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Objectives: Virulence factors of the causative agent, Bordetella pertussis, may be involved in fulminant pertussis, the most severe form of whooping cough (pertussis) in infants. We aimed to assess the association between fulminant pertussis and the status of pertactin (PRN) production of B. pertussis clinical isolates., Methods: Symptomatic infants aged <6 months with a positive B. pertussis culture from 2008-2019 were included. B. pertussis isolates and clinical data were collected from French hospital laboratories through the national pertussis surveillance network. Fulminant pertussis was defined as a case with a leukocyte count >40 × 10 9 /L and at least one of the following criteria: respiratory failure, pulmonary hypertension, shock, or multiple organ failure. PRN production was assessed by western blotting. Baseline characteristics of infants and microbiological findings were compared between patients with and without fulminant pertussis. To identify patient and microbiological features associated with fulminant pertussis, a multivariable modified Poisson regression model was developed with confounders selected using a directed acyclic graph., Results: We included 361 infants with pertussis (median age 63 days [interquartile range, 39-86]), of whom 32 (9%) progressed to fulminant pertussis. None of the mothers was vaccinated during pregnancy. Of the 361 implicated B. pertussis isolates, 294 (81%) produced PRN. Patients with fulminant pertussis were more often neonates (adjusted relative risk [aRR]: 3.62, 95% confidence interval [CI]: 1.76-7.44), infants with a history of prematurity (aRR: 7.08, 95% CI: 3.06-16.36), unvaccinated infants (aRR: 4.42, 95% CI: 1.02-19.24), and infants infected by PRN-producing isolates (aRR: 3.76, 95% CI: 1.02-13.83)., Discussion: PRN-producing B. pertussis was independently associated with an increased risk of fulminant pertussis. In a context where PRN-containing acellular pertussis vaccines favour the emergence of PRN-deficient isolates, our study suggests a positive role for such vaccines in driving the evolution of B. pertussis populations towards reduced virulence., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors report no relevant disclosures., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Fluid administration to increase stroke volume index (SVi) is a cornerstone of haemodynamic resuscitation. We assessed the accuracy of SVi variation during a calibrated abdominal compression manoeuvre (ΔSVi-CAC) to predict fluid responsiveness in children., Methods: Patients younger than 8 yr with acute circulatory failure, regardless of their ventilation status, were selected. SVi, calculated as the average of five velocity-time integrals multiplied by the left ventricular outflow tract surface area, was recorded at four different steps: baseline, after an abdominal compression with a calibrated pressure of 25 mm Hg, after return to baseline, and then after a volume expansion (VE) of 10 ml kg -1 lactated Ringer solution over 10 min. Patients were classified as responders if SVi variation after volume expansion (ΔSVi-VE) increased by at least 15%., Results: The 39 children included had a median [inter-quartile range (IQR)] age of 9 [5-31] months. Twenty patients were fluid responders and 19 were non-responders. ΔSVi-CAC correlated with ΔSVi-VE (r=0.829; P<0.001). The area under the receiver operating characteristic curve (ROC AUC ) was 0.94 [95% confidence interval (CI), 0.85-0.99]. The best threshold for ΔSVi-CAC was 11% with a specificity of 95% [95% CI, 84-100] and a sensitivity of 75% [95% CI, 55-95]. ROC AUC of respiratory variation of IVC diameter (ΔIVC) was 0.53 [95% CI, 0.32-0.72]., Conclusion: ΔSVi-CAC during abdominal compression was a reliable method to predict fluid responsiveness in children with acute circulatory failure regardless of their ventilation status., Clinical Trials Registration: CPP Lyon sud est II: n° ANSM 2015-A00388-41 Clinicaltrial.gov: NCT02505646., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: A child with severe combined immunodeficiency (SCID) had an influenza A(H1N1)pdm09 infection with viral excretion longer than 6 months, during 2013-2014 influenza season, despite cord blood transplantation and antiviral treatments., Methods: Conventional real-time RT-PCR methods were used to estimate viral load and to detect the presence of the common N1 neuraminidase (NA) H275Y substitution responsible for oseltamivir resistance. Next-generation sequencing (NGS) of influenza viruses was performed retrospectively to characterize viral quasispecies in specimens., Results: The patient was first treated with oral oseltamivir, leading to detection of low-levels of NA-H275Y substitution. Concomitant cord blood cell transplantation, intravenous administration of zanamivir and immunoglobulins led to an increase in white blood cells and influenza viral load decrease. A viral rebound occurred as soon as the antiviral treatment was discontinued. Eventually, influenza viral load was negated with immune reconstitution. NGS found influenza quasispecies harboring NA-E119A substitution (10.3%). Moreover, NGS showed that viral genomic diversity evolved under antiviral treatment and immune status., Conclusions: Conventional virological techniques were sufficient for influenza infection follow-up but NGS performances allowed characterization of viral variants evolution in this specific case of prolonged influenza virus infection. New and efficient treatments against