Use of High-Frequency Ventilation in the Pediatric Intensive Care Unit.

Objective To evaluate the clinical characteristics, ventilator settings, and gas exchange indices of patients placed on high-frequency percussive ventilation (HFPV) and high-frequency oscillatory ventilation (HFOV). Methods Retrospective observation of all consecutive patients aged 0 to 18 years with acute respiratory failure managed with high-frequency ventilation from the institution's introduction of HFPV on May 1, 2012, until July 10, 2013. Measurements and Main Results Twenty-seven patients underwent HFPV as a first mode of high-frequency ventilation and 16 patients underwent HFOV first. HFPV was used more frequently in patients with acute respiratory illnesses (p < 0.01), lower Pediatric Index of Mortality 2 scores (rank-sum p < 0.04), higher Spo 2/Fio 2 (SF) ratios (p < 0.01), and lower oxygen saturation indices (p < 0.01). HFPV patients showed increased SF ratios (p < 0.01) and decreased Paco 2 levels (p = 0.02) 6 hours after initiation, and HFOV patients showed no significant differences. Peak inspiratory pressures (HFPV) and mean airway pressures (HFOV) remained at or below 30 cm H2O at each time point. HFPV and HFOV patients had an average of 2.8 and 2.9 mode changes, respectively. Mortality was 15% in the HFPV group and 50% in the HFOV group. Conclusions HFPV is associated with rapid improvement in oxygenation and ventilation at acceptable airway pressures in patients with acute respiratory failure of various etiologies, primarily for those with difficulties of ventilation or secretion management. In our institution, HFOV appears to be initiated first in children with higher severity of illness.

Orally available and efficacious α4ß1/α4ß7 integrin inhibitors.

A series of potent α4ß1/α4ß7 integrin inhibitors is reported, including an inhibitor 12d with remarkable oral exposure and efficacy in rat models of rheumatoid arthritis and Crohn's disease.

Arylsulfonamide pyrimidines as VLA-4 antagonists.

A series of (S)-2-(2-(diethylamino)-5-(N-alkyl-N-sulfonamido)pyrimidin-4-ylamino)-3-(4-(carbamoyloxy)phenyl)propanoic acid is discovered as orally available VLA-4 antagonists. Representative compounds 11b and 11p showed efficacy in multiple in vivo animal models. The in vitro selectivity of 11p is also described.