Selecting the best ventilator hyperinflation technique based on physiologic markers: A randomized controlled crossover study.

BACKGROUND: Ventilator hyperinflation (VHI) is effective in improving respiratory mechanics, secretion removal, and gas exchange in mechanically ventilated subjects; however, there are no recommendations for the best ventilator settings to perform the technique. OBJECTIVE: To compare six modes of VHI, concerning physiological markers of efficacy and safety criteria to support the selection of optimal settings. METHODS: Thirty mechanically ventilated patients underwent six modes of VHI in a randomized order. The delivered volume, expiratory flow bias criteria, overdistension, patient-ventilator asynchronies and hemodynamic variables were assessed during the interventions. RESULTS: Volume-controlled ventilation with inspiratory flow of 20 lpm (VC-CMV20) and pressure support ventilation (PSV) achieved the best effectiveness scores (P < 0.05). The target peak pressure of 40 cmH2O was associated with a high incidence of overdistension. PSV showed a lower incidence of patient-ventilator asynchronies. CONCLUSIONS: The modes VC-CMV20 and PSV are the most effective for VHI. Alveolar overdistension and patient-ventilator asynchronies must be considered when applying VHI.

Dual molecular diagnosis contributes to atypical Prader-Willi phenotype in monozygotic twins.

We describe monozygotic twin girls with genetic variation at two separate loci resulting in a blended phenotype of Prader-Willi syndrome and Pitt-Hopkins syndrome. These girls were diagnosed in early infancy with Prader-Willi syndrome, but developed an atypical phenotype, with apparent intellectual deficiency and lack of obesity. Array-comparative genomic hybridization confirmed a de novo paternal deletion of the 15q11.2q13 region and exome sequencing identified a second mutational event in both girls, which was a novel variant c.145+1G>A affecting a TCF4 canonical splicing site inherited from the mosaic mother. RNA studies showed that the variant abolished the donor splicing site, which was accompanied by activation of an alternative non-canonical splicing-site which then predicts a premature stop codon in the following exon. Clinical re-evaluation of the twins indicated that both variants are likely contributing to the more severe phenotypic presentation. Our data show that atypical clinical presentations may actually be the expression of blended clinical phenotypes arising from independent pathogenic events at two loci.