Vitamin K and ECMO for neonatal hypoxic respiratory failure.

INTRODUCTION: The objectives of this retrospective cohort study were to examine the effect of vitamin K administration on hemorrhagic and thrombotic complications, blood product utilization, and outcomes in neonatal extracorporeal membrane oxygenation (ECMO). METHODS: In the pilot study, complications, blood product use, and outcome data for neonates who received (n = 21) or did not receive (n = 18) a single dose of vitamin K (5 mg) immediately after initiation of ECMO for respiratory failure between 2006 and 2010 were compared. In the validation cohort, complications and outcomes were compared for 74 consecutive neonates supported with ECMO for respiratory failure who received (n = 45) or did not receive (n = 29) additional vitamin K once daily for prothrombin time (PT) ⩾14 seconds during ECMO from 2014 to 2019. RESULTS: In the pilot study, vitamin K at ECMO initiation was associated with fewer thrombotic complications and similar hemorrhagic complications. The volume of fresh frozen plasma was higher in neonates who received vitamin K, but total blood product and other component volume did not differ between groups. ECMO run time, survival off ECMO, survival to discharge, and length of stay did not differ between cohorts. In the validation cohort, neonates who received additional vitamin K during ECMO had longer ECMO run time and length of stay, but no difference in mortality was observed. Further, thrombotic and hemorrhagic complications as well as blood product exposure were similar between cohorts. CONCLUSIONS: These data suggest that routine vitamin K administration may have limited or no benefit during neonatal ECMO.

Academic performance in moderately and late preterm children in the United States: are they catching up?

OBJECTIVE: To determine whether preterm birth of 32-36 6/7 weeks gestation affected school performance from kindergarten through fifth grade. STUDY DESIGN: We assessed 14350 term infants and 1195 32-36 6/7 weeks gestation infants followed in the Early Childhood Longitudinal Study Kindergarten 2011 cohort for classroom performance in kindergarten-fifth grade. Multivariable regression was performed for comparisons, and data were weighted to be representative of the US population. RESULTS: Children born 35-36 6/7 weeks gestation had no significant difference in their academic scores or performance, while 32-34 6/7 weeks' children had lower academic scores and teacher performance scores when compared to term children. Children born between 32 and 36 6/7 weeks gestation had higher odds of individualized education plan needs and had learning disability diagnoses compared to term children. CONCLUSIONS: Children born between 32 and 34 6/7 weeks gestation have poor school performance compared to term children. Children born between 32 and 36 6/7 weeks gestation are at risk for learning disabilities and likely benefit from continued support and services to improve achievement throughout school.

Testing models of the APC tumor suppressor/ß-catenin interaction reshapes our view of the destruction complex in Wnt signaling.

The Wnt pathway is a conserved signal transduction pathway that contributes to normal development and adult homeostasis, but is also misregulated in human diseases such as cancer. The tumor suppressor adenomatous polyposis coli (APC) is an essential negative regulator of Wnt signaling inactivated in >80% of colorectal cancers. APC participates in a multiprotein "destruction complex" that targets the proto-oncogene ß-catenin for ubiquitin-mediated proteolysis; however, the mechanistic role of APC in the destruction complex remains unknown. Several models of APC function have recently been proposed, many of which have emphasized the importance of phosphorylation of high-affinity ß-catenin-binding sites [20-amino-acid repeats (20Rs)] on APC. Here we test these models by generating a Drosophila APC2 mutant lacking all ß-catenin-binding 20Rs and performing functional studies in human colon cancer cell lines and Drosophila embryos. Our results are inconsistent with current models, as we find that ß-catenin binding to the 20Rs of APC is not required for destruction complex activity. In addition, we generate an APC2 mutant lacking all ß-catenin-binding sites (including the 15Rs) and find that a direct ß-catenin/APC interaction is also not essential for ß-catenin destruction, although it increases destruction complex efficiency in certain developmental contexts. Overall, our findings support a model whereby ß-catenin-binding sites on APC do not provide a critical mechanistic function per se, but rather dock ß-catenin in the destruction complex to increase the efficiency of ß-catenin destruction. Furthermore, in Drosophila embryos expressing some APC2 mutant transgenes we observe a separation of ß-catenin destruction and Wg/Wnt signaling outputs and suggest that cytoplasmic retention of ß-catenin likely accounts for this difference.