute rejection-free survival rate was 55%. These data confirm the worse outcome following LT for FHF when compared with LT in elective, non-malignant indications such as BA; results in FHF could not be related to surgical or immunological complications in the post-transplant period and it is hypothesized that the MOF associated with FHF contributes to early post-transplant mortality which would justify special management, including aggressive renal and hepatic support.

Fomepizole alone for severe infant ethylene glycol poisoning.

OBJECTIVE: To report a case of a massive ingestion of ethylene glycol in an infant successfully treated by fomepizole without hemodialysis. DESIGN: Descriptive case report. SETTING: Pediatric intensive care unit. PATIENT: A 5-mo-old boy who ingested 200 mL of an antifreeze solution. INTERVENTIONS: Antidotal therapy with a total of seven doses of fomepizole administered intravenously with an interval of 12 hrs (15 mg/kg as loading dose, then 10 mg/kg). Hemodialysis was not performed. MEASUREMENTS AND MAIN RESULTS: Iterative determination of ethylene glycol concentration was obtained in blood and urine. Kinetics were calculated for ethylene glycol and fomepizole elimination. The infant made a complete recovery with no change in renal function. CONCLUSIONS: Although not yet approved for this indication in the child, fomepizole seemed safe and effective in a case of severe ethylene glycol poisoning, without the need for hemodialysis.