Daphne Lacoursiere

Cancer Immunoediting of the NK Group 2D Ligand H60a

Cancer immunoediting describes the process whereby highly immunogenic tumor cells are removed, or edited, from the primary tumor repertoire by the immune system. In immunodeficient mice, the editing process is hampered, and “unedited” tumor cells can be recovered and studied. In this study, we compared unedited and edited tumors for their expression of NK group 2D (NKG2D) ligands, a family of surface proteins expressed on tumor cells that can activate NK cell cytotoxic activity. We found that the expression of the NKG2D ligand H60a was more heterogeneous in groups of unedited 3′-methylcholanthrene sarcoma cell lines compared with that in edited 3′-methylcholanthrene sarcoma cell lines (i.e., some unedited cell lines expressed very high levels of H60a, whereas other unedited and edited cell lines expressed very low levels). We also found that some highly immunogenic cell lines displayed a bimodal distribution consisting of H60a-hi and H60a-lo cells. In one of these cell lines, the H60a-hi cells could be removed by passaging the cells through RAG2−/− mice, resulting in edited cell lines that were poor targets for NK cells and that displayed progressive tumor growth. This editing of H60a-hi cells required NK cells and NKG2D. Our studies show that the expression of H60a on tumors cells can be actively modulated by the immune system, thereby implicating this NKG2D ligand in tumor immunosurveillance.

The association of inadequate mid-pregnancy weight gain and preterm birth in twin pregnancies.

Objective:To determine whether inadequate gestational weight gain in the second trimester in twin pregnancies is associated with an increased risk of preterm birth (PTB) at <32 weeks.Study Design:Retrospective cohort study including 489 twin pregnancies delivered between 2001 and 2013. Rates of weight gain at different gestational ages were compared with Institute of Medicine guidelines.Result:An inadequate rate of weight gain at <20 weeks was not associated with PTB. Patients with inadequate rates of weight gain at 20 to 28 weeks had a higher risk of PTB at <32 weeks (37.6%) compared to those with adequate weight gain (15.2%) (P<0.001). In multivariate analysis, women with inadequate weight gain at 20 to 28 weeks were 2.8 times more likely to deliver at <32 weeks (95% confidence interval 1.65 to 4.81).Conclusion:Inadequate gestational weight gain at 20 to 28 weeks in twin pregnancies was the strongest predictor of PTB at <32 weeks. This represents an optimal time for interventions to improve weight gain and potentially decrease rates of PTB.

The impact of inadequate gestational weight gain in obese diabetic women

Objective:To determine the effect of inadequate gestational weight gain (GWG) on neonatal birth weight in diabetic obese women.Study Design:Retrospective cohort study of women with an initial body mass index (BMI) ⩾30 kg m−2 and gestational or type 2 diabetes was conducted. GWG was stratified: inadequate (<11 lbs), adequate (11 to 20 lbs) or excessive (>20 lbs). The primary outcome was birth weight. Secondary outcomes included hypertensive disorders, gestational age at delivery, mode of delivery and Apgar scores.Result:A total of 211 obese diabetic women were identified. Of those, 37% had inadequate GWG, 25% had adequate GWG and 38% had excessive GWG. Women with inadequate GWG had lower mean birth weights (P=0.048), as well as lower rates of cesarean delivery (P=0.017) and lower rates of pregnancy-related hypertensive disorders (P=0.026) compared with those with adequate and excessive GWG.Conclusion:Inadequate GWG was associated lower mean birth weights, lower rates of cesarean delivery and lower rates of pregnancy-related hypertensive disorders.

Maternal and neonatal outcomes in women with twin pregnancies with excessive gestational weight gain

Abstract Objective: To determine if an excessive rate of gestational weight gain (GWG) in twin pregnancies is associated with adverse obstetric outcomes. Methods: Retrospective cohort study of twin pregnancies delivered at the University of California, San Diego 2001–2014. Women were included if they had adequate or excessive rates of GWG as determined by Institute of Medicine guidelines. Demographic and outcome variables were collected by chart review. Results: Four hundred and eighty-nine twin pregnancies met inclusion criteria. Of which, 40.5% had adequate rates of GWG and 41.5% had excessive rates of GWG. The rates of preterm birth and gestational diabetes were similar between the two groups. Gestational hypertension and preeclampsia were more common in women with excessive GWG (37.9% versus 19.7%; p < 0.01). This finding persisted in multivariate analysis. The mean birth weight percentiles were higher in the excessive GWG group and these women were also less likely to have an infant with a birth weight <10th percentile (21.4% versus 35.9%, p < 0.01). Conclusions: Excessive GWG is associated with a higher risk for gestational hypertension and preeclampsia, but no other adverse perinatal outcomes. Infants born to mothers with excessive GWG are less likely to be small for gestational age than those born to women with adequate GWG.

Incidence of wound complications after cesarean delivery: is suture closure better?

Abstract Background: Wound complications (WC) following cesarean delivery (CD) result in significant morbidity. A randomized trial in 2013, which demonstrated lower WC rates with suture closure compared to staple closure, resulted in a practice change within our academic institution. Objective: To determine the impact of this practice change on WC rates and identify other modifiable risk factors for WC. Study design: This is a retrospective cohort study of all women undergoing CD at the University of California, San Diego between 1 March 2011 and 28 February 2012 (primarily staple) and 1 March 2013 and 28 February 2014 (primarily suture). WC rates were compared between the two time intervals using Chi-square and Student’s t-tests. Risk factors (OR, 95%CI) for WC were assessed using multiple logistic regression modeling. Results: Of 1580 women delivered by CD, rates of WC were higher with staple closure compared to sutures (10.1% versus 4.5%; OR 2.4, 1.4–4.1). Additionally, WC were more likely with vertical skin incisions (OR 3.6, 1.6–8.1), CD for failed labor (OR 2.9, 1.1–7.4) and diabetes (OR 2.1, 1.4–3.9). Conclusions: After adjusting for confounders, there were over twofold increased odds of WC with staple closure. Vertical incisions, failed labor and diabetes also contributed to WC. Suture closure appears to decrease the risks of WC post CD.

