Functional Heterogeneity of Umbilical Cord Blood Monocyte-Derived Dendritic Cells.

Human umbilical cord blood (UCB) represents a unique resource for hematopoietic stem cell transplantation for children and patients lacking suitable donors. UCB harbors a diverse set of leukocytes such as professional APCs, including monocytes, that could act as a novel source for cellular therapies. However, the immunological properties of UCB monocytes and monocyte-derived dendritic cells (MoDCs) are not fully characterized. In this study, we characterized the phenotype and functions of UCB-MoDCs to gauge their potential for future applications. UCB exhibited higher frequencies of platelets and lymphocytes as well as lower frequencies of neutrophils in comparison with adult whole blood. Leukocyte subset evaluation revealed significantly lower frequencies of granulocytes, NK cells, and CD14+CD16- monocytes. Surface marker evaluation revealed significantly lower rates of costimulatory molecules CD80 and CD83 while chemokine receptors CCR7 and CXCR4, as well as markers for Ag presentation, were similarly expressed. UCB-MoDCs were sensitive to TLR1-9 stimulation and presented quantitative differences in the release of proinflammatory cytokines. UCB-MoDCs presented functional CCR7-, CXCR4-, and CCR5-associated migratory behavior as well as adequate receptor- and micropinocytosis-mediated Ag uptake. When cocultured with allogeneic T lymphocytes, UCB-MoDCs induced weak CD4+ T lymphocyte proliferation, CD71 expression, and release of IFN-γ and IL-2. Taken together, UCB-MoDCs present potentially advantageous properties for future medical applications.

Feasibility and Satisfaction With the Word Catheter in Treatment of Bartholin's Cyst and Abscess.

BACKGROUND/AIM: The Word catheter is a silicone device with a balloon system that may be inserted into a Bartholin's cyst or abscess in order to provide drainage and epithelization. The aim of this study was to evaluate the Word catheter as a therapy for Bartholin's cyst and abscess. Both patient and physician satisfaction, as well as the feasibility in an outpatient setting, were examined. PATIENTS AND METHODS: A total of 51 women with a Bartholin's cyst or abscess were given the option of Word catheter insertion in an outpatient setting between August 2013 and March 2018. Both the patients and the consulting physicians were asked to complete two questionnaires, before, during and after treatment, with a view to evaluating the overall pain level, any discomfort symptoms and sexual activity, as well as satisfaction levels. RESULTS: The insertion procedure seemed to constitute a short yet quite painful procedure. In most cases, the consulting physicians and the patients were content with the results. Nevertheless, dislodgement of the catheter or abscess recurrence were common. The removal of the Word catheter seemed to be short, painless, and uncomplicated. Most patients experienced pain and discomfort after catheter placement over the first days, with the symptoms fading over time. Sexual intercourse appeared to be negatively influenced. CONCLUSION: The Word catheter was frequently well tolerated for the treatment of Bartholin's cysts and abscesses, with few non-serious side-effects, however, it did interfere with sexual health. Nonetheless, it may not be possible to make general recommendations based on this exploratory study.

The use of PAMG-1 testing in patients with preterm labor, intact membranes and a short sonographic cervix reduces the rate of unnecessary antenatal glucocorticoid administration.

OBJECTIVES: To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination. METHODS: Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks' gestation, rate of admission to neonatal intensive care unit (NICU). RESULTS: In total, 130 cases were included. "PAMG-1 group" consisted of 68 women, 62 cases built the "historical control group". ACS administration was performed less frequently in the "PAMG-1 cohort" (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks' gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks' gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the "historical control group" (22 (38%) vs. 28 (60%); p=0.0272). CONCLUSIONS: Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length.

Influence of labor on direct and indirect determinants of placental 11beta-hydroxysteroid dehydrogenase activity.

