Évolution de la qualité de vie après un traumatisme crânien par accident de la route : un suivi à cinq ans de la cohorte ESPARR

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Type I Interferon in Children with Viral or Bacterial Infections.

BACKGROUND: Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians' decisions and limit antibiotic overuse. METHODS: Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. RESULTS: Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P 0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). CONCLUSIONS: IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov (NCT03163628)

Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition

PURPOSE: Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and neonatal intensive care (ESPNIC) experts' definition of paediatric RSS. METHODS: We conducted a two-round Delphi study followed by an observational multicentre retrospective study. One hundred and fourteen paediatric intensivists answered a clinical case-based, two-round Delphi survey, identifying clinical items consistent with RSS. Multivariate analysis of these items in a development single-centre cohort (70 patients, 30 % mortality) facilitated development of RSS definitions based on either a bedside or computed severity score. Both scores were subsequently tested in a validation cohort (six centres, 424 patients, 11.6 % mortality). RESULTS: From the Delphi process, the draft definition included evidence of myocardial dysfunction and high blood lactate levels despite high vasopressor treatment. When assessed in the development population, each item was independently associated with the need for extracorporeal life support (ECLS) or death. Resultant bedside and computed septic shock scores had high discriminative power against the need for ECLS or death, with areas under the receiver operating characteristics curve of 0.920 (95 % CI 0.89-0.94), and 0.956 (95 % CI 0.93-0.97), respectively. RSS defined by a bedside score equal to or higher than 2 and a computed score equal to or higher than 3.5 was associated with a significant increase in mortality. CONCLUSIONS: This ESPNIC definition of RSS accurately identifies children with the most severe form of septic shock

Translational gap in pediatric septic shock management: an ESPNIC perspective

Background: The Surviving Sepsis Campaign and the American College of Critical Care Medicine guidelines have provided recommendations for the management of pediatric septic shock patients. We conducted a survey among the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) members to assess variations to these recommendations. Methods: A total of 114 pediatric intensive care physicians completed an electronic survey. The survey consisted of four standardized clinical cases exploring seven clinical scenarios. Results: Among the seven diferent clinical scenarios, the types of fuids were preferentially non-synthetic colloids (albumin) and crystalloids (isotonic saline) and volume expansion was not limited to 60 ml/kg. Early intubation for mechanical ventilation was used by 70% of the participants. Norepinephrine was stated to be used in 94% of the PICU physicians surveyed, although dopamine or epinephrine is recommended as frst-line vasopressors in pediatric septic shock. When norepinephrine was used, the addition of another inotrope was frequent. Specifc drugs such as vasopressin or enoximone were used in <20%. Extracorporeal life support was used or considered by 91% of the physicians audited in certain specifc situations, whereas the use of high-fow hemofltration was considered for 44%. Conclusions: This pediatric septic shock management survey outlined variability in the current clinician-reported practice of pediatric septic shock management. As most recommendations are not supported by evidence, these fndings outline some limitation of existing pediatric guidelines in regard to context and patient’s specifcity

Thigh Ultrasound Monitoring Identifies Decreases in Quadriceps Femoris Thickness as a Frequent Observation in Critically Ill Children.