Rates of Gestational Weight Gain and Postpartum Weight Retention in Term Twin Pregnancies

INTRODUCTION: Our objective was to characterize gestational weight gain and postpartum weight retention in term twin pregnancies by body mass index (BMI) and trimester. METHODS: Retrospective cohort study including all term twin pregnancies at the University of California, San Diego Medical Center 2009–2013. Adequate gestational weight gain was determined by the 2009 Institute of Medicine guidelines for twin pregnancies. Students t test and the &khgr;2 test were used for analyses. RESULTS: Fifty-nine term twin pregnancies met inclusion criteria. Mean gestational weight gain for the cohort was 16.6±5.1 kg. According to Institute of Medicine guidelines, 15% had insufficient, 39% had sufficient, and 46% had excessive gestational weight gain. There were no differences in total gestational weight gain by chorionicity or BMI. The mean rates of gestational weight gain were 0.5±0.2 kg per week until 20 weeks of gestation, 0.7±0.3 kg per week at 20–28 weeks of gestation, and 0.7±0.4 kg per week from 28 weeks of gestation to term. Comparing rates of gestational weight gain between BMI groups, there were significant differences in rates of gestational weight gain before 20 weeks of gestation but no differences at 20–28 weeks of gestation and from 28 weeks of gestation to term. At the postpartum visit, 74% of normal, 93% of overweight, and 33% of obese women were within 5 kg of their first pregnancy weight (P=.02). CONCLUSIONS: The majority of twin pregnancies have sufficient gestational weight gain during their pregnancies and 46% exceed guidelines. Contrary to singletons, pregravid BMI does not adversely affect gestational weight gain. Beyond 20 weeks of gestation, gestational weight gain for women of different BMI groups occurs at similar rates. However, obesity is associated with a higher risk of postpartum weight retention in twin pregnancies.

The Effect of Gestational Weight Gain on Placental Inflammation in Obese Women [169].

INTRODUCTION: Previous studies have shown placental inflammation is more prevalent in obese women. Inflammation in the chorionic villi (“villitis”) of the placenta is associated with adverse pregnancy outcomes such as intrauterine growth restriction and preeclampsia. The objective of the study is to determine how gestational weight gain in obese women affects placental inflammation. METHODS: A retrospective review of placental pathology from obese women (body mass index [BMI, calculated as weight (kg)/[height (m)]2] 35 or higher) who delivered from 2011 to 2014 was conducted. The primary outcome was placental inflammation identified on pathologic examination. Inflammatory placental markers were compared in obese patients who had gained less than 50th% for gestational weight gain (low gestational weight gain) with those who gained greater than 50th% (high gestational weight gain). t tests and crosstabulations were used to compare inflammatory markers and gestational weight gain. RESULTS: Sixty-four obese women were included. The mean gestational weight gain in the low gestational weight gain group was 2.7±9.55 lbs compared with 35.1±12.80 lbs for the high gestational weight gain group. On placental pathology, villitis was common in all obese women (26.6%) but was not different between the gestational weight gain groups (P=.40). Fetal thrombosis, which can be associated with villitis, also did not occur more often in obese women with increased gestational weight gain (25.0% compared with 31.3%, P=.57). There were also no differences between placental infarct (29%, low gestational weight gain, compared with 9.4%, high gestational weight gain, P=.10) or placental weight (492 g, low gestational weight gain, compared with 536 g, high gestational weight gain, P=.85). CONCLUSION: Increased gestational weight gain does not appear to affect placental inflammatory markers in obese women in our cohort.

The association between second-trimester weight gain and preterm birth in twin pregnancies.

INTRODUCTION: Our objective was to determine whether inadequate gestational weight gain in the second trimester in twin pregnancies is associated with an increased risk of preterm birth before 32 weeks of gestation. METHODS: We performed a retrospective cohort study including all viable twin pregnancies delivered at UCSD Medical Center from 2009–2013. Adequate gestational weight gain rates were calculated by dividing the 2009 Institute of Medicine–recommended minimum total gestational weight gain by 37 weeks. Students t-test and the &khgr;2 test were used for bivariate analyses and logistic regression for multivariate analyses. RESULTS: One hundred sixty-nine twin pregnancies met inclusion criteria. Inadequate gestational weight gain at 20–28 weeks was associated with a significantly higher risk of preterm birth before 32 weeks (32% compared with 14%, P=.02) and spontaneous preterm birth before 32 weeks (26% compared with 9%, P=.01). Monochorionicity, cervical length less than 2.5 cm, and advanced maternal age were also significantly associated with preterm birth before 32 weeks. Multivariate analyses confirmed independent associations between inadequate gestational weight gain and cervical length less than 2.5 cm with preterm birth before 32 weeks (Table 1). Table 1 Associations With Preterm Birth Before 32 Weeks of Gestation in Multivariate Analysis CONCLUSIONS: Inadequate gestational weight gain at 20–28 weeks in twin pregnancies was the strongest predictor of preterm birth before 32 weeks. This may represent an optimal time for nutritional and counseling interventions to improve gestational weight gain and potentially decrease the rate of preterm birth.