The long-term outcome of hepatic artery thrombosis after liver transplantation in children: role of urgent revascularization.

Hepatic artery thrombosis (HAT), one of the most severe complications of pediatric orthotopic liver transplantation (OLT), often compromises graft and/or child survival. Of 590 OLT performed in 516 children over a 20-year period, 45 were complicated by early HAT, during the first 2 weeks after transplantation. Systematic Doppler ultrasonographic detection of HAT allowed successful surgical revascularization in 19 instances, resulting in a 20-year graft survival rate of 77% versus 24% of cases when revascularization was not attempted or failed. A combination of surgical emergency revascularization, biliary interventional radiology, biliary surgery and/or retransplantation resulted in an 80% 20-year patient survival rate, identical to that of transplanted children who did not experience early HAT. The majority of long-term survivors with their initial graft had normal liver tests, no biliary dilation on ultrasonography and minimal or moderate fibrosis on liver histology. A failed attempt at revascularization did not significantly alter patient survival. Despite these encouraging results, for the children and their parents to overcome the entire process in terms of reoperations, repeated radiological interventions, number of hospitalizations and emotional stress, remains an ordeal of such magnitude that it justifies renewed efforts to progress in the prevention of this complication.

Febrile brain stroke and tuberculous meningitis: persisting threat in non-endemic countries.

Tuberculous meningitis is uncommon in western countries and its outcome is poor when it is not diagnosed and treated in good time. Here, we present a case of febrile brain stroke revealing a tuberculous arachnoiditis in a 13-month-old infant living in a non-endemic country. Thanks to prompt specific antibiotherapy, the clinical outcome was globally favourable in spite of the occurrence of an asymptomatic brain tuberculoma, which disappeared spontaneously. Although tuberculous meningitis is rare in non-endemic countries, it must be evoked in strokes occurring in a febrile context.

Two silent substitutions in the PDHA1 gene cause exon 5 skipping by disruption of a putative exonic splicing enhancer.

BACKGROUND: Synonymous mutations within exons may cause aberrant splicing by disrupting exonic splicing enhancer (ESE) motifs in the vicinity of non consensus splice sites. Mutational analysis of PDHA1 revealed only one silent single nucleotide substitution in exon 5 in two unrelated boys and a girl (c.483C>T and c.498C>T variants, respectively). For both patients, pyruvate dehydrogenase complex activity was low and the immunoreactive E1alpha protein was defective in cultured fibroblasts. METHODS AND RESULTS: One of the boys was a somatic mosaic for the c.483C>T variant, as shown by the variable ratio of mutant to normal alleles in fibroblast, lymphocyte and single hair root DNA. Transcript analysis in fibroblasts from the three patients revealed the presence of both normal and truncated cDNAs, with the splicing out of exon 5 predicted to result in a frame shift and premature termination (p.Arg141AlafsX11). The treatment of fibroblasts with emetine before harvesting to prevent nonsense mRNA-mediated decay increased the amount of mutant mRNA. In silico analysis revealed that each variant disrupted a putative SRp55 binding site and that the intron 5 donor splice site (5'ss) contained a weak splicing signal. Transient transfection of COS-7 or Hela cells with hybrid minigene constructs containing wild-type or mutant PDHA1 exon 5, followed by RT-PCR demonstrated that each variant resulted in the incomplete inclusion of PDHA1 exon 5, and that this defect was corrected following the restoration of a perfect consensus sequence for the 5' splice site by site-directed mutagenesis. CONCLUSION: These two synonymous mutations expand the spectrum of rare PDHA1 splicing mutations, all of which are located in non canonical splice sites.

[Effects of nasal continuous positive airway pressure ventilation in infants with severe acute bronchiolitis]. / Place de la ventilation non invasive nasale dans la prise en charge des broncho-alvéolites sévères.

OBJECTIVE: Usefulness of nasal continuous positive airway pressure (NCPAP) in severe acute bronchiolitis has been checked. The objective of this descriptive study was to evaluate the feasibility, safety and risk factors of NCPAP failure. POPULATION AND METHODS: One hundred and forty-five infants were hospitalised in our intensive care unit during the 2 last epidemics (2003-2004, 2004-2005). Among them, 121 needed a respiratory support, either invasive ventilation (N=68) or NCPAP (N=53). RESULTS: General characteristics were similar during the 2 periods. Percentage of NCPAP failure, defined by tracheal intubation requirement during the stay in paediatric intensive care unit, was quite similar during the 2 periods (25%), but number of NCPAP increased twofold. Whatever the evolution was in the NCPAP group, we observed a significant decrease in respiratory rate (60+/-16 vs 47.5+/-13.7 cycle/min., P<0.001) and PaCO2 (64.3+/-13.8 vs 52.6+/-11.7 mmHg, P=0.001) during NCPAP. Only PRISM calculated at day 1 and initial reduction of PaCO2 were predictive of NCPAP failure. Percentage of ventilator associated pneumonia was similar (22%) between the invasive ventilation group and infants who where intubated because of failure of NCPAP. Duration of respiratory support and stay were reduced in the NCPAP group (P<0.002). CONCLUSION: NCPAP appears to be a safe alternative to immediate intubation in infants with severe bronchiolitis.

