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Objective: The objective of this study was to evaluate the association between the minimal count of lymphocyte (Ly&#95;Min) after cardiac surgery with cardiopulmonary bypass and the occurrence of infections within the first 30 postoperative days (POD)., Methods: From a local European Congenital Heart Surgeons Association (ECHSA) database, all cardiac surgeries with cardiopulmonary bypass in children under 18 years old between January 2014 and December 2021 were eligible. Infections occurring within 30 POD were prospectively recorded according to ECHSA definitions, and classified into sepsis, pneumonia, wound infection, mediastinitis or endocarditis. For each surgery, Ly&#95;Min was collected during the first 2 POD and the optimal threshold for predicting infection was chosen using receiver operating characteristic curve analysis. Univariate and multivariate logistic regression analyses were performed to identify variables associated with the risk of infection., Results: Of 1428 surgeries conducted over the 8-year period, 111 (8%) were complicated by at least 1 infection, including pneumonia (n = 45), wound infection (n = 41), sepsis (n = 24), mediastinitis (n = 20) and endocarditis (n = 3). Mean Ly&#95;Min in the first 2 POD was lower in the infected group compared with the noninfected group (1.32 ± 0.81 vs. 1.81 ± 1.05 × 109/L, P < 0.001). After adjusting for confounders, Ly&#95;Min <1.105 × 109/L within the first 1 POD was independently associated with an increased risk of postoperative infections (adjusted odds ratio = 1.75, 95% confidence interval: 1.10-2.79, P = 0.019)., Conclusions: In this large single-center cohort of pediatric cardiac surgeries, Ly&#95;Min during the first 2 POD was associated with the development of infections within 30 days after cardiopulmonary bypass., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Sickle cell disease (SCD) is a global hemoglobinopathy; approximately 300 000 individuals are diagnosed annually. Acute chest syndrome (ACS), a common complication, leads to significant hospitalization and mortality, particularly in cases of severe respiratory distress. ECMO outcomes in this specific population are poorly described., Methods: This retrospective observational study, utilizing data from the Extracorporeal Life Support Organization (ELSO) registry, focuses on children and young adults (<40 years) with SCD undergoing ECMO from 1998 to 2022., Results: We observed a growing trend in ECMO cases over the last 15 years, with 210 SCD patients identified in the registry (five neonates, 95 children, 110 adults). ECMO was predominantly initiated for pulmonary support (62%), and most of the primary diagnoses were related to SCD (reported as "SCD" or "acute chest syndrome"). The global survival rate was 55.8% (59% for children and 52.7% for adults). None of the children supported for extracorporeal cardiopulmonary resuscitation survived, and only 2/18 (11%) of adults cannulated for ECPR survived. Complication rates, including acute renal failure (33.8%) neurological events (13%), thrombotic (23.3%), or bleeding events (22.9%) were not noticeably different from reported outcomes in the ELSO registry., Conclusion: Our findings suggest that ECMO outcomes in SCD patients align with general ECMO trends and may not be limited by suspected unfavorable results in children and young adults. Despite limitations, our study contributes valuable insights into using ECMO in SCD, emphasizing the need for further research and understanding in this underexplored domain., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Purpose: Toxic shock syndrome (TSS) is a rare disease responsible for significant morbidity and mortality. Intravenous immunoglobulin (IG) therapy in paediatric TSS could improve shock and organ failure, but more consistent efficacy and safety data are needed. Our objective was to determine whether a randomised clinical trial (RCT) assessing intravenous IG in TSS in children is feasible., Methods: We performed a multicentre, feasibility, double-blind RCT assessing efficacy of high-dose intravenous IG versus albumin 4% (control group) within the first 12 hours of shock onset. Included patients were aged above 1 month and below 18 years with suspected TSS and septic shock. Feasibility was assessed by measuring inclusion rate, protocol compliance and missing data regarding death and the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score. Other secondary clinical outcomes were evaluated during hospital stay, at 60 day and 1 year., Results: 28 patients, admitted in 6 paediatric intensive care units during 36 consecutive months and followed for 1 year, received the allocated treatment: 13 in intravenous IG group, 15 in control group. The median age was 10.6 years and the sex ratio was 1. Inclusion rate was above 50%, protocol deviations were below 30% and missing data regarding death and PELOD-2 Score below 10%. No difference concerning secondary clinical outcomes between groups was observed, and more adverse events were reported in the control group., Conclusion: It seems to be feasible to conduct an RCT assessing intravenous IG efficacy and safety in paediatric TSS but must be realised internationally, with choice of a clinically relevant endpoint and a specific design in order to be realistic., Trial Registration Number: NCT02219165., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Extracorporeal life support can lead to rapid reversal of hypoxemia but the benefits and harms of different oxygenation targets in severely ill patients are unclear. Our primary objective was to investigate the association between the Pa o2 after extracorporeal membrane oxygenation (ECMO) initiation and mortality in neonates treated for respiratory failure., Design: Retrospective analysis of the Extracorporeal Life Support Organization (ELSO) Registry data, 2015-2020., Patients: Newborns supported by ECMO for respiratory indication were included., Interventions: None., Measurements and Main Results: Pa o2 24 hours after ECMO initiation (H24 Pa o2 ) was reported. The primary outcome was 28-day mortality. We identified 3533 newborns (median age 1 d [interquartile range (IQR), 1-3]; median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers, who were placed on ECMO. By 28 days of life, 731 (20.7%) had died. The median H24 Pa o2 was 85 mm Hg (IQR, 60-142). We found that both hypoxia (Pa o2 < 60 mm Hg) and moderate hyperoxia (Pa o2 201-300 mm Hg) were associated with greater adjusted odds ratio (aOR [95% CI]) of 28-day mortality, respectively: aOR 1.44 (95% CI, 1.08-1.93), p = 0.016, and aOR 1.49 (95% CI, 1.01-2.19), p value equals to 0.045., Conclusions: Early hypoxia or moderate hyperoxia after ECMO initiation are each associated with greater odds of 28-day mortality among neonates requiring ECMO for respiratory failure., Competing Interests: Dr. Tonna is supported by a Career Development Award from the National Institutes of Health/National Heart, Lung, and Blood Institute (K23 HL141596). Dr. Tonna is the Chair of the Registry Committee of the Extracorporeal Life Support Organization. Dr. Moscatelli is a consultant for Air Liquide Santé International as a member of the advisory board on the use of inhaled nitric oxide for cardiothoracic indications. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

