Multiple foreign body granulomas after mastectomy with intraoperative application of tissue adhesive vs. surgical drainage - sonographic finding.

PURPOSE: The use of tissue adhesive instead of a drain following mastectomy was a point of interest for many breast surgeons. Postoperative formation of multiple unusual sonographic lesions was observed in patients that underwent mastectomy with TissuGlu. The aim of this study was to describe the sonographic features of these lesions and, when possible, to examine them histologically. MATERIALS AND METHODS: This study includes 98 patients, 49 underwent mastectomy with the application of TissuGlu and 49 with drain insertion. Unusual postoperative sonographic findings were thoroughly described. A histological examination was carried out according to the guideline recommendations. RESULTS: Unusual sonographic findings were detected in 87.8% of patients in the TissuGlu group and in only 4% of the patients in the drain group. These lesions were detectable between 6 and 59 months postoperatively. 47 breasts of the TissuGlu group were classified as category 3, while only 2 breasts as category 4. Lesions were on average 7.5 mm in diameter, echogenic or isoechoic with posterior shadowing, an irregular and ill circumscribed marginal contour, and a horizontal axis. All histologically examined lesions (n=29) were benign. Granulomatous tissue was histologically proven in 63% of those lesions (n=17), while residual adhesive material could be detected in 18.5% of lesions (n=5). CONCLUSION: The use of TissuGlu adhesive after mastectomy may cause the formation of unusual palpable granulomas, with or without residual adhesive materials. Sonographic description of lesions will help physicians to differentiate between granulomas and local relapse.

Real-Time Walk Error Compensation Method Using Echo Signal Magnitude Measurement in ToF Laser Scanners.

The rapid advancement of mobile laser scanner technology used for terrain mapping, among other things, imposes increasing requirements for scanning frequency and distance measurement accuracy. To meet these requirements, rangefinder modules are expected to operate with high echo signal dynamics and to allow accurate distance measurement even based on single-laser-pulse echo detection. Such performance can be potentially achieved using pulsed time-of-flight (ToF) laser rangefinders (LRF). In conventional ToF modules, however, the STOP signal (for time counter interruption) is generated using a straightforward fixed-threshold comparator method. Unfortunately, it corresponds to the so-called walk error, i.e., the dependence of the measured time of flight on the magnitude of the echo signal. In most ranging applications, however, the LRF detection channel can be exposed to an extremely large span of received echo power levels, which depend on the distance measured, type of target surface, atmospheric transmission, etc. Thus, the walk error is an inseparable element of the conventional ToF technique and creates a fundamental limit for its precision. This article presents a novel method of walk error compensation in real time. By using our authorial electronic circuit for measuring the magnitude of the echo signal, it is possible to effectively compensate for the walk error even when the echo signal brings the detection channel amplifiers into saturation. In addition, the paper presents a laboratory method for calibrating the walk error compensation curve.

Maternal socioeconomic and lifestyle factors and life dissatisfaction associated with a small for gestational age infant. The Survey of Neonates in Pomerania (SNiP).

PURPOSE: The aim is to investigate the associations of the mother's socioeconomic and lifestyle factors and life satisfaction with the delivery of a small for gestational age (SGA) infant. METHODS: Data from 4598 participants of the population-based birth cohort study Survey of Neonates in Pomerania (SniP) including comprehensive information on pregnancies, mothers, and their offspring in Western Pomerania, Germany were used in this study. The associations were analyzed using linear and logistic regression models. RESULTS: After logistic regression analysis adjusted for height of the mother, women who delivered SGA infants, had lower education (p < 0.01) and smoked more frequently during pregnancy (p < 0.01) compared with mothers of adequate for gestational age (AGA) neonates. A mother with less than 10 years of education and one who continued smoking during pregnancy had an odds ratio (OR) of 2.23 [95% confidence interval (CI) = 1.44 to 3.46] and 2.68 (95% CI = 2.06-3.49) of having an SGA infant, respectively. There was no association between the employment of the mother (p = 0.28), the monthly income (p = 0.09), the family status (p = 0.80), the number of friendships outside the household that the mother would not wish to relinquish (p = 0.47), the number of people that she could rely on in case of an emergency (p = 0.75), or alcohol consumption prior to (p = 0.14) or during the pregnancy (p = 0.99) with SGA. Finally, women who delivered SGA infants were more frequently dissatisfied with their employment (p = 0.03) and financial status (p < 0.01). CONCLUSIONS: Women who delivered SGA infants had more associated socioeconomic and lifestyle risk factors and were more frequently dissatisfied with their life conditions than mothers of AGA neonates.

Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions.

Early pregnancy is marked by placentation and embryogenesis, which take place under physiological low oxygen concentrations. This oxygen condition is crucial for many aspects of placentation, trophoblast function, vascularization and immune function. Recently, a new family of innate lymphoid cells has been found to be expressed at the fetomaternal interface. Among these, type 3 innate lymphoid cells (ILC3) are important antigen presenting cells in the context of MHC-II. The expression of MHC-II on ILC3s during pregnancy is reduced. We tested the hypothesis that low oxygen concentrations reduce the potential of ILC3s to present antigens promoting fetal tolerance.Using an in vitro approach, NCR+ ILC3s generated from cord blood stem cell precursors were incubated under different O2 concentrations in the presence or absence of the pregnancy-related hormones hCG and TGF-ß1. The expression of MHC-II, accessory molecules and an activation marker were assessed by flow cytometry. We observed that 1% O2 reduced the expression of the MHC-II molecule HLA-DR as compared to 21% O2 and modulated the relative effects of hCG and TGF-ß1.Our data indicate that low oxygen concentrations reduce the antigen presentation potential of NCR+ ILC3s and suggest that it may promote fetal tolerance during the first trimester of pregnancy.

B cells acquire a unique and differential transcriptomic profile during pregnancy.

Pregnancy alters B cell development and function. B cell activation is initiated by antigens binding to the BCR leading to B cell survival, proliferation, antigen presentation and antibody production. We performed a genome-wide transcriptome profiling of splenic B cells from pregnant (P) and non-pregnant (NP) mice and identified 1136 genes exhibiting differential expression in B cells from P mice (625 up- and 511 down-regulated) compared to NP animals. In silico analysis showed that B cell activation through BCR seems to be lowered during pregnancy. RT-qPCR analysis confirmed these data. Additionally, B cells from pregnant women stimulated in vitro through BCR produced lower levels of inflammatory cytokines compared to non-pregnant women. Our results suggest that B cells acquire a state of hypo-responsiveness during gestation, probably as part of the maternal immune strategy for fetal tolerance but also open new avenues to understand why pregnant women are at highest risk for infections.

Analysis of the Impact of Changes in Echo Signal Parameters on the Uncertainty of Distance Measurements in p-ToF Laser Rangefinders.

The article presents results of research on the influence of changes in parameters of the digitally recorded echo signals on the uncertainty of pulsed Time-of-Flight (p-ToF) laser distance measurements. The main objective of the study was to evaluate the distance calculation method developed by the authors. This method is based on the acquisition of the full-waveform of the echo pulse signal and approximation of its shape by the second-degree polynomial (we called it SDPA for short). To determine the pulse transit time and measure the distance, the position of the vertex of this parabola is sought. This position represents the maximum intensity of the incoming echo signal and is related to the round-trip propagation time of the laser pulse. In the presented work, measurement uncertainty was evaluated using simulation tests for various parameters of the echo pulse. All obtained results were used to formulate the general relationship between the measurement uncertainty of the SDPA algorithm and the parameters of the received echo signals. This formula extends the base knowledge in the domain of laser p-ToF distance measurements. It can be used to estimate the measurement uncertainty of a FW LiDAR at an early design stage. This greatly improves capabilities of analysis of expected performance of the device. It can also be implemented directly into the rangefinder's measurement algorithm to estimate the measurement uncertainty based on the emission of a single pulse rather than a series of pulses.

Maternal pre-pregnancy underweight as a risk factor for the offspring: Survey of Neonates in Pomerania.