[Bronchiolitis treated with mechanical ventilation: prognosis factors and outcome in a series of 135 children]. / Bronchiolites en unité de réanimation pédiatrique: facteurs pronostiques et devenir respiratoire des nourrissons ventilés.

UNLABELLED: Viral bronchiolitis is usually associated with favorable outcome as regard to mortality. Only few studies reported severe bronchiolitis requiring mechanical ventilation, and respiratory outcome is not well described. METHODS: Therefore, we conducted a retrospective study in a series of 135 children admitted in a single Pediatric Intensive Care Unit (PICU) over a four year period (1994-1998). All of them were admitted for viral bronchiolitis requiring mechanical ventilation. RESULTS: At admission, 83% of them were less than three months old. Prematurity at birth was present in 33,3%. Mortality was observed in four cases (2,9%), all premature babies with mechanical ventilation at birth. Univariate analysis showed as main factors associated to mortality: prematurity (P =0,056) and acute respiratory distress syndrome (P =0,017). Childhood asthma was observed in 40,4% of children without any associated factor wether at birth or in PICU related to such outcome. CONCLUSION: Bronchiolitis associated with mechanical ventilation is particularly observed in very young babies and prematurity is the main factor associated to mortality. Mechanical ventilation seems not to be associated with unfavorable respiratory outcome. Considering physiology and population, non invasive ventilation could be an effective alternative of mechanical ventilation.

Severe cardiac failure in newborns with VGAM. Prognosis significance of hemodynamic parameters in neonates presenting with severe heart failure owing to vein of Galen arteriovenous malformation.

OBJECTIVE: Neonatal vein of Galen malformation complicated by severe cardiac failure is a rare disease. The purpose was to assess the outcome of this life-threatening malformation and identify hemodynamic prognostic factors. DESIGN: Retrospective study. PATIENTS: Twenty-four newborns with cardiac failure requiring mechanical ventilation were consecutively admitted from 1986 to 2000. INTERVENTIONS: Cardiovascular evaluation including echocardiogram was performed in all cases. Eighteen transarterial shunt occlusions with glue were applied by the same team of three physicians. MEASUREMENTS AND RESULTS: Twelve babies survived and underwent one endovascular session at least (median age 20 days) with a mean 63 months follow-up. Embolization was not performed in 6 of the 12 nonsurvivors because of severe brain damage or profound hypotension Cardiogenic shock occurred in all nonsurvivors, but also in one long-term survivor (p<0.0001). Echocardiogram showed signs of right ventricular failure, most often in the dead babies (p=0.005). The pulmonary systemic arterial pressure ratio was significantly higher in the nonsurvivor group (p=0.031), and it decreased significantly after the first embolization only in patients who survived (p=0.01). Patent ductus arteriosus and a diastolic aortic reversed-flow were present in all nonsurvivors in contrast to 30% of the long-term survivors (p=0.003 ). There was no difference in the left ventricular contractility and mean cardiac output between the two groups. CONCLUSIONS: The outcome of vein of Galen malformation complicated by severe cardiac failure requiring mechanical ventilation remains poor. Neonatal embolization seems to be beneficial only in babies without suprasystemic pulmonary hypertension.

[Severe Reye syndrome: report of 14 cases managed in a pediatric intensive care unit over 11 years]. / Syndrome de Reye sévère: à propos de 14 cas pris en charge dans une unité de réanimation pédiatrique pendant 11 ans.

UNLABELLED: Idiopathic Reye syndrome is a rare disease revealed by unexplained encephalopathy and microvesicular liver steatosis. Some clinical and epidemiological studies mainly performed in English speaking countries questioned the reality of Reye syndrome because numerous know inherited metabolic diseases, and some of them unrecognized, could mimick this disorder. We focused in our study on severe forms of Reye syndrome admitted to a pediatric intensive care unit. METHODS: Retrospective study over the last eleven years (1991-2001) included all the pediatric patients admitted to our tertiary referral center with the classical American Reye syndrome criteria (e.g. CDC). Extensive metabolic screening was performed in all cases, except for the ultimately dead patients. RESULT: Fourteen patients (mean age 52 months) were included. Fever always occurred before their admission and aspirin (n = 12) or acetaminophen (n = 7) was prescribed. Median Glasgow scale was 7 on admission. Mean amoniac plasma level was 320 mumol/L and alanine-aminotransferase peak plasma level 1475 +/- 1387 IU/L. Mechanical ventilation was started in ten children and six of them underwent continuous venovenous hemofiltration. Three patients ultimately died and 11 survived with a mean five years follow-up without relapses or neurological impairment. Any of them demonstrated inherited metabolic disease except for one infant with hereditary fructose intolerance. CONCLUSION: Unlike widespread opinion, severe Reye syndrome without identified metabolic disorders seems to not disappear in our country. Reye syndrome remains a potentially life threatening disease and raises for aggressive treatment of brain edema. If aspirin and Reye syndrome association are not formally documented in France, cautiousness must be kept in mind and all the aspirin adverse effects notifications should be addressed to the public drugs survey network.