To evaluate the feasibility of continuous determination of the optimal mean arterial blood pressure (opt-MAP) according to cerebral autoregulation and to describe the opt-MAP, the autoregulation limits, and the time spent outside these limits in children within 48 h of cardiac surgery. Cerebral autoregulation was assessed using the correlation coefficient (COx) between cerebral oxygenation and MAP in children following cardiac surgery. Plots depicting the COx according to the MAP were used to determine the opt-MAP using weighted multiple time windows. For each patient, we estimated (1) the time spent with MAP outside the autoregulation limits and (2) the burden of deviation, defined as the area between the MAP curve and the autoregulation limits when the MAP was outside these limits. Fifty-one patients with a median age of 7.1 (IQR 0.7-52.0) months old were included. The opt-MAP was calculated for 94% (IQR 90-96) of the monitored time. The opt-MAP was significantly lower in neonates < 1 month old. The patients spent 24% (18-31) of the time outside of the autoregulation limits, with no significant differences between age groups. Continuous determination of the opt-MAP is feasible in children within the first 48 h following cardiac surgery., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Carboxyhemoglobin (COHb) is potentially a novel marker of hemolysis on extracorporeal membrane oxygenation (ECMO) and may be useful as an indicator for circuit-related complication in adults, but little is known about COHb levels in children. An observational single-center study was performed between January 2018 and December 2021. Fifty-eight children were included and COHb levels were obtained along with routine blood gas analysis before, during, and after ECMO support. From the 6th hour of ECMO support, the COHb level increased relative to the pre-ECMO level, with an adjusted mean difference of 0.44 (95% confidence interval [CI], 0.26-0.62; p < 0.001) and remained higher during ECMO run and within 6 hours after weaning ( p < 0.001). Among the 18 children (31%) who experienced at least one circuit-related complication leading to a circuit change, we observed a significant decrease in COHb levels within 24 hours after the circuit change, compared with the 24 hours before (adjusted mean difference, 0.54%; 95% CI, 0.27-0.80; p < 0.001). The maximal daily COHb level was able to predict circuit-related complications within 24 hours following COHb measurement with an area under the receiver operating characteristic (ROC) curve of 0.85 (95% CI, 0.77-0.92; p < 0.001)., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Purpose: Early prognostication of neurologic outcome in neonates and children supported with extra-corporeal membrane oxygenation (ECMO) is challenging. Amplitude-integrated EEG (aEEG) offers the advantages of continuous monitoring and 24-hours availability at the bedside for intensive care unit providers. The objective of this study was to describe the early electrophysiological background patterns of neonates and children undergoing ECMO and their association with neurologic outcomes., Methods: This was a retrospective review of neonates and children undergoing ECMO and monitored with aEEG. Amplitude-integrated EEG was summarized as an aEEG background score determined within the first 24 hours of ECMO and divided in 3-hour periods. Screening for electrical seizures was performed throughout the full ECMO duration. Neurologic outcome was defined by the Pediatric Cerebral Performance Category score at hospital discharge., Results: Seventy-three patients (median age 79 days [8-660], median weight 4.78 kg [3.24-10.02]) were included in the analysis. Thirty-two patients had a favorable neurologic outcome and 41 had an unfavorable neurologic outcome group at hospital discharge. A 24-hour aEEG background score >17 was associated with an unfavorable outcome with a sensitivity of 44%, a specificity of 97%, a positive predictive value of 95%, and a negative predictive value of 57%. In multivariate analysis, 24-hour aEEG background score was associated with unfavorable outcome (hazard ratio, 6.1; p = 0.001; 95% confidence interval, 2.31-16.24). The presence of seizures was not associated with neurologic outcome at hospital discharge., Conclusions: Continuous aEEG provides accurate neurologic prognostication in neonates and children supported with ECMO. Early aEEG monitoring may help intensive care unit providers to guide clinical care and family counseling., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Objectives: The antiarrhythmic effects of dexmedetomidine (DEX) have been suggested, but there are controversial reports on the effectiveness of intraoperative use of DEX to reduce the incidence of postoperative tachyarrhythmia (POT)., Methods: From a local European Congenital Heart Surgery Association database, we included patients operated for congenital heart diseases under cardiopulmonary bypass within a 5-year period (2017-2021), during which intraoperative use of high dose of DEX (1-1.4 µg/kg/h) was implemented. A doubly robust matching estimation of the causal effect of DEX on the incidence of POT was conducted. We combined a multimodal estimation model in patients not exposed to DEX (disease risk score) as well as a regression analysis in a matched cohort for patients exposured to DEX., Results: From a cohort of 593 surgeries (514 patients) occurring during the study period, doubly matched analysis consisted of the analysis of 426 surgeries conducted under DEX or not (213 per group). The probability of developing POT in patients exposed to DEX was 6.6% (95% confidence interval 0.032-0.099) vs 14.5% (95% confidence interval 0.098-0.193) in the group of patients not exposed to DEX. The doubly robust matched estimation method showed a mean reduction of 8.8% (95% confidence interval -0.137 to -0.023) of POT when DEX is used for intraoperative anaesthesia., Conclusions: The use of high doses of DEX during anaesthesia for congenital heart surgery in neonates and infants is associated with a moderate but significant reduction of POT., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The primary objective was to investigate the association between partial pressure of carbon dioxide (PaCO 2 ) change after extracorporeal membrane oxygenation (ECMO) initiation and neurologic outcome in neonates treated for respiratory failure. A retrospective analysis of the Extracorporeal Life Support Organization (ELSO) database including newborns supported by ECMO for respiratory indication during 2015-2020. The closest Pre-ECMO (Pre-ECMO PaCO 2 ) and at 24 hours after ECMO initiation (H24 PaCO 2 ) PaCO 2 values allowed to calculate the relative change in PaCO 2 (Rel Δ PaCO 2 = [H24 PaCO 2 - Pre-ECMO PaCO 2 ]/Pre-ECMO PaCO 2 ). The primary outcome was the onset of any acute neurologic event (ANE), defined as cerebral bleeding, ischemic stroke, clinical or electrical seizure, or brain death during ECMO. We included 3,583 newborns (median age 1 day [interquartile range {IQR}, 1-3], median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers. The median Rel Δ PaCO 2 value was -29.9% [IQR, -46.2 to -8.5]. Six hundred nine (17%) of them had ANE (405 cerebral bleedings, 111 ischemic strokes, 225 seizures, and 6 brain deaths). Patients with a decrease of PaCO 2 > 50% were more likely to develop ANE than others (odds ratio [OR] 1.78, 95% confidence interval [CI], 1.31-2.42, p < 0.001). This was still observed after adjustment for all clinically relevant confounding factors (adjusted OR 1.94, 95% CI, 1.29-2.92, p = 0.001). A significant decrease in PaCO 2 after ECMO start is associated with ANE among neonates requiring ECMO for respiratory failure. Cautious PaCO 2 decrease should be considered after start of ECMO therapy., Competing Interests: J.E.T. is supported by a Career Development Award from the National Institutes of Health/National Heart, Lung, And Blood Institute (K23 HL141596). J.E.T. received speaker fees and travel compensation from LivaNova and Philips Healthcare, unrelated to this work. All other authors declare no conflict of interest., (Copyright © ASAIO 2022.)

