Clinical characteristics of premature infants who orally feed on continuous positive airway pressure.

BACKGROUND: Between 32 and 34 weeks postconceptional age (PCA), premature infants typically achieve neuromuscular maturation to initiate the coordination of a nutritive suck triad. Many premature infants also require intubation, which has been associated with dysphagia in adults and infants. At our institution, despite these factors, some infants have been noted to tolerate oral feeds while on continuous positive airway pressure (CPAP). AIMS: Compare the clinical characteristics and duration of intubation in infants that initiate oral feedings on CPAP to infants that did not begin oral feeding on CPAP. STUDY DESIGN: Retrospective case control study. SUBJECTS: Infants with gestational age < 32 weeks who required CPAP at 32 weeks PCA. OUTCOME MEASURES: Oral feeding was defined as any oral feed ≥5 ml. Duration of intubation was defined as the number of intubated days prior to 32 weeks PCA. RESULTS: Of the 243 infants on CPAP at 32 weeks PCA, 31% (n = 76) began oral feeding on CPAP. Infants who initiated oral feeding on CPAP were of younger gestational age at birth (median 26 versus 27 weeks, p < 0.001) and remained intubated for longer (median 10.5 versus 2 days, p < 0.001). CONCLUSIONS: Infants who began oral feeding on CPAP had lower gestational age and longer duration of intubation than infants who started oral feeding off CPAP.

Impact of Parental Presence at Infants' Bedside on Neonatal Abstinence Syndrome.

BACKGROUND: Despite increased incidence of neonatal abstinence syndrome (NAS) over the past decade, minimal data exist on benefits of parental presence at the bedside on NAS outcomes. OBJECTIVE: To examine the association between rates of parental presence and NAS outcomes. METHODS: This was a retrospective, single-center cohort study of infants treated pharmacologically for NAS using a rooming-in model of care. Parental presence was documented every 4 hours with nursing cares. We obtained demographic data for mothers and infants and assessed covariates confounding NAS severity and time spent at the bedside. Outcomes included length of stay (LOS) at the hospital, extent of pharmacotherapy, and mean Finnegan withdrawal score. Multiple linear regression modeling assessed the association of parental presence with outcomes. RESULTS: For the 86 mother-infant dyads, the mean parental presence during scoring was on average 54.4% (95% confidence interval [CI], 48.8%-60.7%) of the infant's hospitalization. Maximum (100%) parental presence was associated with a 9 day shorter LOS (r = -0.31; 95% CI, -0.48 to -0.10; P < .01), 8 fewer days of infant opioid therapy (r = -0.34; 95% CI, -0.52 to -0.15; P < .001), and 1 point lower mean Finnegan score (r = -0.35; 95% CI, -0.52 to -0.15; P < .01). After adjusting for breastfeeding, parental presence remained significantly associated with reduced NAS score and opioid treatment days. CONCLUSIONS: More parental time spent at the infant's bedside was associated with decreased NAS severity. This has important implications for clinical practice guidelines for NAS.

Agents that stabilize mutated von Hippel-Lindau (VHL) protein: results of a high-throughput screen to identify compounds that modulate VHL proteostasis.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that affects multiple organs. Treatment is mainly surgical, and effective systemic therapies are needed. We developed a cell-based screening tool to identify compounds that stabilize or upregulate full-length, point-mutated VHL protein. The 786-0 cell line was infected with full-length W117A-mutated VHL linked to a C-terminal Venus fluorescent protein. This VHL-W117A-Venus line was used to screen the Prestwick drug library and was tested against proteasome inhibitors MG132 and bortezomib. Western blot validation and evaluation of functional readouts, including hypoxia-inducible factor 2α (HIF2α) and glucose transporter 1 (Glut1) levels, were performed. We found that bortezomib, MG132, and the Prestwick compounds 8-azaguanine, thiostrepton, and thioguanosine upregulated VHL-W117A-Venus in 786-0 cells. 8-Azaguanine downregulated HIF2α levels and was augmented by the presence of VHL W117A. VHL p30 band intensities varied as a function of compound used, suggesting alternate posttranslational processing. Nuclear-cytoplasmic localization of VHL-W117A-Venus varied among the different compounds. In conclusion, a 786-0 cell line containing VHL-W117A-Venus was successfully used to identify compounds that upregulate VHL levels, with differential effect on VHL intracellular localization and posttranslational processing. Further screening efforts will broaden the number of pharmacophores available to develop therapeutic agents that will upregulate and refunctionalize mutated VHL.