AIM: The aim was to investigate socio-economic risk factors for maternal underweight before pregnancy and then associations of underweight with neonatal outcomes. METHODS: Data of 3401 mother-child dyads from the population-based birth cohort Survey of Neonates in Pomerania (SNiP) were analysed. RESULTS: Bivariate analysis showed that underweighted mothers were younger, smoked more often, had a lower equivalent income and lower socio-economic status (employment status and/or educational level) compared to women with normal weight. The final prediction model revealed that only younger maternal age (OR = 0.93; 95%-CI = 0.90-0.97) and maternal smoking during pregnancy (OR = 2.52; 95%-CI = 1.74-3.66) were associated with underweight. Compared to women with normal pre-pregnancy BMI, underweight women had an increased chance of premature labour (OR = 1.73; 95% CI: 1.29-2.31) and a reduced placental weight. The offspring of underweight women had an increased risk of late preterm birth (OR = 1.82; 95% CI: 1.21-2.74) and birthweight < 2500 g (OR = 1.91; 95% CI: 1.23-2.95). CONCLUSION: Smoking during pregnancy and a younger age were identified as risk factors for maternal pre-pregnancy underweight which then was associated with late preterm birth and low birthweight.

Methods of Precise Distance Measurements for Laser Rangefinders with Digital Acquisition of Signals.

The article presents methods of long range distance measurements using pulsed lasers and the Time of Flight principle. Various algorithms of laser distance measurements with digital acquisition of echo pulses (acquisition of a signal's full waveform) are presented. The main focus of work is concentrated on the method of distance measurements developed by the authors. With this method, during laboratory trials, a total measurement error of one centimeter was achieved using a 905 nm pulsed laser diode and pulse width of 39 ns. The maximum range of measurements with such high precision is limited only by a signal to noise ratio, duration of measurements and atmospheric conditions. All algorithms were implemented in a laser rangefinder module developed by the authors. Simulations and laboratory experiments were conducted and algorithm's accuracy and precision were tested for various SNR conditions and changing distances.

Distinguishing Drones from Birds in a UAV Searching Laser Scanner Based on Echo Depolarization Measurement.

Widespread availability of drones is associated with many new fascinating possibilities, which were reserved in the past for few. Unfortunately, this technology also has many negative consequences related to illegal activities (surveillance, smuggling). For this reason, particularly sensitive areas should be equipped with sensors capable of detecting the presence of even miniature drones from as far away as possible. A few techniques currently exist in this field; however, all have significant drawbacks. This study addresses a novel approach for small (<5 kg) drones detection technique based on a laser scanning and a method to discriminate UAVs from birds. The latter challenge is fundamental in minimizing the false alarm rate in each drone monitoring equipment. The paper describes the developed sensor and its performance in terms of drone vs. bird discrimination. The idea is based on simple cross-polarization ratio analysis of the optical echo received as a result of laser backscattering on the detected object. The obtained experimental results show that the proposed method does not always guarantee 100 percent discrimination efficiency, but provides certain confidence level distribution. Nevertheless, due to the hardware simplicity, this approach seems to be a valuable addition to the developed anti-drone laser scanner.

Pregnancy status alters IL-21-mediated effects on murine B lymphocytes.

A favorable outcome of pregnancy depends greatly on an adequate balance of immune protection and fetal tolerance at the fetomaternal interface. IL-21 is a pro-inflammatory cytokine associated with altering immune responses in autoimmune diseases. IL-21 has pleiotropic functions, including induction of Th17 T cells, inhibition of Treg development, and modulation of antibody responses of B lymphocytes. Genetic polymorphisms of IL21 have been associated to poor pregnancy outcomes. However, the mechanism of IL-21 actions needs further evaluation. Here, we postulate that IL-21 affects splenic B cell function during pregnancy and shapes immune responses. We show that splenic B cells from CBA/J × BALB/c mice with favorable pregnancy outcome expressed lower IL21R levels than in CBA/J × DBA/2J mice, a mouse model for immune-induced bad pregnancy outcome. As a consequence, B cells from CBA/J × BALB/c mice reacted less sensitively to IL-21 than B cells from non-pregnant mice (NPM) or from CBA/J × DBA/2J mice. Also, LPS-induced apoptotic rates were altered in NPM and CBA/J × DBA/2J but not in CBA/J × BALB/c mice. This is accompanied by improved survival of B cells that produce the anti-inflammatory cytokine IL-10 upon stimulation with LPS. We also observed lower numbers of CD4+CXCR5+Bcl-6+ follicular T-helper cells (Tfh) in normal pregnant mice, compared to non-pregnant and mice with disturbed pregnancies. Our data indicate that alterations of the Tfh/IL-21/IL-10 axis may have important influence on pregnancy outcome.

Hormonally controlled ILC antigen presentation potential is reduced during pregnancy.

