Publications by authors named "Olivier Brissaud"

33 Publications

Brain MRI after therapeutic hypothermia in asphyxiated newborns: Predictive value at one year of imaging features.

Eur J Radiol 2021 Apr 15;139:109724. Epub 2021 Apr 15.

Service d'imagerie anténatale, de l'enfant et de la femme, Hôpital Pellegrin, place Amélie Raba-Léon, F-33076, Bordeaux, France; CRMSB, UMR5536 CNRS/Univ. Bordeaux, F-33076, Bordeaux, France. Electronic address:

Purpose: To compare early brain MRI using a composite imaging score and outcome at one year in asphyxiated newborns treated by hypothermia.

Methods: This retrospective study included for two years consecutive asphyxiated term newborns treated by hypothermia for hypoxic-ischemic encephalopathy, and who had brain MRI before day 8. Therapeutic hypothermia was initiated within the first 6 h of life and continued for 72 h. Imaging protocol included T1 and T2 sequences, diffusion-weighted imaging (DWI), evaluated with a specific composite score, and spectroscopy. Clinical evaluation was performed at one year of age, outcome was classified as favorable/unfavorable. The primary endpoint was the correlation between our MRI score and outcome with the definition of a threshold. The secondary endpoints were to find the most relevant criteria within the score and to evaluate objective signal measurements to support subjective criteria.

Results: Among the 33 included patients, 9 died during the first days of life, 20 had a favorable outcome, 4 an unfavorable one. MRI score was correlated to a poor clinical outcome (p < 0.001). Most of the criteria within the score and spectroscopy results were relevant (p < 0.05). Cerebral edema was objectively assessed by the signal intensity ratio of white matter compared to cerebrospinal fluid (CSF) on T2-weighted images (p < 0.001).

Conclusion: MRI score was predictive of neurodevelopmental outcome at one year. The most relevant criteria within the score were DWI abnormalities in basal ganglia and thalami and loss of white-cortical grey matter differentiation. Signal intensity ratio between white matter and CSF higher than 0.75 supports the presence of edema.
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http://dx.doi.org/10.1016/j.ejrad.2021.109724DOI Listing
April 2021

Necrotizing soft-tissue infections in pediatric intensive care: a prospective multicenter case-series study.

Crit Care 2021 04 12;25(1):139. Epub 2021 Apr 12.

Pediatric Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Service de Médecine Intensive - Réanimation Pédiatriques, Hôpital Universitaire Robert Debré, Université de Paris, 48 boulevard Sérurier, 75019, Paris, France.

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http://dx.doi.org/10.1186/s13054-021-03562-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040196PMC
April 2021

European Resuscitation Council Guidelines 2021: Paediatric Life Support.

Resuscitation 2021 Apr 24;161:327-387. Epub 2021 Mar 24.

Paediatric Emergency Medicine, Imperial College Healthcare Trust NHS, Faculty of Medicine Imperial College, London, UK.

These European Resuscitation Council Paediatric Life Support (PLS) guidelines, are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidelines on the management of critically ill infants and children, before, during and after cardiac arrest.
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http://dx.doi.org/10.1016/j.resuscitation.2021.02.015DOI Listing
April 2021

Ammonium salts are a reservoir of nitrogen on a cometary nucleus and possibly on some asteroids.

Science 2020 03;367(6483)

Dipartimento di Matematica e Fisica "E. De Giorgi," Università del Salento, Lecce, Italy.

The measured nitrogen-to-carbon ratio in comets is lower than for the Sun, a discrepancy which could be alleviated if there is an unknown reservoir of nitrogen in comets. The nucleus of comet 67P/Churyumov-Gerasimenko exhibits an unidentified broad spectral reflectance feature around 3.2 micrometers, which is ubiquitous across its surface. On the basis of laboratory experiments, we attribute this absorption band to ammonium salts mixed with dust on the surface. The depth of the band indicates that semivolatile ammonium salts are a substantial reservoir of nitrogen in the comet, potentially dominating over refractory organic matter and more volatile species. Similar absorption features appear in the spectra of some asteroids, implying a compositional link between asteroids, comets, and the parent interstellar cloud.
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http://dx.doi.org/10.1126/science.aaw7462DOI Listing
March 2020

Outcome of children with Shiga toxin-associated haemolytic uraemic syndrome treated with eculizumab: a matched cohort study.

Nephrol Dial Transplant 2020 12;35(12):2147-2153

Service de Pédiatrie, Unité de Néphrologie, Centre de référence Maladies Rénales Rares du Sud-ouest, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.

Background: Treatment with eculizumab in Shiga toxin-associated haemolytic and uraemic syndrome (STEC-HUS) remains controversial despite its increasing utilization. The aim of our study was to evaluate the outcomes of children treated with eculizumab for STEC-HUS in a single-centre matched cohort study.

Methods: Data were retrospectively collected from medical records of children diagnosed with STEC-HUS. The outcomes of patients treated with eculizumab for STEC-HUS were compared with those of a control group of untreated patients matched for age, sex and severity of acute kidney injury with a 1:2 matching scheme.

