Dagmar Bancher-Todesca

CD44 is an independent prognostic factor in early-stage cervical cancer.

The expression of specific cell‐adhesion molecule CD44 isoforms (splice variants) is associated with metastatic spread and poor prognosis in human malignancies. The aim of this study was to evaluate whether CD44 isoform expression is a prognostic factor in early‐stage cervical cancer. We used 4 different variant exon sequence‐specific murine monoclonal antibodies to the CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7‐8 to study the prognostic value of CD44 splice variants in 200 cases of International Federation of Gynecology and Obstetrics (FIGO) stage‐IB cervical cancer by immunohistochemistry. In the univariate analysis, the expression of CD44v3 (log‐rank test, p = 0.03) and CD44v6 (log‐rank test, p = 0.03) was correlated with poor overall survival. In the subgroup of patients without metastatic disease in the pelvic lymph nodes, expression of CD44v6 was correlated with poor disease‐free and overall survival (log‐rank test, p = 0.04 and p = 0.01, respectively). Multivariate analysis, correcting for the confounding variables pelvic lymph‐node involvement, depth of invasion and histologic grading, revealed CD44v6 to be an independent prognostic factor for overall survival of patients with early‐stage cervical cancer. The results of this study indicate that CD44v6 is an additional prognostic marker in surgically treated cervical cancer. The assessment of CD44 isoform expression could be of clinical value in deciding upon adjuvant therapy, resulting in a more individualized management of therapy. Int. J. Cancer 74:185–188, 1997.

The Impact of Risk Factors and More Stringent Diagnostic Criteria of Gestational Diabetes on Outcomes in Central European Women

OBJECTIVES In the face of the ongoing discussion on the criteria for the diagnosis of gestational diabetes (GDM), we aimed to examine whether the criteria of the Fourth International Workshop Conference of GDM (WC) select women and children at risk better than the World Health Organization (WHO) criteria. DESIGN AND SETTING This was a prospective longitudinal open study in five tertiary care centers in Austria. PATIENTS AND OUTCOME MEASURES The impact of risk factors, different thresholds (WC vs. WHO), and numbers of abnormal glucose values (WC) during the 2-h, 75-g oral glucose tolerance test on fetal/neonatal complications and maternal postpartum glucose tolerance was studied in 1466 pregnant women. Women were treated if at least one value according to the WC (GDM-WC1) was met or exceeded. RESULTS Forty-six percent of all women had GDM-WC1, whereas 29% had GDM-WHO, and 21% of all women had two or three abnormal values according to WC criteria (GDM-WC2). Eighty-five percent of the GDM-WHO were also identified by GDM-WC1. Previous GDM [odds ratio (OR) 2.9], glucosuria (OR 2.4), preconceptual overweight/obesity (OR 2.3), age 30 yr or older (OR 1.9), and large-for-gestational age (LGA) fetus (OR 1.8) were the best independent predictors of the occurrence of GDM. Previous GDM (OR 4.4) and overweight/obesity (OR 4.0) also independently predicted diabetes postpartum. GDM-WC1 had a higher rate of obstetrical complications (LGA neonates, neonatal hypoglycemia, cesarean sections; P < 0.001) and impaired postpartum glucose tolerance (P < 0.0001) than GDM-WHO. CONCLUSION These results suggest the use of more stringent WC criteria for the diagnosis of GDM with the initiation of therapy in case of one fasting or stimulated abnormal glucose value because these criteria detected more LGA neonates with hypoglycemia and mothers with impaired postpartum glucose metabolism than the WHO criteria.

Calpain-10 haplotype combination and association with gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a frequent complication of pregnancy. Epidemiologic and pathophysiologic data suggest a close link of this disease to non-insulin-dependent diabetes mellitus. Within the calpain-10 gene various single-nucleotide polymorphisms have been identified that increased the risk for non-insulin-dependent diabetes mellitus. Therefore, we examined single-nucleotide exchanges of this gene in women with GDM. METHODS: A total of 875 unselected women were prospectively screened for GDM. Eighty women of this population, 40 patients with an abnormal oral glucose tolerance test and 40 normal controls, were randomly selected. DNA samples isolated from sera of the control and study groups were analyzed with respect to single-nucleotide polymorphisms of the calpain-10 gene at positions 43, 19, and 63 using polymerase chain reaction amplification and restriction analysis. RESULTS: Women with GDM were more likely to be homozygous for the allele 1 of single-nucleotide polymorphism 63 (P = .02 by χ2 test). With respect to single-nucleotide polymorphisms 19 and 43, no significant differences in allele distribution were detected between controls and women with GDM. When comparing the different haplotypes for calpain-10 (single-nucleotide polymorphisms 43, 19, and 63), all women with the haplotype combination 121/221 (n = 8) had gestational diabetes (P = .005 by Fisher exact test). CONCLUSION: Our results indicate that the haplotype 121/221 of the calpain-10 gene may be associated with disturbances of glucose metabolism during pregnancy. LEVEL OF EVIDENCE: II-1