influenza in immunocompromised patients are needed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Thrombotic microangiopathy (TMA) is a severe complication after hematopoietic stem cell transplantation (HSCT), with the reported mortality rate in such cases usually reaching 90%., Cases: We report on two pediatric cases of patients successfully treated by eculizumab for severe HSCT-TMA, occurring in two girls (8.4 and 3.6 years). The first patient developed TMA with hematologic abnormalities and renal/pulmonary lesions after allogeneic HSCT for Philadelphia-positive acute lymphoblastic leukemia; she received eculizumab 7 months after HSCT, with a dramatic improvement of renal function. The second patient developed severe TMA (cardiac tamponade, renal failure requiring dialysis, gastritis) after autologous HSCT for metastatic neuroblastoma. She received eculizumab for 7 months, with a dramatic improvement of renal function. No side effects were observed., Conclusion: The use of eculizumab as first-line therapy in pediatric patients with severe HSCT-TMA with multisystemic lesions appears promising. Larger international studies are required to confirm its benefit and safety for this specific indication., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: To compare management of injured children in an adult trauma center (TC) with competencies in pediatric trauma care (2005-2007) and in a pediatric-only trauma center (2010-2012)., Study Design: A before-after retrospective study., Patients and Methods: Fifty-nine children between 1 and 15 years of age admitted to the adult TC (2005-2007) were compared to 56 children admitted to the pediatric TC (2010-2012). Epidemiological data, severity scores, early outcome, and care duration in trauma resuscitation before whole-body CT were collected and compared between the two periods., Results: This study found no significant differences between the two periods in terms of care duration before the whole-body CT scan (28 min [18-40] vs 26.5 min [21-36], P=0.89) and early mortality (eight children [13.5%] vs ten children [17.8%], P=0.35)., Conclusion: With no differences in early management of injured children demonstrated, this study validates the organization within our pediatric trauma center. The effectiveness of management of children between 1 and 15 years of age with severe trauma seems to be similar in the two contexts., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: Malnutrition, known as a cause of morbidity, has not been studied in children admitted to pediatric intermediate care units. This study aimed to describe the association between patients' nutritional status and the relative severity of illness that characterizes this population., Patients and Methods: In this prospective longitudinal study, a dedicated nutrition support team assessed the nutritional status of all children, aged 5 days to 18 years, admitted to our university pediatric intermediate care unit (Hôpital Femme-Mère-Enfants, Lyon, France) over one year (2012-2013). Weight, height, body mass index, weight-for-age ratio, height-for-age ratio, and the analysis of growth curves were collected at admission. We monitored patients' weight, which allowed us to detect malnutrition occurrence during the stay, and its progression up to 3 months after discharge., Results: A total of 459 patients were enrolled. Based on the analysis integrating all nutritional indices and the progression of growth curves, malnutrition at admission was detected in 23.8% of children (20.5% and 6.8% suffered from acute and chronic malnutrition, respectively). Based only on the body mass index, malnutrition was detected in 15.5% of children. Chronic disease appeared as a risk factor for malnutrition at admission (P=0.0001) and young age for acute malnutrition (P=0.04). The incidence of acquired malnutrition during the stay (in children with a length of stay > 5 days) was up to 26%, and dyspnea was the only risk factor identified. This population recovered with a normal nutritional status late (66% after 2 months and 16% after 3 months)., Conclusions: The prevalence of malnutrition is high in our pediatric intermediate care unit. The occurrence of acquired malnutrition during the stay is frequent. All children should benefit from systematic nutritional assessment at admission as well as careful monitoring during the stay and after discharge, to adapt early and individualized nutritional support., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Local anesthetic intoxication is an uncommon complication of regional anesthesia. We report the case of a 4-month-old infant who presented with generalized tonic-clonic seizure complicated by cardiac arrest secondary to a severe intoxication to local anesthesia. These complications were observed after a bilateral dorsal penile nerve block with lidocaine for circumcision in a non-hospital setting. This report emphasizes the potential risk of local anesthetic systemic toxicity in such circumstances and describes its treatment., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Deep vein thrombosis occurs in 30% of patients with essential thrombocythemia, but rarely at initial diagnosis. We report two pediatric patients with essential thrombocythemia revealed by atypical deep vein thrombosis. First, a 16-year-old girl presented Budd-Chiari syndrome revealed by a hemorrhagic shock. Clinical exam revealed isolated splenomegaly. A search for thrombophilia found a factor V Leiden homozygous mutation and a Jak2 mutation. Bone marrow biopsy