Strategically located in mucosal barriers, innate lymphoid cells (ILCs) are relevant in local containment and tolerance of commensal microflora. ILCs have been recently described at the fetomaternal interface, where the development of a semi-allogeneic fetus can only succeed in a well-controlled immune environment. We postulate that ILCs adapt their antigen presentation capacity to protect pregnancy from excessive immune responses. Human ILCs were studied in deciduae of term pregnancies, peripheral blood and in in vitro generated ILCs. Fresh isolated lymphocytes or cells treated with pregnancy-related factors were investigated. The fetal antigen rejection-based CBA/J × DBA/2J mouse model (poor outcome pregnant mice; POPM) was used to characterize ILC antigen presentation potential in normal and immunologically disturbed pregnancies. ILC antigen presentation potential was characterized by flow cytometry and qPCR. We discovered that the distribution of ILC subsets changed during both human and murine pregnancy. Moreover, the pregnancy was accompanied by reduced MHCII expression in splenic ILCs during normal pregnancy (CBA/J × BALB/c; good outcome pregnant mice; GOPM) but increased in splenic and intestinal ILCs of CBA/J × DBA/2J mice. In vitro, splenic ILCs from pregnant mice increased MHCII expression after stimulation with IL-1ß and IL-23. In contrast, uterine ILCs displayed lower MHCII expression, which remained unchanged after stimulation. Finally, pregnancy-related factors and hormones present in the uterine environment reduced antigen presentation potential of human ILCs in vitro. Together, these data indicate that, during pregnancy, peripheral and especially uterine ILCs adapt their antigen presenting potential to maintain a level of tolerance and support pregnancy.

Survey of Neonates in Pomerania (SNiP): Study design and cohort update.

BACKGROUND: The health status of newborns is a major concern for parents and medical personnel. Recent studies have provided increasing evidence that factors from the foetal and perinatal periods of life influence health later in life. The "Follow-up of the Survey of Neonates in Pomerania" (SNiP-I-Follow-up) is the first follow-up of the population-based birth cohort study, SNiP-I, established in north-east Germany. OBJECTIVES: The primary aim of SNiP-I-Follow-up study was the collection of longitudinal data on children and adolescents. The associations will be analysed between risk factors in pregnancy and the perinatal period and health status in infancy and later childhood. POPULATION: The population-based cohort study SNiP-I was conducted in Pomerania in north-east Germany between February 2002 and November 2008. All mothers from the SNiP-I birth cohort were recontacted when their children were from 9 to 15 years of age. DESIGN: The SNiP-I-Follow-up study was carried out between December 2016 and August 2017 and is a questionnaire-based survey. METHODS: Physical development, health status, and social behaviour (school and leisure behaviour) of children were analysed using a questionnaire comprising medical, epidemiological, and socio-economic data, associated health care risk factors, and life circumstances of newborns, children, and their parents. PRELIMINARY RESULTS: Out of 5725 children invited to participate in the SNiP-I-Follow-up study between December 2016 and August 2017, 29% (n = 1665) children participated in the SNiP-I-Follow-up study, providing data on 1665 mothers-child dyads. Responders had higher socio-economic status, especially in relation to maternal education status. CONCLUSION: As a longitudinal birth cohort from rural Germany, the SNiP cohort will be a resource to address urgent research needs and contribute to overall population health.

Freeform Mirror Design for Novel Laser Warning Receivers and Laser Angle of Incidence Sensors.

In this paper, we present a novel configuration of an optical angle-of-incidence (AOI) sensor based on the application of a freeform mirror. The main challenge in designing this mirror was to provide a strictly linear transformation between AOI and the spatial position of the spot created on the linear detector array. Another two goals of this paper were to minimize stray light issues (improve the dynamic range) and create an intermediate focus and lateral shift in the detector position with respect to the plane of incidence. From an optical point of view, the designed mirror can thus be understood as the composition of three components: a high-numerical-aperture (NA) fully achromatic f-theta lens in one cross-section and a perfectly focusing lens, combined with a deviating prism in the second (orthogonal) cross-section. In comparison to the standard "shade" methods, the proposed approach allows a constant angular resolution to be maintained over the entire field of view. The mirror was designed on the basis of fundamental geometrical rules by numerically solving differential problems using an innovative scheme based on the minimization of the specific merit function. The proposed method was practically applied to design a freeform mirror for a 90°/120° field-of-view sensor, showing a satisfactory performance.