Results: Eighteen children (median age 40.6 months) with STEC-HUS treated with eculizumab were compared with 36 matched control patients (median age 36.4 months) who did not receive eculizumab. All patients survived in the two groups. Within 1 month of HUS onset, the evolution of haematological and renal parameters did not differ between the two groups. At 12 months of follow-up, renal outcome was not significantly different between the two groups. At the last follow-up, the prevalence of decreased glomerular filtration rate in the eculizumab group (27%) was not statistically different from that in controls (38%), as was the prevalence of proteinuria and high blood pressure. Children who received eculizumab more often had extrarenal sequelae during follow-up. Eculizumab treatment appeared to be safe in children with STEC-HUS.

Conclusion: The benefit of eculizumab on renal and extrarenal outcomes in STEC-HUS could not be established based on our findings. However, efficacy and safety are not best assessed by the observational design and small sample size of our study. Randomized controlled trials are thus required to determine the efficacy of eculizumab in this indication.
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http://dx.doi.org/10.1093/ndt/gfz158DOI Listing
December 2020

SHADOWS: a spectro-gonio radiometer for bidirectional reflectance studies of dark meteorites and terrestrial analogs: design, calibrations, and performances on challenging surfaces.

Appl Opt 2018 Oct;57(28):8279-8296

We have developed a new spectro-gonio radiometer, SHADOWS, to study in the laboratory the bidirectional reflectance distribution function of dark and precious samples. The instrument operates over a wide spectral range from the visible to the near-infrared (350-5000 nm) and is installed in a cold room to operate at a temperature as low as -20°. The high flux monochromatic beam is focused on the sample, resulting in an illumination spot of about 5.2 mm in diameter. The reflected light is measured by two detectors with high sensitivity (down to 0.005% in reflectance) and absolute accuracy of 1%. The illumination and observations angles, including azimuth, can be varied over wide ranges. This paper presents the scientific and technical constraints of the spectro-gonio radiometer, its design and additional capabilities, as well as the performances and limitations of the instrument.
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http://dx.doi.org/10.1364/AO.57.008279DOI Listing
October 2018

Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU.

Ann Intensive Care 2018 Nov 3;8(1):104. Epub 2018 Nov 3.

Département d'Anesthésie Réanimation, Centre Hospitalier Regional Universitaire de Montpellier, Montpellier, France.

Background: The French Society of Anaesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit. The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists.

Results: The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, post-operative and paediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases.

Conclusions: HAP should be prevented by a standardised multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram-negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.
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http://dx.doi.org/10.1186/s13613-018-0444-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215539PMC
November 2018

A multicenter randomized controlled trial of a 3-L/kg/min versus 2-L/kg/min high-flow nasal cannula flow rate in young infants with severe viral bronchiolitis (TRAMONTANE 2).

Intensive Care Med 2018 Nov 21;44(11):1870-1878. Epub 2018 Oct 21.

Department of Neonatal Medicine and Pediatric Intensive Care, Arnaud de Villeneuve University Hospital, 371 Avenue Doyen G Giraud, 34295, Montpellier Cedex 5, France.

Purpose: High-flow nasal cannula (HFNC) therapy is increasingly proposed as first-line respiratory support for infants with acute viral bronchiolitis (AVB). Most teams use 2 L/kg/min, but no study compared different flow rates in this setting. We hypothesized that 3 L/kg/min would be more efficient for the initial management of these patients.

Methods: A randomized controlled trial was performed in 16 pediatric intensive care units (PICUs) to compare these two flow rates in infants up to 6 months old with moderate to severe AVB and treated with HFNC. The primary endpoint was the percentage of failure within 48 h of randomization, using prespecified criteria of worsening respiratory distress and discomfort.

Results: From November 2016 to March 2017, 142 infants were allocated to the 2-L/kg/min (2L) flow rate and 144 to the 3-L/kg/min (3L) flow rate. Failure rate was comparable between groups: 38.7% (2L) vs. 38.9% (3L; p = 0.98). Worsening respiratory distress was the most common cause of failure in both groups: 49% (2L) vs. 39% (3L; p = 0.45). In the 3L group, discomfort was more frequent (43% vs. 16%, p = 0.002) and PICU stays were longer (6.4 vs. 5.3 days, p = 0.048). The intubation rates [2.8% (2L) vs. 6.9% (3L), p = 0.17] and durations of invasive [0.2 (2L) vs. 0.5 (3L) days, p = 0.10] and noninvasive [1.4 (2L) vs. 1.6 (3L) days, p = 0.97] ventilation were comparable. No patient had air leak syndrome or died.

Conclusion: In young infants with AVB supported with HFNC, 3 L/kg/min did not reduce the risk of failure compared with 2 L/kg/min. This clinical trial was recorded on the National Library of Medicine registry (NCT02824744).
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http://dx.doi.org/10.1007/s00134-018-5343-1DOI Listing
November 2018

Hospital-acquired pneumonia in ICU.

Anaesth Crit Care Pain Med 2018 Feb 15;37(1):83-98. Epub 2017 Nov 15.

Département d'anesthésie réanimation, hôpital de la Timone, 13000 Marseille, France; Département d'anesthésie réanimation, hôpital Saint-Eloi, CHU de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier cedex 5, France; Inserm U1046, CNRS UMR 9214, PhyMedExp, université de Montpellier, 34295 Montpellier cedex 5, France.

