Two pediatric cases of multisystem inflammatory-like syndrome following COVID-19 vaccination.

Multisystem inflammatory syndrome in children (MIS-C) is a novel post-infectious disease occurring in the context of SARS-CoV2 infection. COVID-19 vaccines have been authorized since December 2020, and adverse events including myocarditis have been reported following vaccination. We describe the cases of two pediatric patients presenting with clinical and laboratory features suggestive of MIS-C a few days after receiving their first dose of the Pfizer BNT162b2 vaccine. The outcome was favorable for both patients (after corticosteroid and immunoglobulin administration for one patient). These cases suggest an association between the COVID-19 vaccine and the occurrence of MIS-C.

Therapeutic approach to pediatric patients with acute chest syndrome: national multicenter survey of non invasive ventilation (NIV) and transfusion.

BACKGROUND: Intensive care units (ICUs) have seen a spike in the use of noninvasive ventilation (NIV) for many medical conditions. We sought to investigate the attitudes and clinical practice regarding the management of acute chest syndrome (ACS) with a focus on NIV in pediatric ICUs. METHOD: Members of the French Group for Pediatric Intensive Care Emergencies (GFRUP) were asked to complete an online survey on physicians' attitudes toward children with ACS admitted to the PICU during 2015. RESULTS: The survey was answered by teams from 17 PICUs (240 beds). In total, 15 centers (88%) had a local transfusion unit and 14 (82%) worked in connection with a sickle cell disease (SCD) reference center. During 2015, 360 patients with SCD were managed (median: 7 per center; 21) of whom 137 (38%) for an ACS (median: 4 ACS per center; 8). The median length of PICU stay for ACS was 5 days (3.1). Among the 137 patients who presented with ACS, 73 (53%) received simple blood transfusion and 16 (12%) received exchange transfusion. For patients who required noninvasive ventilatory support, NIV with bilevel pressure (BiPAP) was the most frequent method (n = 68, 50%), followed by continuous positive airway pressure (CPAP) (n = 23, 17%) and high-flow oxygen (n = 21, 15%). The proportion of patients on BiPAP was up to 71% in the centers most frequently managing ACS patients. CONCLUSION: BiPAP is commonly used in PICUs for SCD patients with ACS, especially in trained centers. Future physiological studies and randomized controlled trials might help to choose the best ventilatory support for ACS.

Childhood epidermal necrolysis and erythema multiforme major: a multicentre French cohort study of 62 patients.

INTRODUCTION: The distinction between epidermal necrolysis [EN; including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities. MATERIALS AND METHODS: This French retrospective multicentre study included children ≤18 years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow-up. RESULTS: We included 62 children [43 boys, median age 10 years (range 3-18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P < 0.001), but 35% of cases remained idiopathic (TEN/overlap, 47%; SJS, 24%; EMM, 34%). The typical target lesions predominated in EMM (P < 0.001), the trunk was more often affected in EN (P < 0.001), and the body surface area involved was more extensive in EN (P < 0.001). Mucosal involvement did not differ between the groups. Two patients with idiopathic TEN died. Histology of EMM and EN showed similar features. The recurrence rate was 42% with EMM, 7% with TEN/overlap and 0 with SJS (P < 0.001). Sequelae occurred in 75% of EN but involved 55% of EMM. CONCLUSION: Clinical features of EN and EMM appeared well demarcated, with few overlapping cases. Idiopathic forms were frequent, especially for EN, meaning that a wide and thorough infectious screening, repeated if needed, is indicated for all paediatric cases of EN/EMM without any trigger drug. We propose a comprehensive panel of investigations which could be a standard work-up in such situation. Sequelae affected both EN and EMM.

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus.

OBJECTIVES: Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens. METHODS: We included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 ×MIC. RESULTS: Thirty-nine patients with a median (range) age of 7 (0.1-17) years and a BW of 21 (2.8-79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% fT> 4 ×MIC. CONCLUSIONS: In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 ×MIC in children with normal and augmented renal function.

Simple actions to support breastfeeding can avoid unwanted weaning in infants younger than 6 months hospitalized for bronchiolitis: A before/after study (Bronchilact II).