CD83 is locally regulated and differentially expressed in disturbed murine pregnancy.

Alterations in the immunologic balance during pregnancy have been associated with poor pregnancy outcomes. The underlying mechanisms are complex and mouse models delivered valuable information on inflammatory imbalance in disturbed pregnancies and served as model to test potential anti-inflammatory therapies. CD83 is a transmembrane protein (mCD83) with a soluble form (sCD83) which possesses strong anti-inflammatory properties. During murine pregnancy, upregulated mCD83 expression induces sCD83 release after in vitro stimulation with LPS, phorbol myristate acetate (PMA) and ionomycin. The release mechanism of sCD83 and its control are yet to be elucidated. In this study, the expression of mCD83 and sCD83 has been extensively studied in the CBA/J × DBA/2J mouse model of pro-inflammatory-mediated pregnancy disturbances. mCD83 was higher expressed on splenic B cells, uterus-draining lymph nodes T cells and dendritic cells from mice with poor pregnancy outcome (PPOM) compared to mice with good pregnancy outcome (GPOM). PPOM, however, was accompanied by lower sCD83 serum levels. In vitro treatment of splenic B cells with progesterone led to a reduction of TIMP1 expression, mCD83 expression and sCD83 release, while TIMP1 treatment had a positive effect on sCD83 availability. These results suggest that tissue and matrix components are involved in the regulation of CD83 in murine pro-inflammatory pregnancies.

Characterization of murine amniotic fluid B cells in normal pregnancy and in preterm birth.

The amniotic fluid provides mechanical protection and immune defense against pathogens to the fetus. Indeed, components of the innate and adaptive immunity, including B cells, have been described in the amniotic fluid. However, limited information concerning phenotype and functionality of amniotic fluid B cells is available. Hence, we aimed to perform a full phenotypical and functional characterization of amniotic fluid B cells in normal pregnancy and in a mouse model of preterm birth. Phenotypic analysis depicted the presence of two populations of amniotic fluid B cells: an immature population, resembling B1 progenitor cells and a more mature population. Further isolation and in vitro co-culture with a bone marrow stroma cell line demonstrated the capacity of the immature B cells to mature. This was further supported by spontaneous production of IgM, a feature of the B1 B cell sub-population. An additional in vitro stimulation with lipopolysaccharide induced the activation of amniotic fluid B cells as well as the production of pro and anti-inflammatory cytokines. Furthermore, amniotic fluid B cells were expanded in the acute phase of LPS-induced preterm birth. Overall our data add new insight not only on the phenotype and developmental stage of the amniotic fluid B1 B cells but especially on their functionality. This provides important information for a better understanding of their role within the amniotic fluid as immunological protective barrier, especially with regard to intraamniotic infection and preterm birth.

Oxytocin antagonism reverses the effects of high oestrogen levels and oxytocin on decidualization and cyclooxygenase activity in endometrial tissues.

RESEARCH QUESTION: What is the in-vitro effect of oxytocin receptor (OTR) antagonism on parameters of receptivity in human endometrial explants and endometrial stromal cell lines cultured in oestradiol-rich conditions mimicking ovarian stimulation? DESIGN: Experimental in-vitro study on endometrial tissue explants collected by aspiration biopsy from 30 women undergoing fertility treatment and cultured endometrial tHESC cell line. The study examined the effects of high oestradiol, oxytocin and OTR antagonist on parameters of decidualization (cell viability and prolactin secretion) as well as cyclooxygenase-1/2 (COX-1/2) activity and prostaglandin F2α (PGF2α) secretion. Changes in expression of OXTR and COX-2 genes were examined using quantitative polymerase chain reaction (qPCR). RESULTS: In experiments on cultured endometrial cell line, high oestradiol and oxytocin similarly limited the viability of cells. In cultured endometrial explants both also decreased the secretion of prolactin (a marker of decidualization) and augmented endometrial COX-2 activity and formation of PGF2α. Oxytocin antagonist atosiban was confirmed to reverse the above effects, both in the endometrial line and endometrial explants. Addition of atosiban to cultures acted analogously in experiments employing both oxytocin and high oestradiol. CONCLUSIONS: Oxytocin antagonist reversed the effects of high oestradiol and oxytocin on parameters related to endometrial receptivity in conditions mimicking ovarian stimulation. This might point to a novel, endometrium-related mechanism to support embryo implantation achieved by the application of oxytocin antagonist prior to embryo transfer.

