Search

Objective: The objective of this study was to assess the relationship of prenatal diagnosis of critical congenital heart disease (CHD) to preoperative and postoperative patient findings. Method: Retrospective analysis of neonates with critical CHD who underwent cardiothoracic surgery at one of four centers in North Carolina between 2008-2013. Surgical data collected by sites for submission to the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) and the North Carolina CHD Lifespan Database were queried. Results: There were 715 patients with STS records; 566 linked to the NC CHD database. Patients with prenatal diagnosis had a lower incidence of preoperative risk factors, including need for mechanical ventilation and presence of shock. However, prenatally diagnosed patients had worse short-term outcomes, including higher operative mortality, higher incidence of select postoperative complications, and longer LOS. There was no difference in one-year mortality. Conclusion: Our findings are consistent with current literature which suggests that prenatal diagnosis of critical CHD is associated with a more optimized preoperative clinical status. However, we found that patients with prenatal diagnoses had less favorable postoperative outcomes. This needs to be investigated further, but may be secondary to patient-specific factors, such as CHD disease severity.

Clinical trials of the first approved integrase inhibitor (INI), raltegravir, have demonstrated a drop in the human immunodeficiency virus type 1 (HIV-1) RNA loads of infected patients that was unexpectedly more rapid than that with a potent reverse transcriptase inhibitor, and apparently dose independent. These clinical outcomes are not understood. In tissue culture, although their inhibition of integration is well documented, the effects of INIs on levels of unintegrated HIV-1 cDNAs have been variable. Furthermore, there has been no report to date on an INI's effect on these episomal species in vivo. Here, we show that prophylactic treatment of transgenic rats with the strand transfer INI GSK501015 reduced levels of viral integrants in the spleen by up to 99.7%. Episomal two-long-terminal-repeat (LTR) circles accumulated up to sevenfold in this secondary lymphoid organ, and this inversely correlated with the impact on the proviral burden. Contrasting raltegravir's dose-ranging study with HIV patients, titration of GSK501015 in HIV-infected animals demonstrated dependence of the INI's antiviral effect on its serum concentration. Furthermore, the in vivo 50% effective concentration calculated from these data best matched GSK501015's in vitro potency when serum protein binding was accounted for. Collectively, this study demonstrates a titratable, antipodal impact of an INI on integrated and episomal HIV-1 cDNAs in vivo. Based on these findings and known biological characteristics of viral episomes, we discuss how integrase inhibition may result in additional indirect antiviral effects that contribute to more rapid HIV-1 decay in HIV/AIDS patients.