BACKGROUND: Admission to hospital with bronchiolitis may adversely affect breastfeeding. Correct advice and support have been pointed out as a determining factor. OBJECTIVES: We conducted a telephone survey to evaluate a set of actions to promote breastfeeding during hospitalization for acute bronchiolitis. METHODS: Population: All patients 6 months of age or younger hospitalized with acute bronchiolitis and receiving at least partial breastfeeding were eligible for the study. Patients discharged home whose parents accepted to be contacted by phone were also included. INTERVENTION: We established a set of actions to promote breastfeeding (posters, flyers, staff training, and equipment) in all pediatric wards attending to these patients. COMPARISON: This was a cross-sectional study conducted during two epidemic seasons of bronchiolitis in a tertiary care hospital. Data on continued breastfeeding at 3 months (0.5-6; median, range) postdischarge were collected by telephone and compared with the same set of data collected from patients with bronchiolitis in the same setting the year before the intervention. OUTCOME: We conducted a telephone survey to evaluate whether some actions regarding breastfeeding might diminish the risk of unwanted weaning during hospitalization for bronchiolitis. The primary outcome was the proportion of stopped or reduced breastfeeding at discharge. Secondary objectives were to evaluate whether there were factors associated with breastfeeding modification. RESULTS: The results of the evaluation before intervention (phase 1) are published by Heilbronner et al. In Phase 1 of our study, 84 patients were included and 43 mothers (51%) reported that breastfeeding was modified by hospitalization of their child: 20.4% stopped, 14% switched to partial breastfeeding, and 16.6% reduced breastfeeding. These mothers stated that causes of breastfeeding disturbances were lack of support and advice (63%), followed by severity of the child's respiratory disease (32%), logistical hospital difficulties (30%), and personal organizational issues (9.3%). The intervention took place in September. After the intervention, 50 patients could be included in the study between October 1and December 31, 2016. Among them, 40 (80%) mothers kept breastfeeding as before, four (8%) stopped, four (8%) switched to partial breastfeeding, and two (4%) reduced breastfeeding without stopping. Bronchiolitis was more severe among patients with altered breastfeeding in terms of ventilatory support. CONCLUSION: Bronchiolitis is a high-risk event for breastfeeding disruption but interventions to promote breastfeeding might help to prevent the risk of unwanted weaning. More severe bronchiolitis probably poses the highest risk of weaning and the need for supplementary nutrition.

Severe and fatal forms of COVID-19 in children.

OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.

Management of 35 critically ill hyperammonemic neonates: Role of early administration of metabolite scavengers and continuous hemodialysis.

Neurological involvement is frequent in inherited metabolic disease of the intoxication type. Hyperammonemic coma related to these diseases may cause severe neurological sequelae. Early optimal treatment is mandatory combining metabolite scavengers (MS) and sometimes continuous veno-venous hemodialysis (CVVHD). We aimed to describe the therapeutic management of hyperammonemia in neonates upon diagnosis of their metabolic disease and to compare neonates managed with MS alone or with both MS and CVVHD. We conducted a retrospective study including all neonates admitted for initial hyperammonemia to the pediatric intensive care unit of a Reference Center of Inherited Metabolic Diseases, between 2001 and 2012. The study included 35 neonates. Before admission, MS were initiated for 11 neonates. At admission, the median ammonia levels were 391 µmol/L and were significantly lower in neonates who received MS before admission. At admission, ammonia levels were 644 µmol/L in dialyzed and 283 µmol/L in non-dialyzed neonates. The median time to reach a 50% decrease of the initial ammonia levels was significantly shorter in dialyzed neonates; however, the normalization of ammonia levels was similar between dialyzed and non-dialyzed neonates. Hemodynamic disorders were more frequent in dialyzed neonates. CONCLUSION: MS represent an effective treatment for hyperammonemia and should be available in all pediatric units to avoid the need for CVVHD. Although CVVHD enhances the kinetics of toxic metabolite decrease, it is associated with adverse hemodynamic effects.

Diagnostic evaluation and management of seizures and status epilepticus in children with known epilepsy or new-onset seizures: A retrospective and comparative analysis.

