Background: Following cardiac surgery, infants often remain endotracheally intubated upon arrival to the cardiac ICU. High-flow nasal cannula and non-invasive positive pressure ventilation are used to support patients following extubation. There are limited data on the superiority of either mode to prevent extubation failure. Methods: We conducted a single-centre retrospective study for infants (<1 year) and/or <10 kg who underwent cardiac surgery between 3/2019–3/2020. Data included patient and clinical characteristics and operative variables. The study aimed to compare high-flow nasal cannula versus non-invasive positive pressure ventilation following extubation and their association with extubation failure. Secondarily, we examined risk factors associated with extubation failure. Results: There were 424 patients who met inclusion criteria, 320 (75%) were extubated to high-flow nasal cannula, 104 (25%) to non-invasive positive pressure ventilation, and 64 patients (15%) failed extubation. The high-flow nasal cannula group had lower rates of extubation failure (11%, versus 29%, p = 0.001). Infants failing extubation were younger and had higher STAT score (p < 0.05). Compared to high-flow nasal cannula, non-invasive positive pressure ventilation patients were at 3.30 times higher odds of failing extubation after adjusting for patient factors (p < 0.0001). Conclusions: Extubation failure after cardiac surgery occurs in smaller, younger infants, and those with higher risk surgical procedures. Patients extubated to non-invasive positive pressure ventilation had 3.30 higher odds to fail extubation than patients extubated to high-flow nasal cannula. The optimal mode of respiratory support in this patient population is unknown.

To address the growing need for new antimicrobial agents, we explored whether inhibition of bacterial signaling machinery could inhibit bacterial growth. Because bacteria rely on two-component signaling systems to respond to environmental changes, and because these systems are both highly conserved and mediated by histidine kinases, inhibiting histidine kinases may provide broad spectrum antimicrobial activity. The histidine kinase ATP binding domain is conserved with the ATPase domain of eukaryotic Hsp90 molecular chaperones. To find a chemical scaffold for compounds that target histidine kinases, we leveraged this conservation. We screened ATP competitive Hsp90 inhibitors against CckA, an essential histidine kinase in Caulobacter crescentus that controls cell growth, and showed that the diaryl pyrazole is a promising scaffold for histidine kinase inhibition. We synthesized a panel of derivatives and found that they inhibit the histidine kinases C. crescentus CckA and Salmonella PhoQ but not C. crescentus DivJ; and they inhibit bacterial growth in both Gram-negative and Gram-positive bacterial strains.

ObjectiveTo evaluate the performance of a publicly available model predicting extubation success in very preterm infants. Study DesignRetrospective study of infants born < 1250 g at a single center. Model performance evaluated using the area under the receiver operating curve (AUROC) and comparing observed and expected probabilities of extubation success, de ned as survival ≥ 5 d without an endotracheal tube. ResultsOf 177 infants, 120 (68%) were extubated successfully. The median (IQR) gestational age was 27 weeks (25-28) and weight at extubation was 915 g (755-1050). The model had acceptable discrimination (AUROC 0.72 [95% CI 0.65-0.80]) and adequate calibration (calibration slope 0.96, intercept − 0.06, mean observed-to-expected difference in probability of extubation success − 0.08 [95% CI -0.01, -0.15]). ConclusionsThe extubation success prediction model has acceptable performance in an external cohort, supporting its potential utility in clinical decision-making. Additional studies are needed to determine if its use can improve outcomes.74.