Background: Levosimendan (LVSMD) is a calcium-sensitizer inotropic and vasodilator agent whose use might have a beneficial effect on the weaning of venoarterial extracorporeal membrane oxygenation (VA-ECMO). In light of LVSMD pharmacological characteristics, we hypothesized that ECMO may induce major pharmacokinetic (PK) modifications for LVSMD and its metabolites., Objective: The aim of this study was to investigate the PK of LVSMD and its metabolites, and to assess the effects of ECMO on PK parameters., Methods: We conducted a multicentric, prospective study (NCT03681379). Twenty-seven infusions of LVSMD were performed, allowing for the collection of 255 blood samples. Non-linear mixed-effects modeling software (MONOLIX®) was used to develop a parent-metabolite PK model of LVSMD and its metabolites., Results: Most patients received a 0.2 µg/kg/min infusion of LVSMD over 24 h. After elimination of non-reliable samples or concentrations below the limit of quantification, 166, 101 and 85 samples were considered for LVSMD, OR-1855 and OR-1896, respectively, of which 81, 53 and 41, respectively, were drawn under ECMO conditions. Parent-metabolite PK modeling revealed that a two-compartment model with first-order elimination best described LVSMD PK. Use of a transit compartment allowed for an explanation of the delayed appearance of circulating OR-1855 and OR-1896, with the latter following a first-order elimination. Patient weight influenced the central volume of distribution and elimination of LVSMD. ECMO support increased the elimination rate of LVSMD by 78%, and ECMO also slowed down the metabolite formation rate by 85% for OR-1855, which in turn is converted to the active metabolite OR-1896, 14% slower than without ECMO. Simulated data revealed that standard dosing may not be appropriate for patients under ECMO, with a decrease in the steady-state concentration of LVSMD and lower exposure to the active metabolite OR-1896., Conclusions: ECMO altered PK parameters for LVSMD and its metabolites. An infusion of LVSMD over 48 h, instead of 24 h, with a slightly higher dose may promote synthesis of the active metabolite OR-1896, which is responsible for the long-term efficacy of LVSMD. Further trials evaluating ECMO effects using a PK/pharmacodynamic approach may be of interest., Registration: ClinicalTrials.gov identifier number NCT03681379., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: To review use of semiautomated regional citrate anticoagulation (saRCA) for continuous kidney replacement therapy (CKRT) in young children., Design: Retrospective cohort study., Setting: Three independent PICUs., Patients: All consecutive children weighing less than 11 kg who received CKRT with saRCA from January 2015 to June 2020., Interventions: None., Measurements and Main Results: Twenty-one children weighing less than 11 kg underwent CKRT with saRCA. The total duration of the CKRT was 2,014 hours, with a total of 64 CKRT sessions. Citrate intoxication occurred in four of 64 CKRT sessions (6%). Citrate intoxication was consistently observed in the few CKRT sessions where the initial lactate concentration was greater than 4 mmol/L or the ratio of replacement fluid flow to citrate flow less than 50%. The rate of unscheduled interruptions of CKRT sessions was 25% (16/64)., Conclusions: We have used saRCA for CKRT in children weighing less than 11 kg. A strict protocol and intensive training are required to minimize complications., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