The French Society of Anesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit (ICU). The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists. The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, postoperative and pediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases. HAP should be prevented by a standardized multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.
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http://dx.doi.org/10.1016/j.accpm.2017.11.006DOI Listing
February 2018

Targeted temperature management in the ICU: Guidelines from a French expert panel.

Anaesth Crit Care Pain Med 2018 10 5;37(5):481-491. Epub 2017 Jul 5.

Service d'anesthésie-réanimation, hôpital de la Timone, Assistance publique-Hôpitaux de Marseille, Marseille, France.

Over the recent period, the use of induced hypothermia has gained an increasing interest for critically ill patients, in particular in brain-injured patients. The term "targeted temperature management" (TTM) has now emerged as the most appropriate when referring to interventions used to reach and maintain a specific level temperature for each individual. TTM may be used to prevent fever, to maintain normothermia, or to lower core temperature. This treatment is widely used in intensive care units, mostly as a primary neuroprotective method. Indications are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of TTM in adult and paediatric critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de réanimation de langue française [SRLF]) and the French Society of Anesthesia and Intensive Care Medicine (Société francaise d'anesthésie réanimation [SFAR]) with the participation of the French Emergency Medicine Association (Société française de médecine d'urgence [SFMU]), the French Group for Pediatric Intensive Care and Emergencies (Groupe francophone de réanimation et urgences pédiatriques [GFRUP]), the French National Association of Neuro-Anesthesiology and Critical Care (Association nationale de neuro-anesthésie réanimation française [ANARLF]), and the French Neurovascular Society (Société française neurovasculaire [SFNV]). Fifteen experts and two coordinators agreed to consider questions concerning TTM and its practical implementation in five clinical situations: cardiac arrest, traumatic brain injury, stroke, other brain injuries, and shock. This resulted in 30 recommendations: 3 recommendations were strong (Grade 1), 13 were weak (Grade 2), and 14 were experts' opinions. After two rounds of rating and various amendments, a strong agreement from voting participants was obtained for all 30 (100%) recommendations, which are exposed in the present article.
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http://dx.doi.org/10.1016/j.accpm.2017.06.003DOI Listing
October 2018

Targeted temperature management in the ICU: guidelines from a French expert panel.

Ann Intensive Care 2017 Dec 19;7(1):70. Epub 2017 Jun 19.

Service d'Anesthésie-Réanimation, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Over the recent period, the use of induced hypothermia has gained an increasing interest for critically ill patients, in particular in brain-injured patients. The term "targeted temperature management" (TTM) has now emerged as the most appropriate when referring to interventions used to reach and maintain a specific level temperature for each individual. TTM may be used to prevent fever, to maintain normothermia, or to lower core temperature. This treatment is widely used in intensive care units, mostly as a primary neuroprotective method. Indications are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of TTM in adult and paediatric critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de Réanimation de Langue Française [SRLF]) and the French Society of Anesthesia and Intensive Care Medicine (Société Francaise d'Anesthésie Réanimation [SFAR]) with the participation of the French Emergency Medicine Association (Société Française de Médecine d'Urgence [SFMU]), the French Group for Pediatric Intensive Care and Emergencies (Groupe Francophone de Réanimation et Urgences Pédiatriques [GFRUP]), the French National Association of Neuro-Anesthesiology and Critical Care (Association Nationale de Neuro-Anesthésie Réanimation Française [ANARLF]), and the French Neurovascular Society (Société Française Neurovasculaire [SFNV]). Fifteen experts and two coordinators agreed to consider questions concerning TTM and its practical implementation in five clinical situations: cardiac arrest, traumatic brain injury, stroke, other brain injuries, and shock. This resulted in 30 recommendations: 3 recommendations were strong (Grade 1), 13 were weak (Grade 2), and 14 were experts' opinions. After two rounds of rating and various amendments, a strong agreement from voting participants was obtained for all 30 (100%) recommendations, which are exposed in the present article.
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http://dx.doi.org/10.1186/s13613-017-0294-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476556PMC
December 2017

Pandemic influenza 2009: Impact of vaccination coverage on critical illness in children, a Canada and France observational study.

World J Clin Pediatr 2016 Nov 8;5(4):374-382. Epub 2016 Nov 8.

Olivier Fléchelles, Pediatric and Neonatal ICU, MFME Hospital, Fort de France, 97261 Martinique, France.

Aim: To study the impact of vaccination critical illness due to H1N1pdm09, we compared the incidence and severity of H1N1pdm09 infection in Canada and France.

Methods: We studied two national cohorts that included children with documented H1N1pdm09 infection, admitted to a pediatric intensive care unit (PICU) in Canada and in France between October 1, 2009 and January 31, 2010.

Results: Vaccination coverage prior to admission to PICUs was higher in Canada than in France (21% 2% of children respectively, < 0.001), and in both countries, vaccination coverage prior to admission of these critically ill patients was substantially lower than in the general pediatric population ( < 0.001). In Canada, 160 children (incidence = 2.6/100000 children) were hospitalized in PICU compared to 125 children (incidence = 1.1/100000) in France ( < 0.001). Mortality rates were similar in Canada and France (4.4% 6.5%, = 0.45, respectively), median invasive mechanical ventilation duration and mean PICU length of stay were shorter in Canada (4 d 6 d, = 0.02 and 5.7 d 8.2 d, = 0.03, respectively). H1N1pdm09 vaccination prior to PICU admission was associated with a decreased risk of requiring invasive mechanical ventilation (OR = 0.30, 95%CI: 0.11-0.83, = 0.02).