Benign uterine mass-discrimination from leiomyosarcoma by a preoperative risk score: a multicenter cohort study.

PURPOSE: Discrimination of uterine leiomyosarcoma (LMS) and leiomyoma (LM) prior to surgery by basic preoperative characteristics and development of a preoperative leiomyosarcoma score. METHODS: A predominantly prospective cohort of 826 patients with LM from a clinical institution and an outpatient center was included in the study. Further a predominantly retrospective cohort of 293 patients with LMS was included from the counseling database of the German Clinical Center of Excellence for Genital Sarcoma and Mixed Tumors (DKSM, University Medicine Greifswald, Germany). We analyzed and compared anamnestic, epidemiological and clinical findings between both cohorts. Tenfold cross-validated logistic regression and random forest was performed on the 80% training set. The preoperative LMS score (pLMS) was developed based on logistic regression and independently evaluated by analyzing the area under the receiver operating characteristic curve (AUC) with the 20% test set. RESULTS: In the LMS cohort, 63.1% had initially surgery for presumed LM and only 39.6% of endometrial biopsies revealed LMS. Key features for LMS discrimination were found to be bleeding symptoms: intermenstrual bleeding [RRc = 2.71, CI = (1.90-3.49), p < 0.001], hypermenorrhea [RRc = 0.28, CI = (0.15-0.50), p < 0.001], dysmenorrhea [RRc = 0.22, CI = (0.10-0.51), p < 0.001], postmenstrual bleeding [RRc = 2.08, CI = (1.30-2.75), p < 0.001], suspicious sonography [RRc = 1.21, CI = (1.19-1.22), p < 0.001] and the tumor diameter (each centimeter difference: ß = 0.24, SD = 0.04, p < 0.001). pLMS achieved a mean cross-validated AUC of 0.969 (SD = 0.019) in the training set and an AUC of 0.968 in the test set. CONCLUSIONS: The presented score is based on basic clinical characteristics and allows the prediction of LMS prior to a planned surgery of a uterine mass. In case pLMS is between - 3 and + 1, we suggest subsequent diagnostics, such as endometrial biopsy, color Doppler sonography, LDH measurement, MRI and transcervical biopsy.

Evaluation of neonatal and maternal morbidity in mothers with gestational diabetes: a population-based study.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequent complication during pregnancy. Untreated GDM is a severe threat to maternal and neonatal health. Based on recent evidence, up to 15% of all pregnancies may be affected by GDM. We hypothesized that in a rural birth cohort, higher maternal BMI and adverse socioeconomic conditions would promote GDM, which in turn would lead to adverse effects on pregnancy outcomes. METHODS: The current study is a part of a population-based cohort study examining the health and socioeconomic information from 5801 mothers and their children. The study, titled the Survey of Neonates in Pomerania (SNiP), was based in northeastern Pomerania, Germany (2002-2008). RESULTS: The cumulative incidence of GDM was 5.1%. Multiple logistic regression revealed prepregnancy overweight (OR 1.84 (95% CI 1.27-2.68)), prepregnancy obesity (OR 3.67 (2.48-5.44)) and maternal age (OR 1.06 (1.03-1.08)) as risk factors for GDM (p = 0.001). Alcohol use during pregnancy (OR 0.61 (0.41-0.90), a higher monthly income (OR 0.62 (0.46-0.83)), and the highest level of education (OR 0.44 (0.46-0.83)) decreased the risk of GDM. Newborns of GDM mothers had an increased risk of hypoglycaemia (OR 11.71 (7.49-18.30)) or macrosomia (OR 2.43 (1.41-4.18)) and were more often delivered by primary (OR 1.76 (1.21-2.60)) or secondary C-section (OR 2.00 (1.35-2.97)). Moreover, they were born 0.78 weeks (95% CI -1.09 - -0.48 weeks) earlier than infants of mothers without diabetes, resulting in higher percentage of late preterm infants with a gestational age of 32-36 weeks (11.1% vs. 6.96%). CONCLUSIONS: Age and BMI before pregnancy were the predominant mediators of the increased risk of GDM, whereas a higher income and educational level were protective. GDM affected relevant perinatal and neonatal outcomes based on its association with an increased risk of delivery by C-section, preterm birth, macrosomia at birth and neonatal hypoglycaemia.

