Immunomodulatory Activity of the Tyrosine Kinase Inhibitor Dasatinib to Elicit NK Cytotoxicity against Cancer, HIV Infection and Aging.

Tyrosine kinase inhibitors (TKIs) have been extensively used as a treatment for chronic myeloid leukemia (CML). Dasatinib is a broad-spectrum TKI with off-target effects that give it an immunomodulatory capacity resulting in increased innate immune responses against cancerous cells and viral infected cells. Several studies reported that dasatinib expanded memory-like natural killer (NK) cells and γδ T cells that have been related with increased control of CML after treatment withdrawal. In the HIV infection setting, these innate cells are associated with virus control and protection, suggesting that dasatinib could have a potential role in improving both the CML and HIV outcomes. Moreover, dasatinib could also directly induce apoptosis of senescence cells, being a new potential senolytic drug. Here, we review in depth the current knowledge of virological and immunogenetic factors associated with the development of powerful cytotoxic responses associated with this drug. Besides, we will discuss the potential therapeutic role against CML, HIV infection and aging.

Impact of intertwin interval on short-term neonatal outcomes of the second twin in dichorionic pregnancies with vaginal delivery.

OBJECTIVE: To examine the effect of intertwin interval on umbilical cord pH and Apgar scores of the second twin after vaginal delivery. METHODS: A retrospective study of twin deliveries at a university hospital in Spain between August 2012 and September 2017. Inclusion criteria were vaginal delivery of both twins at 32 gestational weeks or more. Exclusion criteria were monochorionic pregnancies and indication for cesarean delivery. The sample was dichotomized by intertwin interval (<10 and ≥10 minutes). Neonatal outcomes including Apgar scores and umbilical cord pH were evaluated. RESULTS: Overall, 323 twin deliveries were included. Intertwin interval was less than 10 minutes in 277 (85.6%) cases, and 10 minutes or longer in 46 (14.2%). There were no differences in maternal or obstetric characteristics between the groups. Incidence of instrumental delivery (P<0.001) and internal podalic version (P<0.001) for the second twin was higher in the longer interval group. A longer interval was associated with higher frequencies of 1-minute Apgar score below 4 (P=0.009), 5-minute Apgar score below 7 (P<0.001), and umbilical cord pH below 7.15 (P<0.001). CONCLUSION: Second twins with an intertwin interval of 10 minutes or longer are more likely to have poorer Apgar scores and arterial blood pH below 7.15.