Conclusion: The critical illness due to H1N1pdm09 had a higher incidence in Canada than in France. Critically ill children were less likely to have received vaccination prior to hospitalization in comparison to general population and children vaccinated had lower risk of ventilation.
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http://dx.doi.org/10.5409/wjcp.v5.i4.374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099590PMC
November 2016

[The emotions of caregivers in neonatal and paediatric intensive care].

Soins Pediatr Pueric 2016 Jul-Aug;37(291):43-6

Unité de réanimation néonatale et pédiatrique, Hôpital des enfants, CHU Bordeaux, Place Amélie-Raba-Léon, 33000 Bordeaux, France.

When treating a child hospitalised in a neonatal or paediatric unit, the emotions of the child's parents are of particular concern for the caregivers. The emotional experience of the nursing teams, however, is rarely taken into account, despite it having an impact on the quality of the support. Group discussion and individual reflection around professionals' emotions is essential.
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http://dx.doi.org/10.1016/j.spp.2016.05.012DOI Listing
June 2017

Corrigendum: Protective effects of intermittent hypoxia on brain and memory in a mouse model of apnea of prematurity.

Front Physiol 2016 22;7:105. Epub 2016 Mar 22.

Inserm, U1141, Robert Debré HospitalParis, France; Paris Diderot-Paris 7 UniversityParis, France.

[This corrects the article on p. 313 in vol. 6, PMID: 26582992.].
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http://dx.doi.org/10.3389/fphys.2016.00105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802410PMC
April 2016

Experts' recommendations for the management of cardiogenic shock in children.

Ann Intensive Care 2016 Dec 16;6(1):14. Epub 2016 Feb 16.

Service de Réanimation Médicale, Hôpital Émile-Muller, 68070, Mulhouse, France.

Cardiogenic shock which corresponds to an acute state of circulatory failure due to impairment of myocardial contractility is a very rare disease in children, even more than in adults. To date, no international recommendations regarding its management in critically ill children are available. An experts' recommendations in adult population have recently been made (Levy et al. Ann Intensive Care 5(1):52, 2015; Levy et al. Ann Intensive Care 5(1):26, 2015). We present herein recommendations for the management of cardiogenic shock in children, developed with the grading of recommendations' assessment, development, and evaluation system by an expert group of the Groupe Francophone de Réanimation et Urgences Pédiatriques (French Group for Pediatric Intensive Care and Emergencies). The recommendations cover four major fields of application such as: recognition of early signs of shock and the patient pathway, management principles and therapeutic goals, monitoring hemodynamic and biological variables, and circulatory support (indications, techniques, organization, and transfer criteria). Major principle care for children with cardiogenic shock is primarily based on clinical and echocardiographic assessment. There are few drugs reported as effective in childhood in the medical literature. The use of circulatory support should be facilitated in terms of organization and reflected in the centers that support these children. Children with cardiogenic shock are vulnerable and should be followed regularly by intensivist cardiologists and pediatricians. The experts emphasize the multidisciplinary nature of management of children with cardiogenic shock and the importance of effective communication between emergency medical assistance teams (SAMU), mobile pediatric emergency units (SMUR), pediatric emergency departments, pediatric cardiology and cardiac surgery departments, and pediatric intensive care units.
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http://dx.doi.org/10.1186/s13613-016-0111-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754230PMC
December 2016

Outbreak in newborns of methicillin-resistant Staphylococcus aureus related to the sequence type 5 Geraldine clone.

Am J Infect Control 2016 Feb 14;44(2):e9-11. Epub 2015 Nov 14.

Department of Infection Control, Groupe Hospitalier Pellegrin, University Hospital, Bordeaux, France; INSERM U657, University of Bordeaux, Bordeaux Cedex, France. Electronic address:

We describe the first nosocomial outbreak of a toxic shock syndrome-positive methicillin-resistant Staphylococcus aureus (MRSA) sequence type 5 Geraldine clone. Infection control interventions that are usually successful were implemented to control the outbreak. Spread of this virulent MRSA strain highlights the need to be vigilant to MRSA antibiotic susceptibilities.
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http://dx.doi.org/10.1016/j.ajic.2015.09.020DOI Listing
February 2016

Protective effects of intermittent hypoxia on brain and memory in a mouse model of apnea of prematurity.

Front Physiol 2015 4;6:313. Epub 2015 Nov 4.

Inserm, U1141, Robert Debré Hospital Paris, France ; Paris Diderot-Paris 7 University Paris, France.