The impact of cervical cannulation on neurologic outcome has not been yet studied among children receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) in the context of severe sepsis or septic shock. A retrospective cohort study was performed using the extracorporeal life support organization (ELSO) registry. A total of 559 children weighing less than 20 kg with a primary or secondary diagnosis of severe sepsis, septic shock or toxic shock syndrome were included between January 1, 2010, and December 31, 2019. Cervical cannulation was performed in 485 children (87%) and central cannulation in 74 children (13%). The prevalence of acute neurologic event (ANE) was 32%, including clinical and/or electroencephalographic seizures, cerebral infarction, cerebral hemorrhage, and/or brain death. In multivariable analysis, we did not find an association between cervical cannulation and greater/lesser odds of ANE during ECMO (adjusted odds ratio [aOR] = 1.39, 95% confidence interval [CI] 0.72-2.65; P = 0.326). Only pre-ECMO acidosis was independently associated with the development of ANE (pH < 6.99; aOR = 2.71, 95% CI 1.34-5.49; P = 0.006; pH 6.99 to <7.12; aOR = 2.57, 95% CI 1.37-4.82; P = 0.003). Thus, the site of cannulation appears not as a modifiable neurologic risk factor in this young septic population., Competing Interests: Disclosure: P.R. is a member of the ELSO Executive Committee and J.T. is a member of the ELSO Registry committee. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Objectives: To describe the frequency and outcomes on the use of extracorporeal membrane oxygenation (ECMO) among critically ill neonates and children within a structured pediatric critical care network in the West of France. To assess the optimality of decision-making process for patients primarily admitted in non-ECMO centers., Design: Observational prospective population-based study from January 2015 to December 2019., Patients: Neonates over 34 weeks of gestational age, weighing more than 2,000 g and children under 15 years and 3 months old admitted in one of the 10 units belonging to a Regional Pediatric Critical Care Network., Interventions: None., Measurements and Main Results: Eight-thousand one hundred eighty-nine children and 3,947 newborns were admitted within one of the 10 units of the network over the study period. Sixty-five children (8.1% [95% CI, 6.2-10‰]) and 35 newborns (9.4% [95% CI, 6.4-12%]) required ECMO support. Of these patients, 31 were first admitted to a non-ECMO center, where 20 were cannulated in situ (outside the regional ECMO center) and 11 after transfer to the ECMO regional center. Cardiogenic shock, highest serum lactate level, and cardiac arrest prior to first phone call with the regional ECMO center were associated with higher rate of in situ cannulation. During the study period, most of the patients were cannulated for underlying cardiac issue (42/100), postoperative cardiac surgery instability (38/100), and pediatric (10/100) and neonatal (10/100) respiratory distress syndrome. Patients primarily admitted in non-ECMO centers or not had similar 28-day post-ICU survival rates compared with those admitted in the referral ECMO center (58% vs 51%; p = 0.332). Pre-ECMO cardiac arrest, ECMO, and lower pH at ECMO onset were associated with lower 28-day post-ICU survival., Conclusions: Our local results suggest that a structured referral network for neonatal and pediatric ECMO in the region of Western France facilitated escalation of care with noninferior (or similar) early mortality outcome. Our data support establishing referral networks in other equivalent regions., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Diaphragmatic paralysis following congenital cardiac surgery is associated with significant morbidity and mortality. Spontaneous recovery of diaphragmatic function has been described, contrasting with centres providing early diaphragmatic plication. We aimed to describe the outcomes of a conservative approach, as well as to identify factors associated with a failure of the strategy., Methods: This is a retrospective study of patients admitted after cardiac surgery and suffering unilateral diaphragmatic paralysis within 2 French Paediatric Cardiac Surgery Centers. The conservative approach, defined by the prolonged use of ventilation until successful weaning from respiratory support, was the primary strategy adopted in both centres. In case of unsuccessful evolution, a diaphragmatic plication was scheduled. Total ventilation time included invasive and non-invasive ventilation. Diaphragm asymmetry was defined by the number of posterior rib segments counted between the 2 hemi-diaphragms on the chest X-ray after cardiac surgery., Results: Fifty-one neonates and infants were included in the analysis. Patients' median age was 12.0 days at cardiac surgery (5.0-82.0), and median weight was 3.5 kg (2.8-4.9). The conservative approach was successful for 32/51 patients (63%), whereas 19/51 patients (37%) needed diaphragm plication. There was no difference in patients' characteristics between groups. Respiratory support prolonged for 21 days or more and diaphragm asymmetry more than 2 rib segments were independently associated with the failure of the conservative strategy [odds ratio (OR) 6.9 (1.29-37.3); P = 0.024 and OR 6.0 (1.4-24.7); P = 0.013, respectively]., Conclusions: The conservative approach was successful for 63% of the patients. We identified risk factors associated with the strategy's failure., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Cerebral autoregulation (CA) impairment is associated with neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Severe variations of arterial CO 2 (PaCO 2 ) and O 2 (PaO 2 ) tension after ECMO onset are common and associate with mortality and poor neurological outcome. The impact of gas exchange on CA among critically ill patients is poorly studied., Methods: Retrospective analysis of data collected prospectively from 30 children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France. A correlation coefficient between the variations of regional cerebral oxygen saturation (rSO 2 ) and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). Cox-MAP plots were investigated allowing determining lower limit of autoregulation (LLA) and upper limit of autoregulation (ULA) limits of autoregulation. Age-based normal blood pressure was used to adjust the MAP, LLA, and ULA data from each patient and then reported as percentage (nMAP, nLLA, and nULA, respectively). RSO 2 , COx, nMAP, nLLA, and nULA values were averaged over one hour before each arterial blood gas (ABG) sample during ECMO run., Results: Thirty children (median age 4.8 months [Interquartile range (IQR) 0.7-39.1], median weight 5 kg [IQR 4-15]) experiencing 31 ECMO runs were included in the study. Three hundred and ninety ABGs were analyzed. The highest values of COx were observed on day 1 (D1) of ECMO. The relationship between COx and PaCO 2 was nonlinear, but COx values tended to be lower in case of hypercapnia compared to normocapnia. During the whole ECMO run, a weak but significant correlation between PaCO 2 and nULA was observed (R = 0.432, p = 0.02). On D1 of ECMO, this correlation was stronger (R = 0.85, p = 0.03) and a positive correlation between nLLA and PaCO 2 was also found (R = 0.726, p < 0.001). A very weak negative correlation between PaO 2 and nULA was observed within the whole ECMO run and on D1 of ECMO (R =  -0.07 p = 0.04 and R =  -0.135 p =  <0.001, respectively). The difference between nULA and nLLA representing the span of the autoregulation plateau was positively correlated with PaCO 2 and negatively correlated with PaO 2 (R = 0.224, p = 0.01 and R =  -0.051, p = 0.004, respectively)., Conclusions: We observed a complex relationship between PaCO 2 and CA, influenced by the level of blood pressure. Hypercapnia seems to be globally protective in normotensive or hypertensive condition, while, in case of very low MAP, hypercapnia may disturb CA as it increases LLA. These data add additional arguments for very cautiously lower PaCO 2 , especially after ECMO start., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: Cerebral autoregulation (CA) impairment may pose a risk factor for neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Our first objective was to investigate the feasibility of CA continuous monitoring during ECMO treatment and to describe its evolution over time. The second objective was to analyze the association between CA impairment and neurological outcome., Design: Observational prospective study., Patients and Setting: Twenty-nine children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France, and the PICU of the IRCCS Giannina Gaslini Institute in Genoa, Italy., Measurements: A correlation coefficient between the variations of regional cerebral oxygen saturation and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). A COx > 0.3 was considered as indicative of autoregulation impairment. COx-MAP plots were investigated allowing determining optimal MAP (MAPopt) and limits of autoregulation: lower (LLA) and upper (ULA). Neurological outcome was assessed by the onset of an acute neurological event (ANE) after ECMO start., Results: We included 29 children (median age 84 days, weight 4.8 kg). MAPopt, LLA, and ULA were detected in 90.8% (84.3-93.3) of monitoring time. Mean COx was significantly higher during day 1 of ECMO compared to day 2 [0.1 (0.02-0.15) vs. 0.01 (- 0.05 to 0.1), p = 0.002]. Twelve children experienced ANE (34.5%). The mean COx and the percentage of time spent with a COx > 0.3 were significantly higher among ANE+ compared to ANE- patients [0.09 (0.01-0.23) vs. 0.04 (- 0.02 to 0.06), p = 0.04 and 33.3% (24.8-62.1) vs. 20.8% (17.3-23.7) p = 0.001]. ANE+ patients spent significantly more time with MAP below LLA [17.2% (6.5-32.9) vs. 5.6% (3.6-9.9), p = 0.02] and above ULA [13% (5.3-38.4) vs. 4.2% (2.7-7.4), p = 0.004], respectively., Conclusion: CA assessment is feasible in pediatric ECMO. The first 24 h following ECMO represents the most critical period regarding CA. Impaired autoregulation is significantly more severe among patients who experience ANE.

