Change in prevalence of gestational diabetes and obstetric complications when applying IADPSG screening criteria in a Belgian French speaking University Hospital. A retrospective cohort study.

BACKGROUND: In April 2012 our institution chose to switch from a two- step criteria for Gestational Diabetes Mellitus (GDM) screening, to the International Association of Diabetes in Pregnancy Study Group (IADSPG) criteria. This shift led to an increased prevalence of GDM in our pregnant population. We designed a study in order to estimate the magnitude of the increase in GDM prevalence before and after the switch in screening strategy. As a secondary objective we wanted to evaluate if there was a significant difference between the two periods in the percentage of maternal and neonatal complications such as gestational hypertensive disorders (GHD), primary cesarean section (pCS), preterm birth, large for gestational age (LGA) newborns, macrosomia, shoulder dystocia, 5' Apgar score less than to 7 at birth, neonatal intensive care unit (NICU) transfer and neonatal hypoglycemia. METHODS: We selected retrospectively 3496 patients who delivered between January 2009 and December 2011 who were screened with the two-step criteria (group A), and compared them to 2555 patients who delivered between January 2013 and December 2014 and who were screened with IADPSG criteria (Group B). We checked patients' electronic files to establish GDM status, baseline characteristics (age, body mass index, nationality, parity) and the presence of maternal and neonatal complications. RESULTS: GDM prevalence increased significantly from group A (3.4%; 95%CI 2.8-4.06%) to group B (16.28%; 95%CI 14.8 -17.7%). In group B there were significantly more non-Belgian and primiparous patients. There was no statistically significant difference in maternal and neonatal complications between the two groups, even after adjustment for nationality and parity. There was a non-significant reduction of the proportion of macrosomic and of LGA babies. CONCLUSIONS: In our population the introduction of IADPSG screening criteria has increased the prevalence of GDM without having a statistically significant impact on pregnancy outcomes.

Local applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions.

PROBLEM: Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished capacity to capture viral antigens and to induce a protective immune response. METHOD OF STUDY: To test whether a cervical application of GM-CSF could restore an immune response against HPV in women with cervical low-grade squamous intraepithelial lesions (LSIL), we performed two clinical trials with 11 healthy women and 15 patients with LSIL. RESULTS: GM-CSF applications were well tolerated in all enrolled women, and no difference in toxicity between the treated and placebo groups was observed during the follow-up (until 30 months). Interestingly, in the GM-CSF treated group, a significant increase of APC and cytotoxic T-lymphocyte infiltration was observed in the cervical biopsies with no change in regulatory T cell numbers. All the HPV16(+) patients exhibited an immune response against HPV16 after GM-CSF applications, as shown by NK and/or T cells producing IFN-gamma whereas no cellular immune response was observed before the treatment. Moreover, the anti-virus-like particles antibody titers also increased after the treatment. CONCLUSION: These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions.

Effects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18-35 years old.

BACKGROUND: Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. STUDY DESIGN: A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone have been compared to a matched control group of 30 noncontraception users (NCU). Blood levels of antioxidants, trace elements and markers of lipid peroxidation were assessed by biochemical methods. A microarray analysis of whole blood mRNA levels of 200 genes involved in OS-dependant pathway was also performed. RESULTS: Levels of zinc, vitamin E and antibodies to oxidized low-density lipoproteins (LDLs) were not significantly different between the two groups. On the other hand, significant increases in the mean levels of lipid peroxides (+176%, p<.001), oxidized LDLs (+145%, p<.002), copper (+103%, p<.001), Cu/Zn ratio (+100%, p<.001) and a significant decrease in the mean level of beta-carotene (-41%, p<.01) were observed in the OCU compared to NCU. There was a highly significant positive correlation between the lipid peroxide levels and the copper-to-zinc ratio. From the 200 genes tested by microarray, one coding for HSP70 was significantly up-regulated (log(2) fold change=+ 0.45, p<.02) and one coding for inducible nitric oxide synthase significantly down-regulated (log(2) fold change=-0.24, p<.05) in the OCU compared to the NCU. CONCLUSIONS: The recently introduced combination of ethinylestradiol and drospirenone induced the heightening of lipid peroxidation correlated with high levels of copper, a situation that could be associated with increased cardiovascular risk.

Phase I/II trial of immunogenicity of a human papillomavirus (HPV) type 16 E7 protein-based vaccine in women with oncogenic HPV-positive cervical intraepithelial neoplasia.

PURPOSE: Infection with oncogenic human papillomavirus (HPV) and HPV-16 in particular is a leading cause of anogenital neoplasia. High-grade intraepithelial lesions require treatment because of their potential to progress to invasive cancer. Numerous preclinical studies have demonstrated the therapeutic potential of E7-directed vaccination strategies in mice tumour models. In the present study, we tested the immunogenicity of a fusion protein (PD-E7) comprising a mutated HPV-16 E7 linked to the first 108 amino acids of Haemophilus influenzae protein D, formulated in the GlaxoSmithKline Biologicals adjuvant AS02B, in patients bearing oncogenic HPV-positive cervical intraepithelial neoplasia (CIN). METHODS: Seven patients, five with a CIN3 and two with a CIN1, received three intramuscular injections of adjuvanted PD-E7 at 2-week intervals. Three additional CIN1 patients received a placebo. CIN3 patients underwent conization 8 weeks postvaccination. Cytokine flow cytometry and ELISA were used to monitor antigen-specific cellular and antibody responses from blood taken before and after vaccine or placebo injection. RESULTS: Some patients had preexisting systemic IFN-gamma CD4+ (1/10) and CD8+ (5/10) responses to PD-E7. Vaccination, not placebo injection, elicited systemic specific immune responses in the majority of the patients. Five vaccinated patients (71%) showed significantly increased IFN-gamma CD8+ cell responses upon PD-E7 stimulation. Two responding patients generated long-term T-cell immunity toward the vaccine antigen and E7 as well as a weak H. influenzae protein D (PD)-directed CD4+ response. All the vaccinated patients, but not the placebo, made significant E7- and PD-specific IgG. CONCLUSIONS: The encouraging results obtained from this study performed on a limited number of subjects justify further analysis of the efficacy of the PD-E7/AS02B vaccine in CIN patients.