Apnea of prematurity (AOP) is considered a risk factor for neurodevelopmental disorders in children based on epidemiological studies. This idea is supported by studies in newborn rodents in which exposure to intermittent hypoxia (IH) as a model of AOP significantly impairs development. However, the severe IH used in these studies may not fully reflect the broad spectrum of AOP severity. Considering that hypoxia appears neuroprotective under various conditions, we hypothesized that moderate IH would protect the neonatal mouse brain against behavioral stressors and brain damage. On P6, each pup in each litter was randomly assigned to one of three groups: a group exposed to IH while separated from the mother (IH group), a control group exposed to normoxia while separated from the mother (AIR group), and a group of untreated unmanipulated pups left continuously with their mother until weaning (UNT group). Exposure to moderate IH (8% O2) consisted of 20 hypoxic events/hour, 6 h per day from postnatal day 6 (P6) to P10. The stress generated by maternal separation in newborn rodents is known to impair brain development, and we expected this effect to be smaller in the IH group compared to the AIR group. In a separate experiment, we combined maternal separation with excitotoxic brain lesions mimicking those seen in preterm infants. We analyzed memory, angiogenesis, neurogenesis and brain lesion size. In non-lesioned mice, IH stimulated hippocampal angiogenesis and neurogenesis and improved short-term memory indices. In brain-lesioned mice, IH decreased lesion size and prevented memory impairments. Contrary to common perception, IH mimicking moderate apnea may offer neuroprotection, at least in part, against brain lesions and cognitive dysfunctions related to prematurity. AOP may therefore have beneficial effects in some preterm infants. These results support the need for stratification based on AOP severity in clinical trials of treatments for AOP, to determine whether in patients with moderate AOP, these treatments are beneficial or deleterious.
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http://dx.doi.org/10.3389/fphys.2015.00313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631942PMC
November 2015

[The role of the psychologist with a death in neonatal and paediatric intensive care].

Soins Pediatr Pueric 2014 Jul-Aug(279):33-6

The psychologist within a neonatal and paediatric intensive care unit intervenes in accordance with the condition of the patient and those at whom their services are aimed. The psychological practice in this particular context comprises certain specificities. As the child nears the end of life the psychologist must find his place within the unit and adapt his care to the needs expressed.
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November 2014

Diagnostic value of polymerase chain reaction analysis of skin biopsies in purpura fulminans.

Pediatr Dermatol 2013 Nov-Dec;30(6):e276-7. Epub 2013 Jul 9.

Pediatric Dermatology Unit, Hôpital Pellegrin-Enfants, Bordeaux, France; Department of Pediatrics, Hôpital Pellegrin-Enfants, Bordeaux, France.

Even though prompt diagnosis and treatment of purpura fulminans (PF) is essential to reduce mortality, early administration of antibiotics may preclude identification of the causative agent by standard bacterial cultures and thus render definitive diagnosis impossible. Here we present a case of an infant with PF and negative bacterial cultures for whom polymerase chain reaction (PCR) analysis of a cutaneous biopsy specimen obtained 4 days after initiation of antibiotics identified the genomic sequence of Neisseria meningitidis genogroup C. When bacterial cultures fail to provide useful information, PCR of skin biopsy specimens can be a valuable diagnostic tool in PF.
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http://dx.doi.org/10.1111/pde.12181DOI Listing
August 2014

Neuroprotective effects of dexmedetomidine against glutamate agonist-induced neuronal cell death are related to increased astrocyte brain-derived neurotrophic factor expression.

Anesthesiology 2013 May;118(5):1123-32

Inserm, U676, Paris, France, Université Paris 7, Paris, France.

Background: Brain-derived neurotrophic factor (BDNF) plays a prominent role in neuroprotection against perinatal brain injury. Dexmedetomidine, a selective agonist of α2-adrenergic receptors, also provides neuroprotection against glutamate-induced damage. Because adrenergic receptor agonists can modulate BDNF expression, our goal was to examine whether dexmedetomidine's neuroprotective effects are mediated by BDNF modulation in mouse perinatal brain injury.

Methods: The protective effects against glutamate-induced injury of BDNF and dexmedetomidine alone or in combination with either a neutralizing BDNF antibody or an inhibitor of the extracellular signal-regulated kinase pathway (PD098059) were compared in perinatal ibotenate-induced cortical lesions (n = 10-20 pups/groups) and in mouse neuronal cultures (300 μM of ibotenate for 6 h). The effect of dexmedetomidine on BDNF expression was examined in vivo and in vitro with cortical neuronal and astrocyte isolated cultures.

Results: Both BDNF and dexmedetomidine produced a significant neuroprotective effect in vivo and in vitro. Dexmedetomidine enhanced Bdnf4 and Bdnf5 transcription and BDNF protein cortical expression in vivo. Dexmedetomidine also enhanced Bdnf4 and Bdnf5 transcription and increased BDNF media concentration in isolated astrocyte cultures but not in neuronal cultures. Dexmedetomidine's protective effect was inhibited with BDNF antibody (mean lesion size ± SD: 577 ± 148 μm vs. 1028 ± 213 μm, n = 14-20, P < 0.001) and PD098059 in vivo but not in isolated neuron cultures. Finally, PD098059 inhibited the increased release of BDNF induced by dexmedetomidine in astrocyte cultures.

Conclusion: These results suggest that dexmedetomidine increased astrocyte expression of BDNF through an extracellular signal-regulated kinase-dependent pathway, inducing subsequent neuroprotective effects.
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http://dx.doi.org/10.1097/ALN.0b013e318286cf36DOI Listing
May 2013

Invasive fungal disease in PICU: epidemiology and risk factors.

Ann Intensive Care 2012 Feb 22;2(1). Epub 2012 Feb 22.

Pediatric and Neonatal Intensive Care Unit, The Children's' Hospital of Bordeaux, Place Amélie Raba Léon, 33076 Bordeaux Cedex, France.