confirmed the diagnosis of a myeloproliferative disorder. The second case, a 17-year-old girl, had a routine examination by her physician that revealed splenomegaly. Ultrasonography displayed thrombus in the splenic and portal vein. An isolated Jak2 mutation was found and a myeloproliferative disorder was confirmed by bone marrow biopsy. The diagnosis of myeloproliferative disorder was made in both patients presenting atypical venous thrombosis with a Jak2 mutation and confirmed by bone marrow biopsy. These initial presentations of myeloproliferative disorders are rare in childhood and possibly underdiagnosed., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Metabolic phenotyping consists in the identification of subtle and coordinated metabolic variations associated with various pathophysiological stimuli. Different analytical methods, such as nuclear magnetic resonance, allow the simultaneous quantification of a large number of metabolites. Statistical analyses of these spectra thus lead to the discrimination between samples and the identification of a metabolic phenotype corresponding to the effect under study. This approach allows the extraction of candidate biomarkers and the recovery of perturbed metabolic networks, driving to the generation of biochemical hypotheses (pathophysiological mechanisms, diagnostic tests, therapeutic targets…). Metabolic phenotyping could be useful in anaesthesiology and intensive care medicine for the evaluation, monitoring or diagnosis of life-threatening situations, to optimise patient managements. This review introduces the physical and statistical fundamentals of NMR-based metabolic phenotyping, describes the work already achieved by this approach in anaesthesiology and intensive care medicine. Finally, potential areas of interest are discussed for the perioperative and intensive management of patients, from newborns to adults., (Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Objectives: Leonetti Law of 2005 concerns procedures for questioning about the appropriateness of initiating or maintaining life-sustaining treatments. Decision of withdrawing and withholding treatment has long been practiced by neonatologists, adult and pediatricians intensivists. In this regard, the recommendations of societies encourage medical teams to assess their practices to improve them. Our evaluation is based on the document of the Ethics Committee of SRLF edited in 2010., Type of Study: We achieved a retrospective evaluation of professional practices of the transcription of our decisions of withdrawing and withholding treatment., Patients and Methods: This study included all children (95 patients) who have had a questioning about life-sustaining treatment of ICU between March 2008 and August 2011 in the pediatric intensive care unit of Children's Hospital of Lyon. Our evaluation is based on the document of the Ethics Committee of French Society of intensive care (SRLF) edited in 2010. We collected epidemiological data on children concerned by questioning about the appropriateness of initiating or maintaining LST and an evaluation of the transcription of our procedures for LST in our folders. Evaluation included 40 cases: 20 folders randomly selected prior an information meeting (January 2011) which were compared with 20 cases occurred consecutively after this information. This meeting was intended to remind recommendations of good practice and principal points of the law. The main assessment measure was the improvement of the practices respecting criteria of the document of the Ethics Committee of SRLF modified for pediatric care., Main Results: Epidemiological data on procedures are comparable to literature data. Concerning the evaluation of our practices before/after a briefing and highlighted a tendency to the improvement without statistically significance. The transcription of reflection and the arguments of decision of withdrawing and withholding treatment and evaluation of pain was the points who need improvement. Finally, despite the positive developments in the therapeutic use of analgesics and sedatives, pain continues to be undervalued., Conclusion: The evaluation of professional practices is recommended to improve the procedures of questioning about life-sustaining treatments have become an area of expertise in intensive care., (Copyright © 2012. Published by Elsevier SAS.)

Purpura fulminans (PF) and deep vein thrombosis are rare complications secondary to chicken pox disease. The presence of antibodies reflects an ongoing immunological process and requires specialized management. The present study reports a 4-year-old boy with no medical history who presented with purpura on the legs 10 days after chicken pox eruption. Laboratory tests showed a disseminated intravascular coagulation associated with low plasma protein C and S activities, and the presence of anti-protein S antibodies. A replacement therapy with protein C infusions and fresh frozen plasma was prescribed. The patient also underwent regular sessions of hyperbaric oxygen followed by the surgery. Fourteen days after the beginning of the purpuric lesions, he presented deep vein thrombosis (DVT) of the lower limbs and was treated with unfractionated heparin. This case report illustrates the pathophysiology of DVT occurring in a patient with chicken pox disease (i.e., acquired protein C and S deficiencies and anti-protein S autoantibodies) and emphasizes the utility of thrombophilia testing in order to better adapt treatment., (Copyright © 2011. Published by Elsevier SAS.)