Background: Monocytic human leukocyte antigen DR (mHLA-DR) expression levels have been reported to be a marker of immunosuppression and a predictor of sepsis and mortality. There are, however, scant data regarding mHLA-DR monitoring in young infants after cardiopulmonary bypass. Our objectives were to investigate the kinetics of mHLA-DR expression and to determine whether mHLA-DR levels are associated with healthcare-associated infection (HAI) after cardiopulmonary bypass in young infants., Methods: mHLA-DR levels were analyzed by flow cytometry using a standardized method in 49 infants (<3 months old) with congenital heart disease before and after cardiopulmonary bypass. Results are expressed as the number of anti-HLA-DR antibodies per cell (AB/c)., Results: Postoperative mHLA-DR expression was reduced in all infants. Eleven patients (22%) developed HAI, and 4 patients (8%) died during the 30-day follow-up. mHLA-DR expression was significantly lower on postoperative day 4 in the HAI group compared with those who without HAI (3768 AB/c [range, 1938-6144] vs 13,230 AB/c [range, 6152-19,130], P = .014). Although mHLA-DR expression was associated with postoperative severity, mHLA-DR ≤4500 AB/c in the first 72 hours among patients with higher postoperative severity (extracorporeal membrane oxygenation and/or corticoids and/or delayed closure of sternum) was associated with occurrence of HAI in the univariate analysis (odds ratio, 6.3; 95% confidence interval, 1.0-38.7; P = .037)., Conclusions: Cardiopulmonary bypass induces a profound decrease in mHLA-DR expression in young infants. Among patients with higher postoperative severity, low level of mHLA-DR in the early postoperative period is associated with the development of HAI., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Children supported by extracorporeal membrane oxygenation present a high risk of neurological complications. Although carotid cannulation is known to be associated with neurologic injury, conflicting data exist with regard to the predominance of right- or left-sided lesions. We describe here two infants requiring veno-arterial extracorporeal membrane oxygenation for septic shock who encountered right watershed infarction ipsilateral to carotid artery cannulation. Hemodynamic failure seems to be the most probable underlying mechanism. The asymmetry of transcranial Doppler metrics in one case and the low right regional cerebral oxygen saturation value observed soon after right cannulation in both cases suggest an insufficient cerebral collateral flow compensation. The risk of ipsilateral watershed injury should be considered before cervical cannulation, notably in the context of sepsis and an evaluation of the cerebral collateral blood flow before and just after cannulation may be interesting in order to identify infants with higher risk of ipsilateral ischemic lesions.

Competing Interests: Authors have no conflict of interest to disclose.

Purposes: Amplitude-integrated EEG (aEEG) has been widely developed in neonatal intensive care unit, but few studies focused on pediatric intensive care unit. Furthermore, reliability of aEEG under real-life conditions is unknown., Methods: Participants were nurses from a 12-bed pediatric intensive care unit in a referral university hospital in France. Amplitude EEG was implemented after standardized training, including e-learning course, individual feedback and bedside teaching concerning monitoring installation, background classification patterns recognition, artefact analysis, and seizure detection. The primary judgment criterion was the agreement (Cohen Kappa) between nurses and aEEG experts for the detection of abnormal aEEG traces (moderately or severely altered background pattern according to Hellström-Westas classification and/or seizure activity)., Results: During the study period, 196 consecutives traces from 79 patients were analyzed by 51 nurses. According to expert's classification, 53% of traces were abnormal, including 17.5% of severely abnormal traces (severely altered traces and/or seizure activity) and 14% exhibiting seizure activity. Moderate agreement between experts and nurses was found for detection of any abnormal trace (k = 0.53; 95% confidence interval [CI]: 0.39-0.67). Substantial agreement was found for severely altered traces (k = 0.71; 95% CI: 0.57-0.85). Finally, fair agreement was found for seizure detection (irrespective of background classification, k = 0.40; 95% CI: 0.25-0.54)., Conclusions: These results suggest that aEEG monitoring may be implemented in routine nursing care in pediatric intensive care unit. Further training courses are needed to enhance nurses' skill in detecting seizures activity at the bedside.