Candida and Aspergillus spp. are the most common agents responsible for invasive fungal infections in children. They are associated with a high mortality and morbidity rate as well as high health care costs. An important increase in their incidence has been observed during the past two decades. In infants and children, invasive candidiasis is five times more frequent than invasive aspergillosis. Candida sp. represents the third most common agent found in healthcare-associated bloodstream infections in children. Invasive aspergillosis is more often associated with hematological malignancies and solid tumors. Recommendations concerning prophylactic treatment for invasive aspergillosis have been recently published by the Infectious Diseases Society of America. Candida albicans is the main Candida sp. associated with invasive candidiasis in children, even if a strong trend toward the emergence of Candida non-albicans has been observed. The epidemiology and the risk factors for invasive fungal infections are quite different if considering previously healthy children hospitalized in the pediatric intensive care unit, or children with a malignancy or a severe hematological disease (leukemia). In children, the mortality rate for invasive aspergillosis is 2.5 to 3.5 higher than for invasive candidiasis (respectively 70% vs. 20% and 30%).
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http://dx.doi.org/10.1186/2110-5820-2-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306204PMC
February 2012

Cranial ultrasonography and transfontanellar Doppler in premature neonates (24-32 weeks of gestation): dynamic evolution and association with a severe adverse neurological outcome at hospital discharge in the Aquitaine cohort, 2003-2005.

Eur J Radiol 2012 Sep 9;81(9):2396-402. Epub 2012 Jan 9.

CHU de Bordeaux, Unité de soins intensifs néonatale et pédiatrique, F-33000 Bordeaux, France.

Objective: To correlate the short-term neurological outcome of early cerebral abnormalities using cranial ultrasonography (US) in premature newborns at their hospital discharge.

Methods: Each newborn born <33 weeks of gestational age (GA) included in a prospective cohort benefited of 3 US: two early in the first week of life (D3 and D8) and one later (Months 1-2) standardized US pulsed Doppler. A US abnormality was ≥one morphologic abnormality (moderate: intra-ventricular hemorrhage (IVH) grades 1-2; severe: IVH 3-4, periventricular leukomalacia, persistent flares). Correlates of having a severe adverse neurological outcome were analyzed using a stepwise backward logistic regression adjusted model with gestational age, early cerebral abnormality at Days 3-8, velocity and with variables with correlation probabilities with p<0.25 in the univariate analysis among occurring co-morbidity events previously defined. Two adjusted logistic regression analyses were conducted including or not velocity data because of missing information.

Results: Among 452 premature included, 11.3% did not have an early US, 74.8% had a normal early US, 13.9% ≥one early morphological US abnormality (10.0% moderate, 3.9% severe). At hospital discharge, 40% were still alive with a normal late US, 33% alive with ≥one late morphological US abnormality (10% moderate, 23% severe), and 10% died. Adjusted correlates of a late US severe abnormality or a neurological related death at hospital discharge were: early US abnormality (aOR: 8.7, 95% CI: 2.3-33.6), GA<29 weeks (aOR: 2.8 95% CI: 1.4-5.4).

Conclusion: This study shows that early US morphological abnormalities increase significantly when the GA decreases and is highly predictive of the occurrence of a further late US severe abnormality or neurological related death at hospital discharge.
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http://dx.doi.org/10.1016/j.ejrad.2011.11.017DOI Listing
September 2012

Patent ductus arteriosus in the preterm infant: a survey of clinical practices in French neonatal intensive care units.

Pediatr Cardiol 2011 Jun 1;32(5):607-14. Epub 2011 Mar 1.

Neonatal and Pediatric Intensive Care Unit, Bordeaux Teaching Hospital, 33076 Bordeaux Cedex, France.

Patent ductus arteriosus (PDA) is one of the most common problems in the care of premature infants, especially the extremely premature. There is no real consensus regarding the diagnostic criteria or treatment of a hemodynamically significant PDA. Its diagnosis, assessment, and treatment still remain challenges. Therefore, we investigated clinical practices in French tertiary neonatology centers regarding the management of PDA to compare their similarities and differences. We sent a questionnaire by email to the PDA specialist in every French tertiary neonatal intensive care unit. It contained 27 items regarding the unit's structure, method of diagnosing PDA, and treatment choices. The completed questionnaire were returned via email and analyzed blindly. The questionnaire response rate was 87.5%, which allowed us to draw some conclusions regarding French clinical practices in the care of neonates with PDA. Although the diagnostic criteria are quite similar, the therapeutic practices are rather different across neonatal care units. We highlight the great variability in French clinical practices when it comes to treating PDA and underscore the necessity for harmonization of these practices, which could be achieved using multicenter, randomized studies to identify the advantages of one approach compared with another.
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http://dx.doi.org/10.1007/s00246-011-9925-8DOI Listing
June 2011

Severe transient ADAMTS13 deficiency in pneumococcal-associated hemolytic uremic syndrome.

Pediatr Nephrol 2011 Apr 15;26(4):631-5. Epub 2010 Dec 15.

Service de Pédiatrie, Hôpital Pellegrin-Enfants, Centre Hospitalier Universitaire, Bordeaux, France.

