Armin Witt

Expression of KLF5 is a prognostic factor for disease-free survival and overall survival in patients with breast cancer.

Purpose: Kruppel-like factor (KLF5) is a cell growth mediator in various epithelial cells. Higher KLF5 increases cell growth rate and leads to transformed phenotypes. Because tumor cell proliferation is tightly associated with tumor progression, and consequently, with survival of cancer patients, we wanted to examine the prognostic value of KLF5 gene expression for patients with breast cancer. Experimental Design: The gene expression levels of KLF5, ER, PR, HER2, and MKI67 were quantified in the tumor tissues of 90 patients with breast cancer and correlated with disease-free survival and overall survival of the patients. The correlations of gene expression between KLF5 and ER, PR, HER2, and MKI67 were analyzed. In addition, KLF5 expression was also compared with clinical data and age of patients. Results: Statistically significant correlations were found between gene expression of KLF5 and both disease-free survival (univariate analysis) and overall survival (univariate and multivariate analysis). Patients with higher KLF5 expression had shorter disease-free survival and overall survival time, whereas patients with lower KLF5 expression had better survival. Moreover, KLF5 was also found to be positively correlated with HER2 and MKI67, and negatively correlated with age of the patients at diagnosis. Conclusion: The gene expression of KLF5 is directly correlated with cell proliferation in vivo and is a prognostic factor for patients with breast cancer. Patients with higher KLF5 expression have shorter disease-free survival and overall survival than patients with lower KLF5 expression. In addition, KLF5 has higher expression in patients ages ≤50 years old than in patients >50 years old.

The bacterial load of Ureaplasma parvum in amniotic fluid is correlated with an increased intrauterine inflammatory response

Ureaplasma spp. are the most frequently isolated microorganisms inside the amniotic cavity and have been associated with spontaneous abortion, chorioamnionitis, premature rupture of the membranes (PROM), and preterm labor (PL). We analyzed 118 samples from amniotic fluid of preterm infants before 34 weeks of gestation by quantitative polymerase chain reaction (qPCR). Bacterial load, Ureaplasma biovar discrimination (Ureaplasma urealyticum and Ureaplasma parvum), and the level of inflammation were correlated with short-term clinical outcome. U. parvum was the predominant biovar, and increased bacterial load was significantly linked to histologic chorioamnionitis, PROM + PL, early-onset sepsis, and bronchopulmonary dysplasia. Furthermore, there was a positive correlation between the amount of U. parvum and the magnitude of inflammatory response inside the amniotic cavity observed by elevated interleukin 8 levels. We postulate that the bacterial load of Ureaplasma spp. measured by qPCR should be determined in studies investigating the potential clinical impact of intrauterine Ureaplasma spp. on the outcome of preterm infants.

IL-8 concentrations in maternal serum, amniotic fluid and cord blood in relation to different pathogens within the amniotic cavity.

Abstract Objective: The association between elevated interleukin (IL)-8 concentrations in amniotic fluid and preterm delivery is well described. Little consideration has been given to the impact of different groups of microorganisms within the amniotic cavity on IL-8 concentration. Methods: We collected amniotic fluid, placental tissue and amniotic membranes during preterm cesarean sections for bacterial culture. In addition, we determined IL-8 concentrations in maternal serum, amniotic fluid and cord blood and correlated them with the various intra-amniotic pathogens isolated by bacterial culture. Results: IL-8 concentrations were determined in amniotic fluid in 107 cases, in cord blood in 185 cases and in maternal blood in 158 cases. Women with intra-amniotic Ureaplasma urealyticum infection had significantly higher amniotic fluid concentrations of IL-8 than those without (P<0.001). In cord blood, we found significantly elevated IL-8 concentrations due to intra-amniotic infection with U. urealyticum (P=0.045) and other pathogens (P=0.04). In maternal sera, we found no significant elevation of maternal IL-8 in any of the groups. Conclusion: Intrauterine infection with U. urealyticum seems to play a profound role in the cascade of inflammation and increases IL-8 concentrations in amniotic fluid and cord blood.

In utero exposure to Ureaplasma spp. is associated with increased rate of bronchopulmonary dysplasia and intraventricular hemorrhage in preterm infants.

