David Longchamp

Severe viral respiratory infections in children with IFIH1 loss-of-function mutations

Significance Life-threatening susceptibility to common respiratory infections in previously healthy children can be indicative of pathogen-specific primary immunodeficiencies due to rare deleterious variants in key genes and pathways of the immune system. These findings have implications for prevention and treatment of susceptible children. Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome sequencing, we identified and characterized three rare loss-of-function variants in IFIH1, which encodes an RIG-I-like receptor involved in the sensing of viral RNA. Functional testing of the variants IFIH1 alleles demonstrated that the resulting proteins are unable to induce IFN-β, are intrinsically less stable than wild-type IFIH1, and lack ATPase activity. In vitro assays showed that IFIH1 effectively restricts replication of human respiratory syncytial virus and rhinoviruses. We conclude that IFIH1 deficiency causes a primary immunodeficiency manifested in extreme susceptibility to common respiratory RNA viruses.

Performance of Predictive Equations Specifically Developed to Estimate Resting Energy Expenditure in Ventilated Critically Ill Children

Objective To determine, based on indirect calorimetry measurements, the biases of predictive equations specifically developed recently for estimating resting energy expenditure (REE) in ventilated critically ill children, or developed for healthy populations but used in critically ill children. Study design A secondary analysis study was performed using our data on REE measured in a previous prospective study on protein and energy needs in pediatric intensive care unit. We included 75 ventilated critically ill children (median age, 21 months) in whom 407 indirect calorimetry measurements were performed. Fifteen predictive equations were used to estimate REE: the equations of White, Meyer, Mehta, Schofield, Henry, the World Health Organization, Fleisch, and Harris‐Benedict and the tables of Talbot. Their differential and proportional biases (with 95% CIs) were computed and the bias plotted in graphs. The Bland‐Altman method was also used. Results Most equations underestimated and overestimated REE between 200 and 1000 kcal/day. The equations of Mehta, Schofield, and Henry and the tables of Talbot had a bias ≤10%, but the 95% CI was large and contained values by far beyond ±10% for low REE values. Other specific equations for critically ill children had even wider biases. Conclusions In ventilated critically ill children, none of the predictive equations tested met the performance criteria for the entire range of REE between 200 and 1000 kcal/day. Even the equations with the smallest bias may entail a risk of underfeeding or overfeeding, especially in the youngest children. Indirect calorimetry measurement must be preferred.

Estimation of Resting Energy Expenditure Using Predictive Equations in Critically Ill Children: Results of a Systematic Review.

Provision of adequate energy intake to critically ill children is associated with improved prognosis, but resting energy expenditure (REE) is rarely determined by indirect calorimetry (IC) due to practical constraints. Some studies have tested the validity of various predictive equations that are routinely used for this purpose, but no systematic evaluation has been made. Therefore, we performed a systematic review of the literature to assess predictive equations of REE in critically ill children. We systematically searched the literature for eligible studies, and then we extracted data and assigned a quality grade to each article according to guidelines of the Academy of Nutrition and Dietetics. Accuracy was defined as the percentage of predicted REE values to fall within ±10% or ±15% of the measured energy expenditure (MEE) values, computed based on individual participant data. Of the 993 identified studies, 22 studies testing 21 equations using 2326 IC measurements in 1102 children were included in this review. Only 6 equations were evaluated by at least 3 studies in critically ill children. No equation predicted REE within ±10% of MEE in >50% of observations. The Harris-Benedict equation overestimated REE in two-thirds of patients, whereas the Schofield equations and Talbot tables predicted REE within ±15% of MEE in approximately 50% of observations. In summary, the Schofield equations and Talbot tables were the least inaccurate of the predictive equations. We conclude that a new validated indirect calorimeter is urgently needed in the critically ill pediatric population.).

Endoscopic treatment of post-supraglottoplasty stenosis

Supraglottic stenosis (SPGS) after supraglottoplasty (SGP) for laryngomalacia (LM) is rare, has debilitating consequences in very small patients, and there is no clear mention of its treatment in the current literature. We describe our technique of treating SPGS using the CO2 laser and endoscopic suturing aimed at achieving maximum mucosalisation of the supraglottis. Additional epiglottopexy using Lichtenbergers needle carrier is important to prevent backward tilt of the epiglottis during healing process. Our modification of the laser-assisted SGP technique would lower the chances of developing this complication. This article is protected by copyright. All rights reserved.

Meningococcal serogroup W135 epiglottitis in an adolescent patient

Acute epiglottitis is a severe and potentially life-threatening condition. Since the implementation of Haemophilus influenzae vaccination, the number of cases of epiglottitis has decreased and the proportion of other infectious causes has increased. We report a case of acute epiglottitis in a teenager caused by Neisseria meningitidis, an unusual pathogen.

Improvement in perioperative care in pediatric cardiac surgery by shifting the primary focus of treatment from cardiac output to perfusion pressure: Are beta stimulants still needed?

OBJECTIVE An important aspect of perioperative care in pediatric cardiac surgery is maintenance of optimal hemodynamic status using vasoactive/inotropic agents. Conventionally, this has focused on maintenance of cardiac output rather than perfusion pressure. However, this approach has been abandoned in our center in favor of one focusing primarily on perfusion pressure, which is presented here and compared to the conventional approach. DESIGN A retrospective study. SETTING Regional center for congenital heart disease. University Hospital of Lausanne, Switzerland. PATIENTS All patients with Aristotle risk score ≥8 that underwent surgery from 1996 to 2012 were included. Patients operated between 1996 and 2005 (Group 1: 206 patients) were treated according to the conventional approach. Patients operated between 2006 and 2012 (Group 2: 217 patients) were treated according to our new approach. INTERVENTIONS All patients had undergone surgery for correction or palliation of congenital cardiac defects. OUTCOME MEASUREMENTS Mortality, duration of ventilation and inotropic treatment, use of ECMO, and complications of poor peripheral perfusion (need for hemofiltration, laparotomy for enterocolitis, amputation). RESULTS The two groups were similar in age and complexity. Mortality was lower in group 2 (7.3% in group 1 vs 1.4% in group 2, P < .005). Ventilation times (hours) and number of days on inotropic/vasoactive treatment (all agents), expressed as median and interquartile range [Q1-Q3] were shorter in group 2: 69 [24-163] hours in group 1 vs 35 [22-120] hours in group 2 (P < .01) for ventilation, and 9 [3-5] days in group 1 vs 7 [2-5] days in group 2 (P < .05) for inotropic/vasoactive agents. There were no differences in ECMO usage or complications of peripheral perfusion. CONCLUSIONS Results in pediatric cardiac surgery may be improved by shifting the primary focus of perioperative care from cardiac output to perfusion pressure.