Thrombotic microangiopathies comprise different entities, including hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and several other conditions. TTP is characterized by hemolytic anemia, thrombocytopenia, and multiorgan failure. TTP is the result of severe von Willebrand factor multimer cleaving protease (ADAMTS13) deficiency that is either inherited or the result of acquired autoantibodies. We report a critically ill 2-year-old girl with invasive pneumococcal disease associated HUS (p-HUS) whose condition was complicated by severe ADAMTS13 deficiency, without detectable inhibitor, in a context of multiple organ failure. The patient recovered with supportive treatment, and ADAMTS13 activity normalized without plasmatherapy. Severe ADAMTS13 deficiency appears to be a manifestation of transient endothelial cell injury in the context of severe sepsis, including invasive p-HUS. The choice of appropriate therapy should not be based on this finding.
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http://dx.doi.org/10.1007/s00467-010-1721-9DOI Listing
April 2011

Paroxysmal extreme pain disorder: a molecular lesion of peripheral neurons.

Nat Rev Neurol 2011 Jan 16;7(1):51-5. Epub 2010 Nov 16.

Yale University Neuroscience and Regeneration Research Center, VA Connecticut Healthcare System, 950 Campbell Avenue, Building 34, West Haven, CT 06516, USA.

Background: a 3-month-old male infant presented, beginning on the second day of life, with paroxysmal painful events that started with tonic contraction of the whole body followed by erythematous harlequin-type color changes.

Investigations: screening of the SCN9A gene, which encodes the voltage-gated sodium channel Na(V)1.7, identified a new mutation, Gly1607Arg, located within the domain IV S4 voltage sensor. Whole-cell patch-clamp analysis demonstrated functional effects of the mutant channel that included impaired inactivation-a hallmark of paroxysmal extreme pain disorder (PEPD).

Diagnosis: the patient was diagnosed as having PEPD, an autosomal dominant disorder characterized by severe rectal pain triggered by defecation or perineal stimulation, usually followed by ocular or submaxillary pain. Erythematous flushing, sometimes in a harlequin pattern, can be a prominent feature of this condition.

Management: treatment with carbamazepine (10 mg/kg/day) for approximately 3 months was ineffective in this case, and the parents made a decision to discontinue the drug. The mother was instructed to avoid painful stimuli that could trigger an episode.
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http://dx.doi.org/10.1038/nrneurol.2010.162DOI Listing
January 2011

Successful treatment with rituximab for acute refractory thrombotic thrombocytopenic purpura related to acquired ADAMTS13 deficiency: a pediatric report and literature review.

Pediatr Crit Care Med 2011 Mar;12(2):e90-3

Service de Pédiatrie Hôpital Pellegrin-Enfants, CHU de Bordeaux and Université de Bordeaux, Bordeaux, France.

Objective: To report the case of a child with severe autoimmune thrombotic thrombocytopenic purpura (TTP) resistant to plasma exchange and steroids who was successfully treated with rituximab.

Design: Case report and review of the literature on pediatric acquired TTP. The report was approved by an independent local ethics committee.

Setting: Pediatric intensive care unit in a tertiary care children's hospital.

Patient: A 10-yr-old boy was referred to the emergency unit with fever, vomiting, confusion, hemolytic anemia, thrombocytopenia, and mild acute renal failure. An atypical hemolytic uremic syndrome was suspected, and plasma exchange was started urgently. The patient was refractory to plasma therapy and presented critical complications. After a diagnosis of acquired TTP attributable to anti-ADAMTS13 autoantibodies had been made, he was treated with rituximab, which resulted in a stable clinical remission.

Interventions: Rituximab therapy.

Measurements And Main Results: Clinical remission.

Conclusions: TTP is a rare but life-threatening condition in children that is characterized by hemolytic anemia, thrombocytopenia, and signs of ischemic organ dysfunction. If renal involvement is present, TTP may be misdiagnosed as hemolytic uremic syndrome, but reliable screening for ADAMTS13 activity and anti-ADAMTS autoantibodies allow us to distinguish the two entities and provide adequate therapy.
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http://dx.doi.org/10.1097/PCC.0b013e3181e89f8fDOI Listing
March 2011

Short-term effect of erythropoietin on brain lesions and aquaporin-4 expression in a hypoxic-ischemic neonatal rat model assessed by magnetic resonance diffusion weighted imaging and immunohistochemistry.

Pediatr Res 2010 Aug;68(2):123-7

Neonatal Intensive Care Unit, University Children's Hospital, Bordeaux 33076, France.

Erythropoietin (Epo) is an endogenous cytokine that regulates hematopoiesis and is widely used to treat anemia. In addition, it has recently increased interest in the neurosciences since the new concept of Epo as a neuroprotective agent has emerged. The potential protective effect of human recombinant Epo (r-hu-Epo) on a hypoxic-ischemic (HI) pup rat model was studied. Cerebral HI was obtained by permanent left carotid artery ligature of pups followed by a 2-h hypoxia. Three hours after carotid occlusion, brain lesions were assessed by magnetic resonance diffusion weighted imaging. Intraperitoneal administration of r-hu-Epo (30,000 U/kg dose) limited both the HI-induced brain lesion area and the decrease in apparent diffusion coefficient (ADC) in the lesion. To identify potential mechanisms underlying the effects of Epo, immunohistochemical detection of caspase-3 and water channel protein aquaporin-4 (AQP4) were performed. No early apoptosis was detected, but up-regulation of AQP4 expression was observed in HI pups that received r-hu-Epo compared with HI animals without treatment. This study demonstrates an early neuroprotective effect of Epo with regard to brain lesion area and ADC values. One possible mechanism of Epo for decreasing brain edema and cellular swelling could be a better clearance of water excess in brain tissue, a process possibly mediated by AQP4.
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http://dx.doi.org/10.1203/PDR.0b013e3181e67d02DOI Listing
August 2010

Sonography-guided positioning of intravenous long lines in neonates.