Abstract Aims: We determined the association between short-term neonatal morbidities, such as bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH), and Ureaplasma spp. in amniotic fluid, placental and amniotic mem-brane of preterm infants. Methods: This study enrolled 257 patients who were born by cesarean section at <34 weeks’ gestation. Patients were divided into two groups according to detection of Ureaplasma spp. by culture-based and/or polymerase chain reaction (PCR) techniques. Results: Significant differences were observed between both groups for all IVH (P=0.032) and IVH grades III or IV (P=0.013), as wells as for BPD [odds ratio (OR) 5.46, 95% confidence interval (CI) 2.02–14.77], oxygen requirement at 28 days postnatal age (OR 1.93, 95% CI 1.00–3.70), and for death between 28 days and 36 postmenstrual weeks or BPD (OR 4.20, 95% CI 1.77–9.96). Ureaplasma spp. was a significant predictor (P<0.001) of BPD after correcting for birth weight (P=0.003) and positive pressure ventilation (P=0.001). Conclusions: In our study population Ureaplasma spp. was associated with BPD and IVH in preterm infants even after adjustment for multiple risk factors.

DNA Hybridization Test: Rapid Diagnostic Tool for Excluding Bacterial Vaginosis in Pregnant Women with Symptoms Suggestive of Infection

ABSTRACT This prospective comparative study evaluated a DNA hybridization test (Affirm VPIII) as an alternative to Gram stain for the diagnosis of bacterial vaginosis. We examined vaginal smears from 1,725 pregnant women between the 12th and 36th weeks of gestation with clinical signs of vaginal infection. The DNA hybridization test compared well with Gram stain and can be used as a rapid diagnostic tool to exclude bacterial vaginosis.

Microbial invasion of the amniotic cavity at birth is associated with adverse short-term outcome of preterm infants.

Abstract Aims: To determine the frequency and clinical significance of microbial invasion of the amniotic cavity at the time of delivery in preterm infants. Methods: Prospective cohort study during June 2001 and January 2002. Preterm infants < 33+6 weeks of gestation who had amniotic fluid and placental tissue sampled for culture during cesarean section were included. Results: Of a total of 80 neonates, 42 had negative culture results, 22 had growth of Ureaplasma urealyticum, and 16 had growth of other pathogens. Isolation of Ureaplasma urealyticum was associated with a decreased risk of developing hyaline membrane disease after birth but a more than 20 times increased risk of developing chronic lung disease. Patients with growth of other pathogens had a significantly higher mortality than patients with negative culture results. Conclusions: Isolation of microorganisms from the amniotic cavity at birth is associated with an adverse outcome of the preterm infant. In the light of extremely small numbers of positive blood cultures in preterm infants after birth, we consider it reasonable to recommend routine culturing of amniotic cavity tissues/fluid obtained during cesarean section in order to increase the identification rate of pathogens potentially involved in the pathogenesis of perinatal infections.

Prediction of spontaneous preterm delivery in twin pregnancies by cervical length at mid-gestation.

The objective of our study was to evaluate the correlation of the cervical length at 20-25 weeks of gestation with the incidence of spontaneous preterm delivery in twins in a country with a high incidence of preterm delivery compared to other European countries. Cervical length was measured in 262 consecutive patients. Previous preterm delivery before 34 weeks of gestation, chorionicity, maternal age, body-mass-index, smoking habit and parity were recorded as risk factors for preterm delivery. Women who were symptomatic at 20-25 weeks and who delivered because of other reasons than spontaneous labour and preterm rupture of membranes or at term were excluded. The primary outcome was incidence of preterm birth before 34 weeks. Two hundred and twenty-three patients were analyzed. Thirty-two (14%) delivered before 34 weeks. There was a significant correlation between cervical length of less than 25 mm and spontaneous delivery before 34 weeks (50% vs. 13%, p = .007). In addition, logistic regression analysis found cervical length to be the only significant predictor of spontaneous delivery before 34 weeks (OR 1.084; 95% CI 1.015; 1.159; p = .017). We conclude that the risk of severe preterm delivery in twins is high. Cervical length at mid-gestation was the only predictor of delivery before 34 weeks.

Amniotic cavity cultures, blood cultures, and surface swabs in preterm infants--useful tools for the management of early-onset sepsis?

