Thomas Baugnon

French experience of 2009 A/H1N1v influenza in pregnant women.

Background The first reports on the pandemic influenza 2009 A/H1N1v from the USA, Mexico, and Australia indicated that this disease was associated with a high mortality in pregnant women. The aim of this study was to describe and compare the characteristics of severe critically ill and non-severe pregnant women with 2009 A/H1N1v-related illness in France. Methodology/Principal Findings A national registry was created to screen pregnant women with laboratory-confirmed 2009 A/H1N1v influenza. Three hundred and fifteen patients from 46 French hospitals were included: 40 patients were admitted to intensive care units (severe outcomes), 111 were hospitalized in obstetric or medical wards (moderate outcomes), and 164 were outpatients (mild outcomes). The 2009 A/H1N1v influenza illness occurred during all pregnancy trimesters, but most women (54%), notably the severe patients (70%), were in the third trimester. Among the severe patients, twenty (50%) underwent mechanical ventilation, and eleven (28%) were treated with extracorporeal membrane oxygenation. Three women died from A/H1N1v influenza. We found a strong association between the development of a severe outcome and both co-existing illnesses (adjusted odds ratio [OR], 5.1; 95% confidence interval [CI], 2.2–11.8) and a delay in oseltamivir treatment after the onset of symptoms (>3 or 5 days) (adjusted OR, 4.8; 95% CI, 1.9–12.1 and 61.2, 95% CI; 14.4–261.3, respectively). Among the 140 deliveries after 22 weeks of gestation known to date, 19 neonates (14%) were admitted to a neonatal intensive care unit, mainly for preterm delivery, and two neonates died. None of these neonates developed 2009 A/H1N1v infection. Conclusions This series confirms the high incidence of complications in pregnant women infected with pandemic A/H1N1v observed in other countries but depicts a lower overall maternal and neonatal mortality and morbidity than indicated in the USA or Australia. Moreover, our data demonstrate the benefit of early oseltamivir treatment in this specific population.

Use of recombinant activated factor VII in intractable bleeding during pediatric neurosurgical procedures.

Objective: To report the use of recombinant activated factor VII (NovoSeven; Novo Nordisk A/S, Bagsvaerd, Denmark) in children undergoing major neurosurgical procedures and experiencing massive uncontrolled hemorrhagic shock. Design: Retrospective review of patients and analysis of clinical and biological effects of an intravenous administration of recombinant activated factor VII. Setting: Neurosurgical anesthesia and critical care unit of a pediatric university hospital. Patients/Subjects: Four children, <12-kg body weight, experiencing life-threatening perioperative hemorrhage required conventional treatment (massive red blood cells, fresh frozen plasma, platelet transfusion, and surgical hemostatic maneuvers) that failed to obtain definite hemostasis. Interventions: Intravenous administration of recombinant activated factor VII (100 &mgr;g/kg). Results: Intravenous administration resulted in a significant decrease in blood loss within minutes (preventing further need of transfusion), normalization of biological hemostasis markers, and improved surgical hemostasis. No side effects of recombinant activated factor VII were noted, and all patients, except one, had a good recovery. Conclusions: These four patients support the use of recombinant activated factor VII as a useful adjunct to control massive life-threatening bleeding during pediatric neurosurgical procedures when other means failed. However, the data are still limited in children, and more extensive research is needed to define the indications of recombinant activated factor VII in massive surgical hemorrhage in low-weight children.

Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial

BACKGROUND Mucopolysaccharidosis type IIIB syndrome (also known as Sanfilippo type B syndrome) is a lysosomal storage disease resulting in progressive deterioration of cognitive acquisition after age 2-4 years. No treatment is available for the neurological manifestations of the disease. We sought to assess the safety and efficacy of a novel intracerebral gene therapy. METHODS Local regulatory authorities in France allowed inclusion of up to four children in this phase 1/2 study. Treatment was 16 intraparenchymal deposits (four in the cerebellum) of a recombinant adenoassociated viral vector serotype 2/5 (rAAV2/5) encoding human α-N-acetylglucosaminidase (NAGLU) plus immunosuppressive therapy. We assessed tolerance, neurocognitive progression, brain growth, NAGLU enzymatic activity in CSF, and specific anti-NAGLU immune response for 30 months after surgery. This trial is registered with EudraCT, number 2012-000856-33, and the International Standard Clinical Trial Registry, number ISRCTN19853672. FINDINGS Of seven eligible children, the four youngest, from France (n=2), Italy (n=1), and Greece (n=1), aged 20, 26, 30, and 53 months, were included between February, 2012, and February, 2014. 125 adverse events were recorded, of which 117 were treatment emergent and included six classified as severe, but no suspected unexpected serious adverse drug reactions were seen. Vector genomes were detected in blood for 2 days after surgery. Compared with the natural history of mucopolysaccharidosis type III syndromes, neurocognitive progression was improved in all patients, with the youngest patient having function close to that in healthy children. Decrease in developmental quotient was -11·0 points in patient one, -23·0 in patient two, -29·0 in patient three, and -17·0 in patient four, compared with -37·7 in the natural history of the disease. NAGLU activity was detected in lumbar CSF and was 15-20% of that in unaffected children. Circulating T lymphocytes that proliferated and produced tumour necrosis factor α upon ex-vivo exposure to NAGLU antigens were detectable at 1-12 months and 3-12 months, respectively, but not at 30 months in three of four patients. INTERPRETATION Intracerebral rAVV2/5 was well tolerated and induced sustained enzyme production in the brain. The initial specific anti-NAGLU immune response that later subsided suggested acquired immunological tolerance. The best results being obtained in the youngest patient implies a potential window of opportunity. Longer follow-up is needed to further assess safety outcomes and persistence of improved cognitive development. FUNDING Association Française Contre les Myopathies, Vaincre les Maladies Lysosomales, Institut Pasteur, and UniQure.

