Nitric oxide metabolism in the human placenta during aberrant maternal inflammation.

KEY POINTS: Nitric oxide (NO) is a gasotransmitter with important physiological and pathophysiological roles in pregnancy. There is limited information available about the sources and metabolism of NO and its bioactive metabolites (NOx) in both normal and complicated pregnancies. The present study characterized and quantified endogenous NOx in human and mouse placenta following determination of the stability of exogenous NOx in placental homogenates. NOx have differential stability in placental homogenates. NO and iron nitrosyl species (FeNOs), are relatively unstable in placental homogenates from normal placentas. Exogenous NO, nitrite and nitrosothiols react with placental homogenates to form iron nitrosyl complexes. FeNOs were also detected endogenously in mouse and human placenta. NOx levels in placental villous tissue are increased in fetal growth restriction vs. placentas from women with normal pregnancies, particularly in fetal growth restriction associated with pre-eclampsia. Villitis was not associated, however, with an increase in NOx levels in either normotensive or pre-eclamptic placentas. The results call for further investigation of FeNOs in normal and complicated pregnancies. ABSTRACT: Nitric oxide (NO) is a gasotransmitter with important roles in pregnancy under both physiological and pathophysiological conditions. Although products of NO metabolism (NOx) also have significant bioactivity, little is known about the role of NO and NOx under conditions of aberrant placental inflammation during pregnancy. An ozone-based chemiluminescence approach was used to investigate the stability and metabolic fate of NOx in human placental homogenates from uncomplicated pregnancies in healthy mothers compared to that in placental tissue from normotensive and pre-eclamptic pregnancies complicated with fetal growth restriction (FGR) with and without villitis of unknown aetiology. We hypothesized that placental NOx would be increased in FGR vs. normal tissue, and be further increased in villitis vs. non-villitis placentas. Findings indicate that nitrate, nitrite and nitrosothiols, but not NO or iron nitrosyl species (FeNOs), are relatively stable in placental homogenates from normal placentas, and that NO, nitrite and nitrosothiols react with placental homogenates to form iron nitrosyl complexes. Furthermore, NOx levels in placental villous tissue are increased in FGR vs. placentas from women with normal pregnancies, particularly in FGR associated with pre-eclampsia. However, in contrast to our hypothesis, villitis was not associated with an increase in NOx levels in either normotensive or pre-eclamptic placentas. Our results also strongly support the involvement of FeNOs in both mouse and human placenta, and call for their further study as a critical mechanistic link between pre-eclampsia and fetal growth restriction.

Effects of patient navigation on satisfaction with cancer care: a systematic review and meta-analysis.

PURPOSE: Patient navigation (PN) is a model of healthcare coordination designed to reduce barriers to achieving optimal health outcomes. Systematic reviews evaluating whether PN is associated with higher patient satisfaction with cancer care are lacking. METHODS: We conducted a systematic review to synthesize evidence of comparative studies evaluating the effectiveness of PN programs to improve satisfaction with cancer-related care. We included studies reported in English that: (1) evaluated a PN intervention designed to increase satisfaction with cancer care; and (2) involved a randomized controlled trial (RCT) or non-RCT approach. Standardized forms were used to abstract data from studies. These data were evaluated for methodological quality, summarized qualitatively, and synthesized under a random effects model. RESULTS: The initial search yielded 831 citations. Nine met inclusion criteria. Five had adequate data (1 RCT and 4 non-RCTs) to include in the meta-analysis. Methodological quality of included studies ranged from weak to strong, with half rated as weak. Findings of the RCTs showed a statistically significant increase in satisfaction with cancer care involving PN (standardized mean difference (SMD) = 2.30; 95% confidence interval 1.79, 2.80, p < 0.001). Pooled results from non-RCTs showed no significant association between PN and satisfaction with cancer-related care (standardized mean difference = 0.39; 95% confidence interval - 0.02, 0.80, p = 0.06). CONCLUSIONS: Although PN has been widely implemented to improve cancer care, high-quality studies are needed to characterize the relationship between PN and satisfaction with cancer-related care.