PURPOSE: Labor is a complex process involving multiple para-, auto- and endocrine cascades. The interaction of cortisol, corticotropin-releasing hormone (CRH) and progesterone is essential. The action of cortisol on the human feto-placental unit is regulated by 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2/HSD11B2) that converts cortisol into inactive cortisone. The majority of studies on the assessment of placental 11ß-HSD2 function determined indirect activity parameters. It remains elusive if indirect measurements correlate with enzymatic function and if these parameters are affected by potential confounders (e.g., mode of delivery). Thus, we compared determinants of indirect 11ß-HSD2 tissue activity with its direct enzymatic turnover rate in placental samples from spontaneous births and cesarean (C)-sections. METHODS: Using LC-MS/MS, we determined CRH, cortisol, cortisone, progesterone and 17-hydroxy(OH)-progesterone in human term placentas (spontaneous birth vs. C-section, n = 5 each) and measured the enzymatic glucocorticoid conversion rates in placental microsomes. Expression of HSD11B1, 2 and CRH was determined via qRT-PCR in the same samples. RESULTS: Cortisol-cortisone ratio correlated with direct microsomal enzymatic turnover. While this observation seemed independent of sampling site, a strong influence of mode of delivery on tissue steroids was observed. The mRNA expression of HSD11B2 correlated with indirect and direct cortisol turnover rates in C-section placentas only. In contrast to C-sections, CRH, cortisol and cortisone levels were significantly increased in placental samples following spontaneous birth. CONCLUSION: Labor involves a series of complex hormonal processes including activation of placental CRH and glucocorticoid metabolism. This has to be taken into account when selecting human cohorts for comparative analysis of placental steroids.

Maintenance tocolysis: a reappraisal of clinical evidence.

INTRODUCTION: Maintenance tocolysis, mostly defined as the continuation of tocolytic treatment beyond 48 h, remains a matter of debate. There is no sufficient evidence from randomized controlled trials, that maintenance tocolysis is able to prolong pregnancy significantly and to reduce severe neonatal morbidity and mortality. Hence, it is not recommended in current guidelines. On the contrary, maintenance tocolysis is commonly used in clinical practice and subject of current clinical-scientific investigations. TOCOLYTICS FOR MAINTENANCE TREATMENT: None of the conventional tocolytics (beta-sympathomimetics, calcium-channel blockers, magnesium, cyclooxygenase inhibitors, and oxytocin receptor antagonists) have proven to be appropriate for maintenance treatment. Progesterone and 17-α-hydroxyprogesterone caproate have shown promising results in low-quality randomized trials, but not in high-quality studies. DISCUSSION: Basically, the value of studies regarding maintenance tocolysis is limited by a considerable heterogeneity, its mostly low quality, significant differences in methodology as well as the inadequate statistical power due to the small number of women studied. So far, maintenance tocolysis is a case-by-case decision outweighing the benefits and harms of tocolytic treatment.

Accuracy of colposcopy-directed biopsy in detecting early cervical neoplasia: a retrospective study.

PURPOSE: Colposcopy-directed biopsy is a cornerstone method for diagnosing cervical intraepithelial neoplasia. The aim of this study was to evaluate the accuracy of colposcopy-directed biopsy in comparison with definitive surgery. METHODS: The accuracy of colposcopy-directed biopsy was compared with the final histology in relation to different types of transformation zone (TZ), the patient's age, and the examiner's level of training. RESULTS: The overall accuracy of biopsy in comparison with definitive surgery was 71.9% for all entities-benign lesions, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and cervical carcinoma-with an underdiagnosis rate of 11.8% and an overdiagnosis rate of 16.5%. The accuracy for detecting HSIL was 88% (401/455), with an underdiagnosis rate of 10.5% and overdiagnosis rate of 1.3%. The accuracy rates for detecting HSIL in women with TZ 1, TZ 2, or TZ 3 were 92.2, 90.5, and 76.5%, respectively. The accuracy rates for detecting HSIL in the different age groups were 93.1% (age 0-34), 83.6% (age 34-55), and 80% (age 55 or older). CONCLUSIONS: A combination of the colposcopic findings, cytology, human papillomavirus testing, and colposcopy-directed biopsy is necessary for the correct diagnosis of HSIL. The accuracy rate depends on the TZ and the patient's age. The examiner's level of training does not have any substantial influence on the accuracy.

