Epidemiology and outcomes of ventilator-associated events in critically ill children: Evaluation of three different definitions.

OBJECTIVE: Ventilator-associated pneumonia (VAP) is one of the most common healthcare-associated infections in pediatric intensive care units (PICUs), but its definite diagnosis remains controversial. The CDC Ventilator-Associated Event (VAE) module (validated in adults) constitutes a new approach for VAP surveillance. DESIGN: We described epidemiological characteristics of PICU VAE cases, investigated possible risk factors, and evaluated 3 different sets of diagnostic VAE criteria. SETTING: This study was conducted in a PICU in a tertiary-care general hospital in northern Greece during 2017-2019. PATIENTS: The study included patients aged 35 days-16 years who received mechanical ventilation. METHODS: From medical records, we retrieved epidemiological data, clinical data, and laboratory characteristics as well as ventilator settings for our analysis. We assessed "oxygen deterioration" for the tier 1 CDC VAE module using 3 sets of diagnostic criteria: (1) CDC adult VAE criteria [increase of daily minimum fraction of inspired oxygen (FiO2) ≥ 0.2 or positive end expiratory pressure (PEEP) ≥ 3 cmH2O for 2 days], (2) the US pediatric VAE criteria [increase of FiO2 ≥ 0.25 or mean airway pressure (MAP) ≥ 4 cmH2O for 2 days], and (3) the European pediatric VAE criteria (increase of FiO2 ≥ 0.2 or PEEP ≥ 2 cmH2O for 1 day or increase of FiO2 ≥ 0.15 and PEEP ≥ 1 cm H2O for 1 day). RESULTS: Among 326 children admitted to the PICU, 301 received mechanical ventilation. The incidence rate according to the CDC adult VAE criteria was 4.7 per 1,000 ventilator days. For the US pediatric VAE criteria the incidence rate was 6 per 1,000 ventilator days. For the European pediatric VAE criteria the incidence rate was 9.7 per 1,000 ventilator days. These results revealed statistically significant correlation of all 3 algorithms with adverse outcomes, including mortality. CONCLUSIONS: All VAE algorithms were associated with higher mortality rates. Our findings highlight the need for a unified pediatric VAE definition to improve preventive strategies.

Functional characterization of novel loss-of-function mutations in the vasopressin type 2 receptor gene causing nephrogenic diabetes insipidus.

BACKGROUND: X-linked nephrogenic diabetes insipidus (NDI) is a rare polyuric disorder caused by inactivating mutations in the arginine vasopressin receptor Type 2 (AVPR2) gene. METHODS: NDI patients from six unrelated families were subjected to mutational analysis of the AVPR2 gene. In-depth in vitro characterization of novel AVPR2 mutants by a combination of functional and immunological techniques provided further insight into molecular mechanisms causing receptor dysfunction. RESULTS: Mutational analysis revealed four novel (A89P, G107R, Q174R, W208X) and three recurrent (V277A, R337X, ΔR247-G250) mutations within the AVPR2 gene. One family carried the missense mutation R337X and a 12-bp deletion (ΔR247-G250), corresponding to a fragment in the third intracellular loop (ICL3), which was not genetically linked to R337X. The functionally tested missense mutations A89P, G107R and Q174R led to reduced receptor cell surface expression in transfected COS-7 cells, most probably due to misfolding and intracellular retention, and consequently to reduction or loss of agonist-mediated cyclic adenosine monophosphate formation. Deletion of R247-G250 had no effect on receptor function in vitro. Comparison with other mammalian AVPR2 orthologs showed that this part of the ICL3 is structurally not conserved and, therefore, less relevant for receptor function. In contrast, all missense mutations (A89P, G107R, Q174R, V277A) affect receptor positions that were fully preserved during mammalian evolution. CONCLUSION: Our results provide valuable information about residues critical for AVPR2 folding, trafficking and function and proof that these mutations are responsible for causing NDI in the affected subjects.

Branched chain amino acids as adjunctive therapy to ketogenic diet in epilepsy: pilot study and hypothesis.

A pilot prospective follow-up study of the role of the branched chain amino acids as additional therapy to the ketogenic diet was carried out in 17 children, aged between 2 and 7 years, with refractory epilepsy. All of these patients were on the ketogenic diet; none of them was seizure free, while only 13 had more or less benefited from the diet. The addition of branched chain amino acids induced a 100% seizure reduction in 3 patients, while a 50% to 90% reduction was noticed in 5. Moreover, in all of the patients, no reduction in ketosis was recorded despite the change in the fat-to-protein ratio from 4:1 to 2.5:1. Although our data are preliminary, we suggest that branched chain amino acids may increase the effectiveness of the ketogenic diet and the diet could be more easily tolerated by the patients because of the change in the ratio of fat to protein.