Eur J Radiol 2010 Jun 15;74(3):e18-21. Epub 2009 Apr 15.

Neonatal and Pediatric Intensive Care Unit, Children's Hospital, Bordeaux, France.

Objective: In neonates, proper positioning of the tip of intravenous long lines (LL) is essential in order to prevent potential life-threatening complications. The gold standard for the evaluation of LL position in neonates is the chest X-ray with or without contrast. We performed a prospective study to assess the use of transthoracic ultrasonography (US) for the positioning of LL in neonates and to compare it to plain radiography.

Materials And Method: Thirty-six consecutive neonates requiring percutaneous LL over a period of 3 months were included in the study. Immediately after LL insertion, the position of its tip was verified using transthoracic US, followed by plain radiography. The two techniques were compared in terms of adequate placement and length of time between insertion and radiographic evaluation of the correct position.

Results: The correlation between positioning by US and plain radiography was very good (r=0.97, r(2)=0.94, p<0.0001). The time needed to verify LL placement by US was shorter by a mean 15 min compared to plain radiography.

Conclusion: US can accurately guide LL tip positioning. We believe that because of the potential gain of time it offers and its lack of ionising radiation, it to be considered as an interesting tool for the positioning of LL in neonates. Yet more accurate results could be obtained with a better-trained staff.
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http://dx.doi.org/10.1016/j.ejrad.2009.03.017DOI Listing
June 2010

Prevalence of anti-varicella-zoster virus antibodies in French infants under 15 months of age.

Clin Vaccine Immunol 2009 Apr 28;16(4):484-7. Epub 2009 Jan 28.

Hôpital Charles Nicolle, Pôle Mère-Femme-Enfant, Centre Hospitalier Universitaire Rouen, France.

Varicella is a widespread disease of childhood resulting from primary infection with varicella-zoster virus (VZV). The objective of this study was to determine the kinetics of the decline of maternal anti-VZV antibodies in French infants between birth and the age of 15 months in order to estimate the duration of passively acquired maternal anti-VZV immunoglobulin G (IgG). This prospective multicenter study was conducted between October 2005 and January 2007 in the pediatric wards and/or pediatric emergency units of seven French hospitals scattered throughout the country. The level of anti-VZV IgG antibodies in serum was measured by a time-resolved fluorescence immunoassay (TRFIA) (the threshold considered positive is 150 mIU/ml). A total of 345 infants were included. Seventy-seven percent of mothers reported a history of varicella. A rapid decline in the prevalence of anti-VZV antibodies was observed during the first few months of life, with the mean antibody titer decreasing from 536 mIU/ml at birth and through 1 month to below the 150-mIU/ml threshold at 3 to 4 months. The half-life of passively acquired maternal immunoglobulins was around 6 weeks. Based on a large number of subjects, this study clearly demonstrated, for the first time in France, high levels of passively acquired maternal antibodies during the neonatal period, and it allowed us to estimate the duration of passively acquired maternal anti-VZV IgG in French infants. After 4 to 5 months, infants had very low levels of maternal anti-VZV IgG, below the 150-mIU/ml cutoff of the VZV IgG TRFIA.
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http://dx.doi.org/10.1128/CVI.00397-08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668269PMC
April 2009

Kinetics of decline of maternal measles virus-neutralizing antibodies in sera of infants in France in 2006.

Clin Vaccine Immunol 2008 Dec 24;15(12):1845-50. Epub 2008 Sep 24.

CHU Brest, Brest, France.

The optimal age for measles vaccination is an important health issue, since maternal antibodies may neutralize the vaccine antigen before a specific immune response develops, while delaying vaccination may increase the risk of complicated diseases in infants. However, measles vaccination impacts the duration of protection afforded by transplacental transfer of maternal antibodies: vaccination-induced maternal antibodies disappear faster than disease-induced antibodies. In order to maintain protection against measles in infants, it is important to monitor the dynamics of this phenomenon in vaccinated populations. To assess the current situation in France, a multicenter, prospective seroepidemiological study was conducted in seven French hospitals between October 2005 and January 2007. Maternal measles antibody concentrations from 348 infants 0 to 15 months old were measured using the plaque reduction neutralization assay. Geometric mean concentrations and the percentage of infants with maternal measles antibody concentrations above the protection threshold (>or=120 mIU/ml) were assessed according to age. Results show that after more than 20 years of routine measles vaccination in France, maternal measles-neutralizing antibodies decrease dramatically in French infants by 6 months of age, from 1,740 mIU/ml for infants 0 to 1 month old to 223 mIU/ml for infants 5 to 6 months old, and that 90% of infants are not protected against measles after 6 months of age. Infant protection against measles could be optimized both by increasing herd immunity through an increased vaccine coverage and by lowering the age of routine vaccination from 12 to 9 months.
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http://dx.doi.org/10.1128/CVI.00229-08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593172PMC
December 2008