Objectives: To assess the ability of amplitude-integrated electroencephalography monitoring within 24 hours of the return of spontaneous circulation to prognosticate neurologic outcomes in children following cardiac arrest DESIGN:: Retrospective review of prospectively recorded data. An amplitude-integrated electroencephalography background score was calculated according to background activity during the first 24 hours after return of spontaneous circulation, a higher score correlating with more impaired background activity. The primary endpoint was the neurologic outcome as defined by the Pediatric Cerebral Performance Category at PICU discharge (Pediatric Cerebral Performance Category 1-3: a good neurologic outcome; Pediatric Cerebral Performance Category 4-6: a poor neurologic outcome)., Setting: A referral PICU., Patients: Thirty children with a median age of 10 months (2-38 mo) and a male/female sex ratio of 1.3 were included., Interventions: None., Measurements and Main Results: Eighteen patients were assigned to the favorable outcome group and 12 to the unfavorable outcome group. The median time between return of spontaneous circulation and amplitude-integrated electroencephalography initiation was 4 hours (3-9 hr). The amplitude-integrated electroencephalography score within 24 hours after return of spontaneous circulation was significantly higher in the children with poor outcomes compared with those with good outcomes (12 ± 4 vs 25 ± 8; p < 0.001). Background activity during amplitude-integrated electroencephalography monitoring was able to predict poor neurologic outcomes at PICU discharge, with an area under the receiver operating characteristic curve of 0.91 (95% CI, 0.81-1.00)., Conclusions: Early amplitude-integrated electroencephalography monitoring may help predict poor neurologic outcomes in children within 24 hours following cardiac arrest.

Background: Central venous catheters (CVCs) provide a great comfort for hospitalized children. However, CVCs increase the risk of severe infection. As there are few data regarding pediatric epidemiology of catheter-related infections (CRIs), the main objective of this study was to measure the incidence rate of CRIs in our pediatric university hospital. We also sought to characterize the CRIs and to identify risk factors., Materials and Methods: We conducted an epidemiological prospective monocentric study including all CVCs, except Port-a-Caths and arterial catheters, inserted in children from birth to 18 years of age between April 2015 and March 2016 in the pediatric University Hospital of Nantes. Our main focus was the incidence rate of CRIs, defined according to French guidelines, while distinguishing between bloodstream infections (CRBIs) and non-bloodstream infections (CRIWBs). The incidence rate was also described for each pediatric ward. We analyzed the association between infection and potential risk factors using univariate and multivariate analysis by Cox regression., Results: We included 793 CVCs with 60 CRBIs and four CRIWBs. The incidence rate was 4.6/1000 catheter-days, with the highest incidence rate occurring in the neonatal intensive care unit (13.7/1000 catheter-days). Coagulase-negative staphylococci were responsible for 77.5% of the CRIs. Factors independently associated with a higher risk of infection in neonates were invasive ventilation and low gestational age., Conclusions: The incidence of CRIs in children hospitalized in our institution appears to be higher than the typical rate of CRIs reported in the literature. This was particularly true for neonates. These results should lead us to reinforce preventive measures and antibiotic stewardship but they also raise the difficulty of diagnosing with certainty CRIs in neonates., (Copyright © 2019 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: The use of extracorporeal membrane oxygenation (ECMO) in France has increased since the H1N1 pandemic in 2009. By contrast, neonatal and pediatric ECMO support in France was known to be limited to a few centers offering congenital cardiac surgery. The purpose of this survey conducted in 2017 was to identify the neonatal and pediatric ECMO centers in France as well as networks existing between ECMO and non-ECMO centers., Results: Seventy-two neonatal or pediatric intensive care unit medical directors answered the survey (84% of the centers surveyed). Twenty were identified as ECMO centers, defined as a unit able to start ECMO with its own resources. ECMO centers ranged from 470,000 to 1,180,000 inhabitants (neonates or children under 18). Thirteen of them (65%) reported that they were affiliated with a congenital cardiac surgery department. A total of 187 patients were supported with ECMO in these centers in 2016. Only six of these centers estimated an activity greater than 15 cases per year over the last 5 years. Nearly 30% of ECMO runs were indicated before or after congenital heart surgery. Four of the ECMO centers offered off-site facilities (mobile team). Non-ECMO centers are likely to be neonatal intensive care units. Nine of them (18.7%) declared knowing an ECMO center that provided mobile care with predefined organization, 11 (22.9%) reported knowing an ECMO center providing a mobile activity without predefined organization, nine (18.%), and 18 (37.5%) ICUs declared they knew of the existence of an ECMO program but did not report any possibility of mobile care or any procedure for transfer., Conclusions: Of the centers reporting the highest case volumes, four offered mobile ECMO abilities. Well-organized networks for the most severe neonates and children were not identified in France., (Copyright © 2019 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Properdin (FP) is a positive regulator of the immune system stimulating the activity of the proteolytically active C3 convertase C3bBb in the alternative pathway of the complement system. Here we present two crystal structures of FP and two structures of convertase bound FP. A structural core formed by three thrombospondin repeats (TSRs) and a TB domain harbors the convertase binding site in FP that mainly interacts with C3b. Stabilization of the interaction between the C3b C-terminus and the MIDAS bound Mg 2+ in the Bb protease by FP TSR5 is proposed to underlie FP convertase stabilization. Intermolecular contacts between FP and the convertase subunits suggested by the structure were confirmed by binding experiments. FP is shown to inhibit C3b degradation by FI due to a direct competition for a common binding site on C3b. FP oligomers are held together by two sets of intermolecular contacts, where the first is formed by the TB domain from one FP molecule and TSR4 from another. The second and largest interface is formed by TSR1 and TSR6 from the same two FP molecules. Flexibility at four hinges between thrombospondin repeats is suggested to enable the oligomeric, polydisperse, and extended architecture of FP. Our structures rationalize the effects of mutations associated with FP deficiencies and provide a structural basis for the analysis of FP function in convertases and its possible role in pattern recognition.