OBJECTIVES: The purpose of this study was to describe and compare the initial management, including clinical/biological investigation and treatment, of new-onset seizures and status epilepticus (SE) in children versus seizures and SE in those with known epilepsy. METHODS: This was a retrospective, single-center, observational study conducted in an urban pediatric hospital in Paris. All patients, aged from 1 month to 18 years, admitted to the pediatric intensive care unit, the high-dependency care unit, and those who required hospitalization in the short-term unit of the emergency department between January 1 and December 31, 2014 for seizures and/or SE were included. RESULTS: We analyzed the data of 190 children: new-onset seizures (N=118; group A) versus those with known epilepsy (N=72; group B). At least one diagnostic test was performed on 156 patients (82.1%) (group A, N=104, 88.1%; group B, N=52, 72.2%; P=0.05). In group B, blood levels of antiepileptic drugs were measured in 14 of the 38 patients with SE, of whom six were under dosed. Treatments were: first line, diazepam (group A, 80%; group B, 46%; P<0.001); second line, diazepam (group A, 56%; group B, 34%; P=0.02) or clonazepam (group A, 24%; group B, 46%; P=0.001); third line, phenytoin (group A, 54%; group B, 22%; P<0.001) or clonazepam (group A, 18%; group B, 61%; P<0.001). CONCLUSION: Diagnostic evaluation and treatment should be individualized for children with known epilepsy.

Report of severe accidental baclofen intoxication in a healthy 4-year-old boy and review of the literature.

The number of reports on baclofen intoxication has increased in recent years. Here we report the case of a 4-year-old boy in deep coma who was referred to the pediatric intensive care unit. The patient was intubated and mechanically ventilated. A computerized tomography scan without contrast showed a collapsed appearance of the ventricular system suggesting diffuse cerebral edema. A multichannel electroencephalogram registered 6 h after admission showed a very slow and ample continuous pattern, without structure, nonreactive to stimulations, expressing diffuse and severe nonspecific cerebral pain. A targeted analysis to determine the baclofen plasma levels was performed. Test results of plasma samples were highly positive for baclofen (2009 ng/mL). Following 36 h of mechanical ventilation, the patient rapidly regained consciousness and recovered normal neurological behavior. The present case demonstrates the importance of considering baclofen overdosage in cases of deep coma with areflexia, and emphasizes the importance of warning parents about the potential toxicity of baclofen when prescribing the drug to a family member. A review of the literature on pediatric baclofen overdose is included.

The role of the neuropediatrician in pediatric intensive care unit: Diagnosis, therapeutics and major participation in collaborative multidisciplinary deliberations about life-sustaining treatments' withdrawal.

BACKGROUND: In Pediatric Intensive Care Unit (PICU) two types of population require the intervention of neuropediatricians (NP): chronic brain diseases' patients who face repetitive and prolonged hospitalizations, and patients with acute brain failure facing the risk of potential neurologic sequelae, and both conditions may result in a limitation of life-sustaining treatments (LLST) decision. OBJECTIVE: To assess NP's involvement in LLST decisions within the PICU of a tertiary hospital. METHOD: Retrospective study of medical reports of patients hospitalized during 2014 in the Necker-Hospital PICU. Patients were selected using keywords ("cardiorespiratory arrest", "death", "withdrawal of treatment", "palliative care", "acute brain failure", or "chronic neurological disease"), and/or if they were assessed by a NP during the hospitalization. Demographic and medical data were analysed, including the NP's assessment and data about Collaborative Multidisciplinary Deliberation (CMD) to discuss potential LLST. RESULTS: Among 1160 children, 274 patients were included and 142 (56%) were assessed by a NP during their hospitalization for diagnosis (n = 55) and/or treatment (n = 95) management. NP was required for 59%-100% of patients with neurological acute failure, and for 14-44% of patients with extra neurological failure. A LLST decision was taken after a CMD for 27 (9.8%) of them, and a NP was involved in 19/27 (70%) of these decisions that occurred during the hospitalization (n = 19) or before (n = 8).12 patients died thereafter the LLST decision (40% of the 30 dead patients). CONCLUSION: NP are clearly involved in the decision-process of LLST for patients admitted in PICU, claiming for close collaboration to improve current practices and the quality of the care provided to children.