OBJECTIVES: Significant muscle wasting develops in critically ill adults, with subsequent worse outcomes. In the pediatric setting, occurrence and effects of muscle wasting are undescribed; this is in part due to a lack of validated, objective methods for assessing muscle wasting. A single measurement of quadriceps femoris thickness has failed to show consistent reproducibility. We hypothesized that averaging repeated measurements could afford good reproducibility to allow for quadriceps femoris thickness decline detection and monitoring. DESIGN: A prospective bedside observational study. SETTING: Two PICUs. PATIENTS: Mechanically ventilated critically ill children were 15 years and younger. INTERVENTIONS: Transverse and longitudinal axis measurements of quadriceps femoris anterior thickness were undertaken using bedside ultrasound. The average of four measurement values was recorded. The location of measurement was marked for consistency within subsequent measurements by the same or another trained operator, to assess intra- and interoperator repeatability and reproducibility of the technique. Where feasible, serial measurements were undertaken until the time of extubation in a group of children with prolonged PICU stay (> 5 d). MEASUREMENTS AND MAIN RESULTS: Seventy-three children were enrolled to assess intra- and interoperator ultrasound reliability. Their median (25-75 interquartile range) age and weight were 30 months (4.5-96) and 10 kg (5-23.5). In the intraoperator repeatability study, mean relative difference in quadriceps femoris muscle thickness was 0.36% ± 2.5% (lower and upper limits of agreement: -4.5/+5.2%). In the interoperator reproducibility study, intraclass correlation coefficient was 0.998. In the 17 children monitored over their PICU stay, quadriceps femoris thickness significantly decreased at day 5 by 9.8% (p = 0.006) and by 13.3% (< 0.001) at the last performed measurement. CONCLUSIONS: Quadriceps femoris thickness decrease, proposed as a surrogate for muscle mass, is an early, frequent, and intense phenomenon in PICU. Quadriceps femoris ultrasonography is a reliable technique to monitor this process and in future could help to guide rehabilitation and nutrition interventions.The study was founded by ALLP (Association Lyonnaise de Logistique posthospitalière) 2015 grant. FVV has received consultant honoraria from Nutricia and Baxter and grants from Baxter, Nestle, Institut Aguettant, ALLP and Fresenius Kabi. For the remaining authors none were declared

Noninvasive positive pressure ventilation for acute respiratory failure in children: a concise review

Noninvasive positive pressure ventilation (NPPV) refers to the delivery of mechanical respiratory support without the use of endotracheal intubation (ETI). The present review focused on the effectiveness of NPPV in children > 1 month of age with acute respiratory failure (ARF) due to different conditions. ARF is the most common cause of cardiac arrest in children. Therefore, prompt recognition and treatment of pediatric patients with pending respiratory failure can be lifesaving. Mechanical respiratory support is a critical intervention in many cases of ARF. In recent years, NPPV has been proposed as a valuable alternative to invasive mechanical ventilation (IMV) in this acute setting. Recent physiological studies have demonstrated beneficial effects of NPPV in children with ARF. Several pediatric clinical studies, the majority of which were noncontrolled or case series and of small size, have suggested the effectiveness of NPPV in the treatment of ARF due to acute airway (upper or lower) obstruction or certain primary parenchymal lung disease, and in specific circumstances, such as postoperative or postextubation ARF, immunocompromised patients with ARF, or as a means to facilitate extubation. NPPV was well tolerated with rare major complications and was associated with improved gas exchange, decreased work of breathing, and ETI avoidance in 22-100% of patients. High FiO2 needs or high PaCO2 level on admission or within the first hours after starting NPPV appeared to be the best independent predictive factors for the NPPV failure in children with ARF. However, many important issues, such as the identification of the patient, the right time for NPPV application, and the appropriate setting, are still lacking. Further randomized, controlled trials that address these issues in children with ARF are recommended

Knock Down of Heat Shock Protein 27 (HspB1) Induces Degradation of Several Putative Client Proteins

Hsp27 belongs to the heat shock protein family and displays chaperone properties in stress conditions by holding unfolded polypeptides, hence avoiding their inclination to aggregate. Hsp27 is often referenced as an anti-cancer therapeutic target, but apart from its well-described ability to interfere with different stresses and apoptotic processes, its role in non-stressed conditions is still not well defined. In the present study we report that three polypeptides (histone deacetylase HDAC6, transcription factor STAT2 and procaspase-3) were degraded in human cancerous cells displaying genetically decreased levels of Hsp27. In addition, these proteins interacted with Hsp27 complexes of different native size. Altogether, these findings suggest that HDAC6, STAT2 and procaspase-3 are client proteins of Hsp27. Hence, in non stressed cancerous cells, the structural organization of Hsp27 appears to be a key parameter in the regulation by this chaperone of the level of specific polypeptides through client-chaperone type of interactions

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2