Stimulation of chemokines in human endometrial stromal cells by tumor necrosis factor-α and interferon-γ is similar under apoptotic and non-apoptotic conditions.

PURPOSE: Tumor necrosis factor (TNF)-α and interferon (IFN)-γ are pro-inflammatory cytokines which have been shown to be involved in the pathophysiology of implantation disorders. Both cytokines in combination are able to sensitize primarily resistant human endometrial stromal cells (ESCs) to Fas-induced apoptosis. Since CCL (CC-chemokine ligand) 5 and CCL2 are important regulators of the endometrial immune cell population, we examined the impact of TNF-α and IFN-γ on these two chemokines under non-apoptotic and apoptotic conditions. METHODS: ESCs were isolated from hysterectomy specimens, decidualized in vitro and incubated with TNF-α, IFN-γ, an activating anti-Fas antibody and a caspase-inhibitor. CCL5 and CCL2 were measured using ELISA and real-time RT-PCR. Apoptosis was determined by flow cytometry, and cellular viability and membrane integrity were measured by fluorescent assays. RESULTS: The secretion of CCL5 and CCL2 was stimulated in undifferentiated and decidualized ESCs by the combination of TNF-α and IFN-γ under non-apoptotic as well as apoptotic (with Fas-stimulation in parallel) conditions. TNF-α or IFN-γ alone did not have this effect. The stimulatory influence of TNF-α plus IFN-γ on CCL5 and CCL2 in ESCs was also seen on the transcriptional level. Inhibition of cell death by a caspase-inhibitor had no influence on the secretion of CCL5 and CCL2 in ESCs under apoptotic stimulation. CONCLUSION: TNF-α and IFN-γ modulate the secretion of chemokines in ESCs independently of Fas-induced apoptosis. These results suggest a constant response pattern on pro-inflammatory cytokines within the population of human ESCs.

Clinical Outcome of Neoadjuvant Radiochemotherapy in Locally Advanced Cervical Cancer: Results of an Open Prospective, Multicenter Phase 2 Study of the North-Eastern German Society of Gynecological Oncology.

OBJECTIVE: The aim of this study was to determine the response rate, toxicity, operability, and surgical complication rate of neoadjuvant concomitant radiochemotherapy (cRCH) (ifosfamide + carboplatin) followed by radical hysterectomy plus external-beam radiotherapy with curative intention in locally advanced primary inoperable stages IIB and IIIB squamous cell cervical cancer. METHODS: Patients with cervical cancer from 8 departments were enrolled. Patients received 3 cycles of ifosfamide 1.2 mg/m (+mesna 20%) plus carboplatin (area under the curve = 4), every 21 days, and concomitant external-beam radiotherapy (50.4 Gy [1.8 Gy/d]). Operability and remission were evaluated by clinical gynecological examination in general anesthesia (magnetic resonance imaging was optional), 4 weeks after the third cycle of cRCH. In case of achieved operability, a radical hysterectomy with pelvic lymphadenectomy was performed within 6 weeks after cRCH. If surgery was not performed because of incomplete remission or patient preferences, vaginal brachytherapy (15 Gy [5 Gy/d]) was given additionally. RESULTS: Forty-four patients were enrolled. Distribution of FIGO (International Federation of Gynecology and Obstetrics) tumor stage was as follows: IIB (19 patients) and IIIB (25 patients). All patients completed cRCH. Grade 3/4 hematologic toxicities (% of all cycles) were moderate: leukopenia, 7.3; thrombocytopenia, 2.4; and anemia, 3.2. In 13.8%, treatment cycles were delayed because of hematologic toxicity. Blood transfusions were given in 17.7% and granulocyte colony-stimulating factor in 39.5%. Overall, grade 3/4 nonhematologic toxicities were seldom (6.5%). Clinical overall response rate was 95.2%. Operability was achieved in 85.7%. Surgery was performed in 83.3%. Pathological response rates were as follows: pathological complete remission, 33.3%; partial remission, 63.3%; stable disease, 3.3%. CONCLUSIONS: Our study demonstrates that cRCH is an effective and tolerable regimen in locally advanced cervical cancer treatment.