Short-term effects of topical testosterone in vulvar lichen sclerosus

Objective To evaluate the systemic and therapeutic effect of topical testosterone treatment in vulvar lichen sclerosus. Methods This prospective clinical, single-arm study included ten postmenopausal women with vulvar lichen sclerosus. Testosterone propionate (0.04 g daily) was administered topically for 4 weeks. Serum androgens (testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate) were determined before and after 4 weeks of treatment, and vulvodynia was evaluated by a horizontal visual analogue scale. Results Serum levels of total testosterone increased in all patients (P Conclusion Topical testosterone is effective in normoandrogenic women with lichen sclerosus. Androgen status should be evaluated before treatment, and dosage should be individualized to avoid virilization and metabolic side effects. Because there is a marked systemic effect, clinical controls and a follow-up with evaluation of serum testosterone levels are recommended. Other steroids should be included in therapeutic decisions.

Risk Factor Profile and Pregnancy Outcome in Women with Type 1 and Type 2 Diabetes Mellitus

OBJECTIVE To assess differences in congenital anomalies, infant mortality, and obstetrical complications as well as risk factors associated with an adverse pregnancy outcome in women with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). METHODS This observational study was performed at a university clinic and included a total of 200 singleton pregnancies between January 1995 and December 2006. Outcome measures comprise the prevalence of major congenital malformations, fetal losses, stillbirths, and neonatal deaths as well as the combined end point, adverse pregnancy outcome, and obstetrical complications. RESULTS Despite changes in prevailing risk factors, the rate of congenital anomalies and embryonic as well as perinatal death was comparable in type 1 diabetic women over time as well as between women with T1DM and T2DM. Outcome measures and risk factor profile were similar in women with preconception and newly diagnosed T2DM. Glycemic control and increased body mass index (BMI) during the first trimester were the strongest predictors of an adverse pregnancy outcome. Hemoglobin A1c (HbA1c) was higher in T1DM than in T2DM but similar in women with T1DM over time. BMI was highest in women with T2DM, followed by T1DM women of the most recent time period. CONCLUSIONS In addition to HbA1c, other risk factors, especially high BMI, strongly influence pregnancy outcome. The higher prevalence of these risk factors in T2DM might compensate for the better glycemic control, resulting in a pregnancy outcome comparable to that of T1DM. Pregnancy outcome in T1DM remained unchanged over time, possibly because of the missing amelioration of HbA1c levels and the increasing BMI.

IADPSG and WHO 2013 Gestational Diabetes Mellitus Criteria Identify Obese Women With Marked Insulin Resistance in Early Pregnancy

Implementation of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and the World Health Organization 2013 (WHO 2013) recommendations leads to an increased prevalence of gestational diabetes mellitus (GDM) due to more stringent criteria and early screening of women at high risk for diabetes in pregnancy (DIP) (1,2). IADPSG members now recommend that their GDM criteria should not be used in early pregnancy but have not provided alternative criteria (3). We have compared the characteristics of overweight/obese women early in pregnancy, with and without GDM using the new criteria, to assess whether those testing positive are metabolically distinct. Pregnant women with a BMI ≥29.0 kg/m2 underwent a 75-g oral glucose tolerance test in early pregnancy as part of enrollment into the DALI (Vitamin D And Lifestyle Intervention for GDM prevention) pilot and lifestyle Pan-European multicenter trials (4). GDM and DIP were diagnosed using WHO 2013 criteria. A high rate of GDM (237/1,035 or 22.9%: DIP 0.5%; total hyperglycemia in early pregnancy 23.4%) was found at a …

Iodine deficiency in pregnant women in Austria

Background/Objectives:In Austria, iodine deficiency has been considered to be eliminated owing to table salt fortification with iodine, but whether this also applies to pregnant women is unclear. Even mild iodine deficiency during gestation may lead to neurocognitive sequelae in the offspring.Subjects/Methods:This is a cross-sectional investigation of urinary iodine excretion in 246 pregnant women (first trimester n=2, second trimester n=53, third trimester n=191, gestational diabetes mellitus n=115, no gestational diabetes mellitus n=131). The iodine content of morning spot urine samples was determined using inductively coupled plasma mass spectrometry.Results:Pregnant women in the Vienna area had a median urinary iodine concentration (UIC) of 87 μg/l. Only 13.8% of the cohort were in the recommended range of 150–249 μg/l, whereas 21.5% had a UIC of 0–49 μg/l, 40.2% had a UIC of 50–99 μg/l and 19.5% had a UIC of 100–149 μg/l. In all, 4.9% had a UIC over 250 μg/l. A total of 137 women of foreign origin had a significantly higher iodine excretion compared with Austrian-born women. Maternal or gestational age had no influence on UIC. Although 79 women on iodine supplementation had a significantly higher iodine concentration compared with women without iodine supplementation (97.3 vs 80.1 μg/l, P=0,006), their UIC was below the recommended range, indicating that doses of 100–150 μg per day are not sufficient to normalize iodine excretion. Sodium and iodine concentrations in the urine were tightly correlated (R=0.539, n=61), suggesting that low intake of iodized salt might contribute to insufficient iodine supply.Conclusions:This study shows that pregnant women in the Vienna area have a potentially clinically significant iodine deficiency and that currently recommended doses of iodine supplementation may not be sufficient.