Early Recruitment of Cerebral Microcirculation by Neuronal Nitric Oxide Synthase Inhibition in a Juvenile Ischemic Rat Model.

BACKGROUND: The development of collateral circulation is proposed as an inherent compensatory mechanism to restore impaired blood perfusion after ischemia, at least in the penumbra. We have studied the dynamic macro- and microcirculation after ischemia-reperfusion in the juvenile rat brain and evaluated the impact of neuronal nitric oxide synthase (nNOS) inhibition on the collateral flow. METHODS: Fourteen-day-old (P14) rats were subjected to ischemia-reperfusion and treated with either PBS or 7-nitroindazole (7-NI, an nNOS inhibitor, 25 mg/kg). Arterial blood flow (BF) was measured using 2D-color-coded pulsed ultrasound imaging. Laser speckle contrast (LSC) imaging and sidestream dark-field videomicroscopy were used to measure cortical and microvascular BF, respectively. RESULTS: In basal conditions, 7-NI reduced BF in the internal carotids (by ∼ 25%) and cortical (by ∼ 30%) BF, as compared to PBS. During ischemia, the increased mean BF velocity in the basilar trunk after both PBS and 7-NI demonstrated the establishment of collateral support and patency. Upon re-flow, BF immediately recovered to basal values in the internal carotid arteries under both conditions. The 7-NI group showed increased collateral flow in the penumbral tissue during early re-flow compared to PBS, as shown with both LSC imaging and side-stream dark-field videomicroscopy. The proportion of perfused capillaries was significantly increased under 7-NI as compared to PBS when given before ischemia (67.0 ± 3.9 vs. 46.8 ± 8.8, p < 0.01). Perfused capillaries (63.1 ± 17.7 vs. 81.1 ± 20.7, p < 0.001) and the BF index (2.4 ± 0.6 vs. 1.3 ± 0.1, p < 0.001) significantly increased under 7-NI given at the re-flow onset. CONCLUSIONS: Collateral support in the penumbra is initiated during ischemia, and may be increased during early re-flow by neuronal NOS inhibition (given in pre- and post-treatment), which may preserve brain tissue in juvenile rats.

Sudden deaths in adult-worn baby carriers: 19 cases.

Soft infant carriers such as slings have become extremely popular in the west and are usually considered safe. We report 19 cases of sudden unexpected death in infancy (SUDI) linked to infant carrier. Most patients were healthy full-term babies less than 3 months of age, and suffocation was the most frequent cause of death. CONCLUSION: Infant carriers represent an underestimated cause of death by suffocation in neonates. WHAT IS KNOWN: • Sudden unexpected deaths in infancy linked to infant carrier have been only sparsely reported. WHAT IS NEW: • We report a series of 19 cases strongly suggesting age of less than 3 months as a risk factor and suffocation as the mechanism of death.

[VRS bronchiolitis with severe hyponatremia leading to acute seizures: a report of three cases]. / Convulsions hyponatrémiques et bronchiolite à VRS : à propos de 3 cas.

Acute bronchiolitis due to respiratory syncytial virus (RSV) can present with extrapulmonary manifestations, notably severe hyponatremia. Hyponatremia is caused by excess secretion of antidiuretic hormone and can be exacerbated by intravenous infusion of hypotonic solutions. We report three cases of infants admitted for acute bronchiolitis and hyponatremia leading to acute seizures. We describe how hyponatremia was corrected and analyze the management aspects that might have worsened the magnitude of hyponatremia. We underline the basic principles of water and electrolyte management of bronchiolitis.

A pilot study comparing two polymethylpentene extracorporeal membrane oxygenators.

