Brenda Niu

Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids

SCOPE The cathelicidin antimicrobial peptide (CAMP) gene is induced by 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3), lithocholic acid, curcumin, nicotinamide, and butyrate. Discovering additional small molecules that regulate its expression will identify new molecular mechanisms involved in CAMP regulation and increase understanding of how diet and nutrition can improve immune function. METHODS AND RESULTS We discovered that two stilbenoids, resveratrol and pterostilbene, induced CAMP promoter-luciferase expression. Synergistic activation was observed when either stilbenoid was combined with 1α,25(OH)2 D3. Both stilbenoids increased CAMP mRNA and protein levels in the monocyte cell line U937 and synergy was observed in both U937 and the keratinocyte cell line, HaCaT. Inhibition of resveratrol targets sirtuin-1, cyclic AMP production and the c-Jun N-terminal, phosphoinositide 3 and AMP-activated kinases did not block induction of CAMP by resveratrol or synergy with 1α,25(OH)2 D3. Nevertheless, inhibition of the extracellular signal regulated 1/2 and p38 mitogen-activated protein kinases, increased CAMP gene expression in combination with 1α,25(OH)2 D3 suggesting that inhibition of these kinases by resveratrol may explain, in part, its synergy with vitamin D. CONCLUSION Our findings demonstrate for the first time that stilbenoid compounds may have the potential to boost the innate immune response by increasing CAMP gene expression, particularly in combination with 1α,25(OH)2 D3.

What is the optimal gestational age for women with gestational diabetes type A1 to deliver

OBJECTIVE Type A1 gestational diabetes mellitus (A1GDM), also known as diet-controlled gestational diabetes, is associated with an increase in adverse perinatal outcomes such as macrosomia and Erb palsy. However, it remains unclear when to deliver these women because optimal timing of delivery requires balancing neonatal morbidities from early term delivery against the risk of intrauterine fetal demise (IUFD). We sought to determine the optimal gestational age (GA) for women with A1GDM to deliver. STUDY DESIGN A decision-analytic model was built to compare the outcomes of delivery at 37-41 weeks in a theoretical cohort of 100,000 women with A1GDM. Strategies involving expectant management until a later GA accounted for probabilities of spontaneous delivery, indicated delivery, and IUFD during each week. GA-associated risks of neonatal complications included cerebral palsy, infant death, and Erb palsy. Probabilities were derived from the literature, and total quality-adjusted life years were calculated. Sensitivity analyses were used to investigate the robustness of the baseline assumptions. RESULTS Our model showed that induction at 38 weeks maximized quality-adjusted life years. Within our cohort, delivery at 38 weeks would prevent 48 stillbirths but lead to 12 more infant deaths compared to 39 weeks. Sensitivity analysis revealed that 38 weeks remains the optimal timing of delivery until IUFD rates fall <0.3-fold of our baseline assumption, at which point expectant management until 39 weeks is optimal. CONCLUSION By weighing the risks of IUFD against infant deaths and neonatal morbidities from early term delivery, we determined that the ideal GA for women with A1GDM to deliver is 38 weeks.

Adding Azithromycin to Cephalosporin for Cesarean Delivery Infection Prophylaxis: A Cost-Effectiveness Analysis

OBJECTIVE To investigate the cost-effectiveness of adding azithromycin to standard cephalosporin regimens of cesarean delivery prophylaxis by considering the maternal outcomes in the current and potential subsequent pregnancies. METHODS A cost-effectiveness model was created using TreeAge to compare the outcomes of using azithromycin-cephalosporin with cephalosporin alone in a theoretical cohort of 700,000 women, the approximate number of nonelective cesarean deliveries annually in the United States that occur during labor or after membrane rupture. Outcomes examined included endometritis, wound infection, sepsis, venous thromboembolism, and maternal death in the current pregnancy and uterine rupture, cesarean hysterectomy, and maternal death in subsequent pregnancies, including cost and quality-adjusted life-years for both pregnancies. Probabilities, utilities, and costs were derived from the literature, and a cost-effectiveness threshold was set at

Cost-Effectiveness of Pre-Pregnancy Bariatric Surgery [9C]

100,000 per quality-adjusted life-year. Sensitivity analyses were used to determine the robustness of our results. RESULTS Compared with cephalosporin alone for prophylaxis, our model showed 16,100 fewer cases of endometritis, 17 fewer cases of sepsis, eight fewer cases of venous thromboembolism, and one fewer maternal death with azithromycin-cephalosporin. Additionally, this strategy prevented 36 uterine ruptures and four cesarean hysterectomies in the subsequent pregnancy. Overall, the addition of azithromycin led to both lower costs and higher quality-adjusted life-years when compared with standard cephalosporin prophylaxis. In sensitivity analysis, we found that as long as the cost of azithromycin remained below

Optimal Timing of Delivery in Obese Women: A Decision Analysis

930 (baseline cost

922: Home versus hospital management for vasa previa - a cost-effectiveness analysis

27), it was cost-effective. CONCLUSION For women who undergo cesarean delivery in labor or after membrane rupture, compared with cephalosporin alone, the addition of azithromycin to cesarean delivery infection prophylaxis is less costly and leads to better maternal outcomes in the index delivery and subsequent deliveries. These findings support the use of prophylactic azithromycin at the time of cesarean delivery.

An Extra Hour: Maternal Outcomes With Longer Expectant Management of Second Stage of Labor [15C]

INTRODUCTION: We sought to determine if bariatric surgery is a cost-effective pre-pregnancy approach to reduce pregnancy complications in obese women. METHODS: We assessed the cost-effectiveness of bariatric surgery prior to becoming pregnant in a theoretical cohort of obese women age 20–39 in the United States. Outcomes included gestational diabetes (GDM), preeclampsia, preterm delivery, cesarean delivery, maternal mortality, and neurodevelopmental disability. All model inputs were derived from the literature. We calculated quality-adjusted life years (QALYs) to compare strategies, accounting for maternal and neonatal utilities. We ran our models with and without consideration of anovulation rates given its substantial impact on QALYs. RESULTS: Pre-pregnancy bariatric surgery led to lower rates of GDM, preeclampsia, and large-for-gestational-age infants, but more small-for-gestational-age (SGA) infants. Overall, no bariatric surgery was the preferred strategy with lower costs and better outcomes. However, when considering the impact on fecundity from improved ovulation rates after bariatric surgery, it would then become cost effective at

140: Timing of delivery for women with gestational diabetes type A1 (A1GDM): A cost-effectiveness analysis

2,528 per QALY. Women who underwent pre-pregnancy bariatric surgery had higher rates of preterm delivery, SGA infants, cesarean delivery, maternal death and neonates with neurodevelopmental disabilities. Univariate sensitivity analyses showed that pre-pregnancy bariatric surgery became the preferred strategy when the probability of having an SGA baby became less than 0.121 from a baseline probability of 0.156. CONCLUSION: Bariatric surgery reduces the risk of GDM, preeclampsia and LGA infants, but it is not a cost-effective intervention in obese women of reproductive age. However, in women who are anovulatory, it may be a reasonable approach to improve overall pregnancy outcomes.