The case of 3-year-old girl severely injured, as restrained car passenger in a road crash, is reported. She presented with isolated circulatory failure, without specific clinical signs except skin contusions corresponding to seat belt. Because of mediastinum enlargement on systematic chest X-ray, a pericardial effusion was suspected, which was confirmed by echography, rapidly complicated by an acute tamponade without visible cause on CT-scan. The radiological assessment showed a moderate peritoneal haemorrhage related to a splenic injury. A persistent haemodynamic instability required a pericardial puncture, after rapid sequence tracheal intubation of the child, but without clinical improvement, despite fluid bolus, red-blood cell transfusion and epinephrine infusion. The child was rapidly transferred to the cardiac operating room for sternotomy, which showed a right atrial laceration. The injury was repaired, allowing the child to survive without disability. Tamponade due to traumatic cardiac injury is extremely rare in children. The clinical diagnosis is particularly difficult to establish in the context of polytrauma. The classical symptoms of cardiac tamponade are rarely complete. The association of chest injury, isolated circulatory failure and enlargement of mediastinum at chest X-ray should alert the physician. As the severity of these injuries is high, a rapid and multidisciplinary management is required, as well as specific anaesthetics precautions., (2010 Elsevier Masson SAS. All rights reserved.)

The emergence of the influenza A(H1N1) 2009 virus prompted the development of sensitive RT-PCR detection methods. Most are real time RT-PCRs which can provide viral quantification. In this manuscript, we describe a universal influenza A RT-PCR targeting the matrix (M) gene, combined with an RNaseP RT-PCR. These PCRs allow the detection of all influenza A virus subtypes, including A(H1N1)2009, together with a real-time assessment of the quality of the specimens tested. These PCR procedures were evaluated on 209 samples collected from paediatric patients. Viral loads determined through Ct values were corrected according to the RNaseP Ct value. The mean viral load in the collected samples was estimated to be 6.84 log RNA copies/mL. For poor quality samples (RNaseP Ct > 27), corrections resulted in +3 to +8 Ct values for the M gene RT-PCR. Corrected influenza Ct values were lower in late samples. No correlation was established between viral loads and clinical severity or duration of disease.This study shows that real time RT-PCR targeting the matrix gene is a reliable tool for quantification of type A influenza virus but emphasises the need for sample quality control assessment through cellular gene quantification for reliable estimation of the viral load. This method would be useful for disease management when repeated specimens are collected from an infected individual.

Bacterial meningitis is still a serious disease with a high risk of mortality and sequels. The progress in antibiotic treatment has not improved the prognosis. Thus, optimizing the initial care and the treatment of the most severe cases should improve the outcome. No study has compared the outcome according to the level of care at the admission site. There is evidence that the most severe cases should be managed by critical care units. It seems reasonable to recommend initial admission of common cases to units able to provide intensive care. Most people now agree that fluid restriction has not demonstrated its efficiency, furthermore it might have deleterious effects. However, a fluid overload should be avoided. Maintaining cerebral perfusion is a key issue in the treatment of bacterial meningitis and requires monitoring both arterial blood pressure and intracranial pressure. Intracranial pressure monitoring is probably useful to optimize the treatment of the most severe cases. The aggressive treatments of cerebral edema have not been evaluated but seem, in some limited series, able to improve some life threatening situations. The benefit of systematic glycerol administration needs confirmation. Seizures should be treated with the usual medications. However, drugs with potentially deleterious effects on hemodynamics should be avoided. There is no sufficient evidence to support the administration of a systematic prophylactic treatment. Fever should be treated when above 39.5 degrees C/40 degrees C and in the case of intracranial hypertension. There is no clinical study to explore the modifications of fever on bacterial growth or on inflammation as observed in some experimental studies.

Objectives: The aim of this study was to systematically evaluate adverse drug reactions (ADRs) in children consulting at the pediatric emergency unit during a 6-month period., Method: The regional pharmacovigilance center (CRPV) and the department of clinical pharmacology prospectively and systematically recorded all potential ADRs among patients younger than 18 years of age in the pediatric emergency unit reported at the daily staff meetings. All cases were then screened and validated by the CRPV. For validated cases, preventability, seriousness, and off-label use were evaluated., Results: During the study period, from 1 March to 1 September 2005, 90 children presented potential adverse drug events. ADRs were confirmed in 43 patients, 19 females and 24 males. Thirty-four patients (79%) were under the age of 5. According to the European definition, 14 patients (33%) had serious ADRs. One anaphylactic shock after amoxicillin injection; antimalarial prophylaxis misuse leading to convulsive status epilepticus, convulsion, and coma after hepatitis B and MMR vaccines were deemed life-threatening. Three ADRs were considered avoidable. Antibiotics and vaccines were the most common possible cause of ADRs (76%). Skin reactions (n=27), fever (n=8), and gastric disorders (n=5) were the most common clinical manifestations., Conclusions: Because ADRs were reported by clinicians on a voluntary basis, serious ADRs were probably reported more systematically. Compared to a similar period without active monitoring, active drug monitoring of ADRs doubled the number of confirmed cases 43 vs 17, p<0.001. Close collaboration between the pharmacovigilance center, pharmacologists, and clinicians is necessary and seems feasible for improving the monitoring of ADRs in children.