OBJECTIVE: We compared two polymethylpentene oxygenators being used in our unit: the Maquet Quadrox-iD paediatric and the Medos Hilite 800LT. STUDY DESIGN: A mono-centric, prospective pilot study was conducted on ten consecutive newborn patients who had been admitted to our hospital service for extracorporeal circulation (EC) treatment. We examined the rate of oxygen transfer, the CO2 removal capacity and the average sweep gas flow required to produce this result. We also assessed the disturbances of haemostasis, the need for labile blood products and the membrane oxygenator lifetime and cost of use. CONCLUSIONS: According to our study, it seems to us that Medos Hilite 800LT membrane oxygenators demonstrate greater oxygen transfer and CO2 removal capacity than Maquet Quadrox-iD paediatric membrane oxygenators, at a similar cost. These results lead us to conclude that it is reasonable to continue using Medos Hilite 800LT membrane oxygenators. A broader comparison study would be necessary in order to support these initial results.

[Particularities of ECMO in acute respiratory distress syndrome in pediatrics]. / Particularités de l'ECMO pour le syndrome de détresse respiratoire aiguë en pédiatrie.

Since the 80's, extracorporeal techniques have been used in pediatrics for the most severe acute respiratory distress syndromes. In 2012, data from the International Register of the Extracorporeal Life Support Organization revealed that more than 5,000 children had undergone extracorporeal membrane oxygenation (ECMO) with an increase in the number of annual cases since the epidemics of 2009. The survival rate (56%) is stable while the number of children with comorbidities increases due to the improvements in the equipment. Although there are no randomized studies, results encourage considering ECMO in pediatric ARDS. If veno-venous ECMO should be preferred in respiratory diseases, veno-arterial ECMO may be necessary and is still used frequently in children (50% of cases). In pediatrics, the technical features are first related to the physiological characteristics of the child and secondly to the technical limitations of the available equipment in the different ages. ECMO is a technique requiring specific expertise and specialized pediatric teams due to children's particularities.

[Enterocolitis as a complication of late-diagnosed Hirschsprung disease]. / Entérocolite compliquant une maladie de Hirschsprung diagnostiquée tardivement.

Enterocolitis is the most serious complication of Hirschsprung disease. Early management of these patients can decrease the severity of this complication. Hirschsprung disease is more common in patients with trisomy 21 than in the general population. Furthermore, the risk of developing enterocolitis is higher in this population. We report on an infant with trisomy 21 who developed enterocolitis as a complication of Hirschsprung disease that was diagnosed late when the infant presented with septic shock leading to death of the patient.

Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor.

Brain protection of the newborn remains a challenging priority and represents a totally unmet medical need. Pharmacological inhibition of caspases appears as a promising strategy for neuroprotection. In a translational perspective, we have developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563, which reaches the brain, and inhibits caspases activation, mitochondrial release of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects newborn rodent brain against excitotoxicity, hypoxia-ischemia, and perinatal arterial stroke with a 6-h therapeutic time window, and has no adverse effects on physiological parameters. Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns.

[Coagulase-negative staphylococcal osteomyelitis in preterm infants: a proposal for a diagnostic procedure]. / Ostéomyélites à staphylocoque coagulase négative chez le prématuré : proposition de démarche diagnostique.

Acute osteomyelitis, although a rare complication in neonates, is a diagnostic and therapeutic challenge. Successful treatment to avoid functional sequelae depends on early recognition of infection and rapid initiation of therapy. Although Staphylococcus aureus is the most common causative agent, coagulase-negative Staphylococcus (CONS), well known for bloodstream infection, can be involved in neonatal osteomyelitis. Risk factors of osteomyelitis include prematurity and invasive procedures, such as long-term central venous catheterization. We report on 3 cases of acute CONS osteomyelitis in preterm infants presenting with prolonged CONS bacteremia. Bacteremia persisted despite antibiotic treatment in accordance with antibiograms and despite removal of the intravascular device. All catheter cultures were negative and osteomyelitis was not located on the limb where the central catheter had been inserted in all cases. Osteomyelitis diagnosis may be difficult in neonates because of the paucity of clinical signs. In our observations, (99m)Tc scintigraphy was the key investigation for diagnosis and detection of multiple sites of bone infection. The place of this investigation is discussed in relation to other imaging techniques. These observations suggest that in the context of persisting CONS bacteremia, a secondary bone infection should be considered. Scintigraphy is a discriminating diagnostic tool.