Primary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung development, we studied a unique collection of samples obtained from deceased individuals with clinically and histopathologically diagnosed interstitial neonatal lung disorders: acinar dysplasia (n = 14), congenital alveolar dysplasia (n = 2), and other lethal lung hypoplasias (n = 10). We identified rare heterozygous copy-number variant deletions or single-nucleotide variants (SNVs) involving TBX4 (n = 8 and n = 2, respectively) or FGF10 (n = 2 and n = 2, respectively) in 16/26 (61%) individuals. In addition to TBX4, the overlapping ∼2 Mb recurrent and nonrecurrent deletions at 17q23.1q23.2 identified in seven individuals with lung hypoplasia also remove a lung-specific enhancer region. Individuals with coding variants involving either TBX4 or FGF10 also harbored at least one non-coding SNV in the predicted lung-specific enhancer region, which was absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. The occurrence of rare coding variants involving TBX4 or FGF10 with the putative hypomorphic non-coding SNVs implies a complex compound inheritance of these pulmonary hypoplasias. Moreover, they support the importance of TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in human lung organogenesis and help to explain the histopathological continuum observed in these rare lethal developmental disorders of the lung., (Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Surgical site infections (SSI) increase length of stay, morbidity, mortality and cost of hospitalization. Staphylococcus aureus (SA) carriage is a known risk factor of SSI in adults, but its role in pediatrics remains uncertain. The main objective of this pilot prospective monocentric cohort study was to describe the prevalence of SA colonization in children under 1 year old before cardiac surgery. The secondary objectives were to compare the incidence of SSI and other nosocomial infections (NI) between preoperative carriers and non-carriers. From May 2012 to November 2013, all children <1 year old undergoing cardiac surgery under cardiopulmonary bypass underwent preoperative methicillin-resistant (MRSA) and methicillin-sensitive SA (MSSA) screening using real-time PCR. The only exclusion criterion was invalid PCR. All patients were followed up to 1 year after the surgery regarding SSI and other nosocomial infections. Among the 68 studied patients, SA colonization prevalence was 26.5%, comprising 23.5% MSSA and 2.9% MRSA. There was no significant difference between colonized and non-colonized children regarding SSI rate (16.7 vs 20%; p = 0.53), but ventilator-associated pneumonia rate was significantly higher among the SA carriers (22.2 vs 2%; p < 0.05). The colonization rate was different depending on the age of the patients (p < 0.05). This pilot study highlights that colonization with MSSA is frequent whereas MRSA prevalence is low in our population. In this cohort, there was no association between SA colonization and SSI incidence but further studies are needed to analyze this association.

Objectives: To evaluate the impact of a nurse-driven sedation protocol on the length of mechanical ventilation, total daily doses of sedatives, and complications of sedation., Design: A single-center prospective before and after study was conducted from October 2010 to December 2013., Setting: Twelve-bed surgical and medical PICU of the university-affiliated hospital in Nantes, France., Patients: A total of 235 patients, between 28 days and 18 years old, requiring mechanical ventilation for at least 24 hours were included in the study; data from 194 patients were analyzed., Interventions: During the first study phase, no protocol was used. During the second phase, patients were sedated according to a nurse-driven protocol., Measurements and Main Results: In the whole population, the length of mechanical ventilation did not differ between protocol and control groups (protocol, 4 [3-8] vs control, 5 [3-7.5]; p = 0.44). Analyzing age subgroups, the length of mechanical ventilation was significantly shorter in the protocol group than in the control group in children older than 12 months (4 [3-8] vs 5 [2.75-11.25] d; p = 0.04). Daily dose of midazolam decreased during the protocol phase compared with the control phase (1 [0.56-1.8] and 1.2 [0.85-2.4] mg/kg/d, respectively; p = 0.02). No differences were shown regarding other daily dose of drugs. In the control group, 68% of children had more than 20% of COMFORT-behavior scale assessment under the target (oversedation) versus 59% in the protocol group (p = 0.139)., Conclusions: Implementation of a nurse-driven sedation protocol in a PICU is feasible and safe, allowed a decrease in daily dose of benzodiazepines, and decreased the duration of mechanical ventilation in older patients.

Background: Neurally Adjusted Ventilatory Assist (NAVA) is a mode of assisted mechanical ventilation that delivers inspiratory pressure proportionally to the electrical activity of the diaphragm. To date, no pediatric study has focused on the effects of NAVA on hemodynamic parameters. This physiologic study with a randomized cross-over design compared hemodynamic parameters when NAVA or conventional ventilation (CV) was applied., Methods: After a baseline period, infants received NAVA and CV in a randomized order during two consecutive 30-min periods. During the last 10 min of each period, respiratory and hemodynamic parameters were collected. No changes in PEEP, FiO 2 , sedation or inotropic doses were allowed during these two periods. The challenge was to keep minute volumes constant, with no changes in blood CO 2 levels and in pH that may affect the results., Results: Six infants who had undergone cardiac surgery (mean age 7.8 ± 4.1 months) were studied after parental consent. Four of them had low central venous oxygen saturation (ScvO 2  < 65 %). The ventilatory settings resulted in similar minute volumes (1.7 ± 0.4 vs. 1.6 ± 0.6 ml/kg, P = 0.67) and in similar tidal volumes respectively with NAVA and with CV. There were no statistically significant differences on blood pH levels between the two modes of ventilation (7.32 ± 0.02 vs. 7.32 ± 0.04, P = 0.34). Ventilation with NAVA delivered lower peak inspiratory pressures than with CV: -32.7 % (95 % CI: -48.2 to -17.1 %, P = 0.04). With regard to hemodynamics, systolic arterial pressures were higher using NAVA: +8.4 % (95 % CI: +3.3 to +13.6 %, P = 0.03). There were no statistically significant differences on cardiac index between the two modes of ventilation. However, all children with a low baseline ScvO 2 (<65 %) tended to increase their cardiac index with NAVA compared to CV: 2.03 ± 0.30 vs. 1.91 ± 0.39 L/min.m 2 (median ± interquartile, P = 0.07)., Conclusions: This pilot study raises the hypothesis that NAVA could have beneficial effects on hemodynamics in children when compared to a conventional ventilatory mode that delivered identical PEEP and similar minute volumes., Trial Registration: ClinicalTrials.gov Identifier: NCT01490710 . Date of registration: December 7, 2011.