Hemorrhagic shock and encephalopathy syndrome in a quadriplegic child: an argument for the triggering role of impaired thermoregulatory response.

Study Design. A case presentation of hemorrhagic shock and encephalopathy syndrome (HSES). Objective. To describe an unusual complication of uncontrolled fever in a tetraplegic child and to discuss possible pathophysiological mechanisms in these circumstances. Summary of Background Data. HSES is a rare and dramatic disorder of unknown origin occurring mainly in infants and young children. Clinical features of HSES associate hyperpyrexia, acute diarrhea, circulatory collapse, coma, convulsions, and multiple organ failure (MOF). Altered physiologic thermoregulatory response in infants exposed to abruptly increased core temperature or altered thermal environment, and links with heat stroke, have been mentioned in previous publications. Methods. We report a case of HSES occurring in a 6-year-old girl with post-traumatic C4 quadriplegia. She eventually experienced hyperpyrexia, deep shock, watery diarrhea, and severe MOF developed rapidly. Despite rapidly resolving MOF, severe brain lesions consistent with HSES were observed and resulted in permanent neurologic impairment. Results. Negative bacterial and viral screening eliminated a septic origin. In this child, impaired thermoregulatory response to acute hyperpyrexia resulting from complete quadriplegia could be the necessary condition for the development of HSES in the presence of acute hyperpyrexia of unknown origin. Conclusion. Quadriplegic patients, especially young children, could be considered at increased risk of developing severe MOF and acute central nervous system impairment consistent with HSES, when exposed to heat stress and should be treated promptly.

Intraoperative hyponatremia: is it related to surgical procedure or fluid maintenance?

SIR—We read with interest the article by Jagannathan et al. entitled ‘Glossopharyngeal nerve blocks for awake laryngeal mask airway insertion in an infant with Pierre-Robin syndrome: can a Glidescope come to the rescue?’, in which the authors describe performing glossopharyngeal nerve blocks in an infant (1). The authors are to be commended for describing another technique to facilitate airway management in these patients. While this technique for performing glossopharyngeal nerve blocks may be useful in some patients, the available literature suggests that it is unnecessary for this application in infants <2 months old. In their description of awake insertion of the laryngeal mask in five infants with either the Robin sequence or Treacher Collins syndrome, Asai et al. state ‘our patients tolerated the presence of the mask and finger in the mouth without topical anesthesia’ and ‘it appeared they became calm’ (2). In the first description of this technique by Markakis et al. in three infants with micrognathia, the level of distress associated with awake laryngeal mask insertion is described as comparable to that seen with orogastric or nasogastric tube insertion in the awake child. The authors point out that this level of distress did not prevent a smooth inhaled induction of anesthesia (3). In our own review of this technique in 14 infants with the Robin sequence, we found no mention of intolerance of awake laryngeal mask insertion; furthermore, there were no episodes of oxyhemoglobin desaturation prior to or during induction of anesthesia in any of these infants, suggesting satisfactory tolerance (4). Glossopharyngeal nerve injections carry the risks of local anesthetic toxicity and may result in bleeding that can interfere with subsequent intubation attempts. It is quite likely that the level of stimulation caused by positioning the glidescope is comparable to that associated with laryngeal mask placement. We therefore suggest that these nerve blocks be reserved for infants who fail an initial attempt at awake placement of the laryngeal mask. P A U L A. S T R I C K E R J O H N E. F I A D J O E The Children’s Hospital of Philadelphia Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania School of Medicine Philadelphia, PA, USA (email: strickerp@email.chop.edu) References