Cerebral venous thrombosis after embolization of pediatric AVM with jugular bulb stenosis or occlusion: management and prevention.

PURPOSE: Thrombosis of cerebral arteriovenous malformation after embolization is rare, but can involve the normal venous network with extensive venous thrombosis. We report angioarchitecture findings, our management and prevention strategy for this complication in pediatric AVMs. METHODS: In this 5.5-year retrospective series, we reviewed records of 13 patients under 15 years who were anticoagulated after embolization. In our initial experience 4 children who didn't receive any prophylactic anticoagulation presented with extensive venous thrombosis after embolization (group 1). Following this, nine children with similar angioarchitecture and embolization modalities were treated with prophylactic anticoagulation immediately after embolization (group 2). We analyzed the type of AVM, angioarchitecture, dose of prophylactic anticoagulant, efficacy/complications of treatment and late outcome. RESULTS: All patients in group 1 had severe jugular bulb stenosis/occlusion associated with cerebral venous dilatation. In group 2 with similar angioarchitecture, only three patients (33%) developed extensive thrombosis. In both groups, thrombosis occurred within two days of treatment in six children and two weeks in one child. The diagnosis was suspected on intracranial hypertension in five patients and occulomotor disorder in one. One was asymptomatic. All children were treated with therapeutic doses of LMWH (anti-Xa: 0.5-1). No hemorrhagic complications occurred. Good venous remodeling was observed in all but one patient. CONCLUSION: Anticoagulation in extensive venous thrombosis after AVM embolization in children appears to be safe and effective. In cases with angioarchitectural features of dilatation of the cerebral venous network and occlusion/severe stenosis of the jugular bulbs, full dose anticoagulation may be required to prevent thrombosis.

[Medical care of brain malformative vascular diseases discovered during the pre- or neonatal period]. / Prise en charge des malformations vasculaires cérébrales découvertes en période ante- ou néonatale.

Three types of brain arteriovenous vascular malformations can be found during the neonatal period, according to their anatomical location. Vein of Galen malformations are the most common. The others are pial arteriovenous malformations or dural arteriovenous malformations, which include dural sinus malformations. They can be asymptomatic, but most often they are associated with different symptoms, related to their angioarchitecture or their effect on the brain. High-flow arteriovenous malformations can thus be responsible for heart failure. Local or regional venous hyperpressure exposes the patient to subacute or chronic brain lesions, or to hydrovenous disorders such as hydrocephalus. Some types of venous reflux can expose patients to brain hemorrhage. The treatment chosen for these vascular malformations and their consequences is transarterial or transvenous embolization, depending on the angioarchitecture and type of lesion. The schedule for the treatment will be determined according to the malformation type and its local or general effects on the brain. The aim of this article is to present the recommendations of the French National Referral Center for neurovascular malformations in children, in order to help clinicians and radiologists treat these patients during pre- or neonatal period.

[Necrotizing community-acquired Staphylococcus aureus pneumonia]. / Pneumopathie aiguë nécrosante à Staphylocoque doré sécréteur de la toxine de Panton-Valentine.

Acute necrotizing pneumonia due to Panton-Valentine secreting Staphylococcus aureus was identified as a clinical entity by Gilet et al., in 2002. This severe acute necrotizing pneumonia occurring in previously healthy children and adolescents can lead to a rapid fatal outcome even if quickly diagnosed and treated. We report the case of a healthy 10-year-old girl presenting with hemorrhagic necrotizing pneumonia and septic shock. Bacteriological cultures yielded methicillin-susceptible Staphylococcus aureus. The course of the disease was characterized by recurrent uncontrolled hemoptysia leading to refractory hypoxemia. The details of the hospital stay are presented. We discuss the clinical features of the disease and describe recent epidemiologic data and Panton-Valentine toxin research results as well as primary hospital care and treatment.

Neurological toxicity of acyclovir: report of a case in a six-month-old liver transplant recipient.

Acyclovir-induced neurotoxicity is a rare adverse effect, found especially in adults with pre-existing renal failure. We report a case of neurotoxicity of acyclovir in a six-month-old liver transplant recipient. Case report and review of literature are discussed.