Abstract Aims: To evaluate the potential benefit of amniotic fluid and amniotic/placental membrane cultures for the management of early-onset sepsis in preterm infants. Methods: The results of amniotic cavity cultures obtained during cesarean section and of peripheral blood cultures and surface swabs obtained from the preterm infant at the time of admission were analyzed with respect to the diagnosis of clinical sepsis in 221 preterm infants <34 weeks of gestation. Results: 136 (61.5%) patients had negative amniotic cavity culture results or growth of contaminants, 56 (25.3%) had growth of Ureaplasma urealyticum, and 29 (13.1%) of other pathogens. The corresponding numbers for surface swabs were 82.8%, 11.6%, and 5.6%. A positive blood culture was found in only two neonates. Fifty-four patients (24.4%) had clinical early-onset sepsis. Patients with amniotic cavity culture results that were positive for other pathogens were significantly more likely to experience clinical sepsis than patients with negative culture results (51.7% vs 15.1%, OR 6.1, p < 0.0001). Regarding surface swabs, this correlation did not reach statistical significance. Conclusion: The strong association between positive amniotic cavity culture results and clinical early-onset sepsis supports the existence of a causal relation and provides evidence for the potential value of amniotic and/or placental membrane sampling in the management of early-onset sepsis in preterm infants. Surface swabs add no additional information and hence should not be performed routinely.

First Trimester Vaginal Ureaplasma Biovar Colonization and Preterm Birth: Results of a Prospective Multicenter Study

Background: While there is a proven association of upper genital tract Ureaplasma infection during pregnancy with adverse pregnancy outcome, the effect of vaginal Ureaplasma colonization on preterm delivery has been controversially debated. Objectives: We hypothesized that women with isolation of vaginal U. parvum but not U. urealyticum are at increased risk for spontaneous preterm birth (SPB) compared to women with negative results. Methods: A vaginal swab taken between 12 and 14 weeks of gestation was analyzed for the presence of Ureaplasma biovars by PCR in 4,330 pregnant women. Results: Of the study cohort, 37% were positive for U. parvum, 5.9% for U. urealyticum, and 3.1% for both. The rates of SPB were 10.4% (OR 1.7, 95% CI 1.3, 2.2, p < 0.001) and 8.9% (OR 1.4, 95% CI 0.9, 2.3, p = 0.193) in the groups with isolation of U. parvum and U. urealyticum, respectively, compared to 6.4% in the group with negative PCR results. Multiple logistic regression and interaction analyses showed that vaginal colonization with U. parvum but not U. urealyticum was a statistically significant risk factor for SPB (adjusted OR 1.6, 95% CI 1.2, 2.1, p < 0.001), independent of other risk factors such as bacterial vaginosis and history of SPB. Conclusion: Our study demonstrates a statistically significant and independent association between first-trimester vaginal colonization with U. parvum and subsequent SPB.

OC141: Prediction of spontaneous preterm delivery in twin pregnancies by cervical length at mid‐gestation

measurement of the cervix better reflects the engineering principle that greater tissue volume equals greater resistance to dilatation than cervical length. The aim of the study was to determine if cervical volume is a more reliable predictor of preterm delivery than cervical length. Methods: Patients were recruited between 19 and 34 weeks’ gestation if they were shown to have uterine contractions and/or cervical change as determined by pelvic examination or abnormally short (< 28 mm) cervical length. The cervical length and cervical volume were obtained using standard transvaginal 2D and 3D study. Delivery information was subsequently obtained. Data pertaining to cervical length and cervical volume were analyzed postpartum. Results: To date, cervical length, cervical volume and outcome parameters are available for 37 patients. Twenty-two of these patients delivered preterm (< 37 weeks GA). The mean gestational age at delivery (preterm) was 31.4 + 4.1 weeks. Mean maternal age was 22.28 + 6.67 years. Cervical volume was more predictive of risk for preterm delivery than cervical length (sensitivity 95.5%, specificity 73.4%, positive predictive value 84%, negative predictive value 91.7%). Based on the limited data available to date, ROC analysis demonstrated that cervical volume is a better predictor of preterm delivery risk. The area under the curve was 854 for cervical volume vs. 721 for cervical length. Conclusions: Our data strongly suggest that cervical volume is a better predictor of preterm delivery than cervical length. We continue to actively recruit patients to reach the number of patients needed statistically to conclude the study.