Placental expression and serum concentrations of cytokeratin 19 in preeclampsia.

Objective To evaluate cytokeratin 19 as a serum marker of preeclampsia. Methods Serum cytokeratin 19 levels were measured in 46 women with preeclampsia and 46 controls matched for gestational age and parity, using an immunoradiometric assay. Cytokeratin 19 was evaluated immunohistochemically in placental specimens from 28 healthy pregnant women and 24 women with preeclampsia. Results Cytokeratin 19 was identified in the syncytiotrophoblast in 13 (46.4%) of 28 and 23 (95.8%) of 24 placental specimens from controls and women with preeclampsia, respectively (P = .03). Median serum levels of cytokeratin 19 in controls and women with preeclampsia were 1.7 (range 0.3–4.7) μg/mL and 2.7 (range 0.8–8.2) μg/mL, respectively (P < .001). Cytokeratin 19 significantly influenced the odds of presenting with preeclampsia (P < .001) and the odds of developing severe disease (P < .001). Serum cytokeratin 19 correlated inversely with fetal birth weight (Kendall τ-b correlation coefficient = −0.2, P = .007). Compared with healthy pregnant women, women with severe preeclampsia had significantly higher and more rapidly increasing cytokeratin 19 serum levels throughout the third trimester (P < .001). Conclusion Placental stimulation of cytokeratin 19, and release of it into maternal circulation, seem to be a feature of preeclampsia. Correlations with clinical characteristics suggest that cytokeratin 19 is a marker of disease severity.

Changes in Serum Lipid Levels During Pregnancy in Type 1 and Type 2 Diabetic Subjects

OBJECTIVE Alterations in maternal lipid metabolism could affect fetal programming and the susceptibility for atherosclerosis in the offspring; therefore, we studied differences in lipid profiles of pregnant women with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 173 diabetic pregnancies were studied prior to conception (V0), at each trimester (V1–V3), and after delivery and were compared with 137 healthy women at V3. RESULTS During gestation, the increase in serum lipid concentrations was less pronounced in type 2 diabetic subjects. At V3, the lipid levels of type 1 diabetic women with normal glucose tolerance were similar but significantly higher then those of type 2 diabetic women. Elevated triglycerides and low HDL cholesterol at V3 were significant predictors for large-for-gestational-age (LGA) newborns. CONCLUSIONS Our data suggest smaller changes in serum lipid concentrations during pregnancy in type 2 diabetic mothers. Additionally, we found a positive association between maternal triglycerides and LGA infants independently of chronic glycemic control.

Pathophysiological Characteristics and Effects of Obesity in Women With Early and Late Manifestation of Gestational Diabetes Diagnosed by the International Association of Diabetes and Pregnancy Study Groups Criteria

CONTEXT Appropriate risk stratification is essential in gestational diabetes (GDM) diagnosis to optimize therapeutic strategies during pregnancy. However, there are sparse data related to the newly recommended International Association of Diabetes and Pregnancy Study Groups criteria and their use in early pregnancy. OBJECTIVE This study sought to evaluate clinical and pathophysiological characteristics less up to gestational week (GW) 21 in women with early and late GDM onset. DESIGN AND SETTING This was a prospective study conducted at the Medical University of Vienna. PATIENTS AND INTERVENTIONS Pregnant women (n = 211) underwent an oral glucose tolerance test at 16 GW (interquartile range, 14-18 wk) with multiple measurements of glucose, insulin, and C-peptide for evaluation of insulin sensitivity and ß-cell function in addition to detailed obstetrical risk assessment. Clinical followups were performed until end of pregnancy. MAIN OUTCOME MEASURE We performed a metabolic characterization of early-onset GDM. RESULTS Of 81 women, 49 (23%) showed early (GDMEarly ≤ 21 GW) and 32 (15%) later manifestation (GDMLate ≥ 24 GW) whereas 130 (62%) remained normal-glucose-tolerant (NGT). In contrast with GDMLate, GDMEarly were affected by decreased insulin sensitivity (GDMEarly vs NGT, P < .001; GDMEarlyvs GDMLate, P < .001; GDMLate vs NGT, P = .410). However, both early and late manifested subjects showed impairments in ß-cell function. GDMEarly showed highest levels of preconceptional and actual body mass index (BMI), which was related to fasting glucose (r = 0.42, P < .001) and particularly insulin sensitivity (r = -0.51, P < .001). Differences in glucose disposal between the subgroups remained constant in multivariable analysis including the strongest risk factors for GDM, ie, age, history of GDM, and BMI in our population. CONCLUSIONS Early manifestation of GDM is affected by insulin resistance that is partly explained by higher degree in obesity. However, ß-cell dysfunction was also detectable in GDMLate, indicating defective compensatory mechanisms emerging already in early pregnancy.