We report a child and her mother affected by Marfan syndrome. The child presented with a phenotype of neonatal Marfan syndrome, revealed by acute and refractory heart failure, finally leading to death within the first 4 months of life. Her mother had a common clinical presentation. Genetic analysis revealed an inherited FBN1 mutation. This intronic mutation (c.6163+3&#95;6163+6del), undescribed to date, leads to exon 49 skipping, corresponding to in-frame deletion of 42 amino acids (p.Ile2014&#95;Asp2055del). FBN1 next-generation sequencing did not show any argument for mosaicism. Association in the same family of severe neonatal and classical Marfan syndrome illustrates the intrafamilial phenotype variability.

Emerging resistance to antibiotics shows no signs of decline. At the same time, few new antibacterials are being discovered. There is a worldwide recognition regarding the danger of this situation. The urgency of the situation and the conviction that practices should change led the Société de Réanimation de Langue Française (SRLF) and the Société Française d'Anesthésie et de Réanimation (SFAR) to set up a panel of experts from various disciplines. These experts met for the first time at the end of 2012 and have since met regularly to issue the following 67 recommendations, according to the rigorous GRADE methodology. Five fields were explored: i) the link between the resistance of bacteria and the use of antibiotics in intensive care; ii) which microbiological data and how to use them to reduce antibiotic consumption; iii) how should antibiotic therapy be chosen to limit consumption of antibiotics; iv) how can antibiotic administration be optimized; v) review and duration of antibiotic treatments. In each institution, the appropriation of these recommendations should arouse multidisciplinary discussions resulting in better knowledge of local epidemiology, rate of antibiotic use, and finally protocols for improving the stewardship of antibiotics. These efforts should contribute to limit the emergence of resistant bacteria.

Objectives: Recent data have suggested a link between plasma transfusion and the development of nosocomial infections in critically ill children. However, to our knowledge, no study has specifically focused on this association among children undergoing cardiac surgery. Thus, the main objective of this study was to analyze the relationship between plasma transfusion after cardiac surgery and the risk of nosocomial infections, including bloodstream infections, mediastinitis, and ventilator-associated pneumonia, in children younger than 1 year., Design: Observational single-center study., Setting: A 12-bed tertiary PICU in a university hospital in France., Patients: Children less than 1 year admitted after cardiac surgery under cardiopulmonary bypass between November 2007 and December 2012., Interventions: None., Measurements and Main Results: Data from 233 children were analyzed, of which 94 children (40%) had been transfused with plasma during their PICU stay. Fifty-six episodes of nosocomial infections (51 children) were reported, yielding a nosocomial infection ratio of 24%. The unadjusted odds ratio for developing nosocomial infections associated with plasma transfusion was 4.1 (95% CI, 2.1-7.9; p < 0.001). After adjusting for a propensity score, there was no difference between the two groups (adjusted odds ratio, 1.5; 95% CI, 0.5-4.0; p = 0.5)., Conclusion: Plasma transfusion following cardiac surgery under cardiopulmonary bypass was not independently associated with the development of nosocomial infections in children (< 1 yr old) after adjustment for a propensity score.

Drowning in sea water is an unusual cause of severe hypernatremia. We report the case of a 3.5-year-old boy who died 11h after drowning in sea water, with a serum sodium level of 178 mmoL/L. In this case, hypernatremia was aggravated by diarrhea and hyperglycemia with glycosuria. Usually, correction of acute hypernatremia must be quick and early, aiming at a reduction of serum sodium concentration of up to 1-2 mmoL per liter per hour., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: In continuous renal replacement therapy (CRRT), regional citrate anticoagulation offers an attractive alternative to heparinization, especially for children with a high bleeding risk., Methods: We report on a new management approach to CRRT using integrated citrate software and physiological sodium concentration solutions. Convective filtration was performed with pre-filter citrate anticoagulation using an 18 mmol/L citrate solution and a post-filter replacement fluid. The citrate flow rate was automatically adjusted to the blood flow rate by means of integrated citrate software. Similarly, calcium was automatically infused into children to maintain their blood calcium levels within normal range., Results: Eleven CRRT sessions were performed (330 h) in seven critically ill children aged 3-15 years (extreme values 15-66 kg). Disease categories included sepsis with multiorgan dysfunction (n = 2) and hemolytic uremic syndrome (n = 5). Median effluent dose was 2.1 (extreme values 1.7-3.3) L/h/1.73 m2. No session had to be stopped because of metabolic complications. Calcium levels, both in the circuits and in the circulating blood of the children, remained stable and secure., Conclusions: Regional citrate anticoagulation can be used in children with a body weight of >15 kg using integrated citrate software and commercially available solutions with physiological sodium concentrations in a safe, effective and convenient procedure.

Shock after protamine infusion are rare. We report here the case of a 6-day-old boy having presented severe and recurring hypotensions after protamine infusions during cardiac surgery under cardio pulmonary bypass. The physiopathology of these reactions is complex and, in the presented case, involved mechanism may not be anaphylactic., (Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)