Predicting attention deficit hyperactivity disorder using pregnancy and birth characteristics.

PURPOSE: The aim of this study was to evaluate maternal, prenatal, perinatal, and postpartum parameters as risk factors for the later development of an attention deficit hyperactivity disorder (ADHD) in the child. METHODS: Women who had given birth at Erlangen University Hospital between 1996 and 1999 were sent a questionnaire in 2009. The results of the questionnaire were correlated with the prospectively collected data for the births in 1996-1999. RESULTS: A total of 573 mother and child pairs were analyzed. Forty-four of the mothers reported that their child had ADHD (7.7%). No significant associations were found for the following parameters: mother's age; mother's educational level; number of the pregnancy; maternal weight before and at the end of pregnancy; mother's height; alcohol consumption during pregnancy; mode of delivery; gestational week; birthweight; umbilical artery blood values; Apgar score at 5 and 10 min; or breastfeeding. The parameters of smoking in pregnancy and an Apgar score lower than 7 after 1 min were significantly associated with a risk for later development of ADHD. CONCLUSIONS: This analysis of maternal, prenatal, perinatal, and postnatal parameters found that smoking in pregnancy and a low Apgar score 1 min after birth are associated with a significantly greater risk for the development of ADHD. Beyond the question of the causal mechanism involved, this is a relevant finding, since smoking during pregnancy is a preventable risk factor.

Trophoblast expression dynamics of the tumor suppressor gene gastrokine 2.

Gastrokines (GKNs) were originally described as stomach-specific tumor suppressor genes. Recently, we identified GKN1 in extravillous trophoblasts (EVT) of human placenta. GKN1 treatment reduced the migration of the trophoblast cell line JEG-3. GKN2 is known to inhibit the proliferation, migration and invasion of gastric cancer cells and may interact with GKN1. Recently, GKN2 was detected in the placental yolk sac of mice. We therefore aimed to further characterize placental GKN2 expression. By immunohistochemistry, healthy first-trimester placenta showed ubiquitous staining for GKN2 at its early gestational stage. At later gestational stages, a more differentiated expression pattern in EVT and villous cytotrophoblasts became evident. In healthy third-trimester placenta, only EVT retained strong GKN2 immunoreactivity. In contrast, HELLP placentas showed a tendency of increased levels of GKN2 expression with a more prominent GKN2 staining in their syncytiotrophoblast. Choriocarcinoma cell lines did not express GKN2. Besides its trophoblastic expression, we found human GKN2 in fibrotic villi, in amniotic membrane and umbilical cord. GKN2 co-localized with smooth muscle actin in villous myofibroblasts and with HLA-G and GKN1 in EVT. In the rodent placenta, GKN2 was specifically located in the spongiotrophoblast layer. Thus, the gestational age-dependent and compartment-specific expression pattern of GKN2 points to a role for placental development. The syncytial expression of GKN2 in HELLP placentas might represent a reduced state of functional differentiation of the syncytiotrophoblast. Moreover, the specific GKN2 expression in the rodent spongiotrophoblast layer (equivalent to human EVT) might suggest an important role in EVT physiology.

Touch imprint cytology of core needle biopsy specimens for the breast and quick stain procedure for immediate diagnosis.

AIM: To investigate the validity and reproducibility of touch imprint cytology (TIC) of core needle biopsies (CNBs) in the assessment of conspicuous breast findings. MATERIALS AND METHODS: One hundred and fifty-eight conspicuous breast findings were assessed by CNB during a two-year period in this prospective study. TIC of the CNBs was used for cytological analysis. The performance of this technique was evaluated by comparing the results with the histology of the CNB, and in cases of a subsequent surgery, with the final histology. In addition, inter-observer reproducibility was analyzed. RESULTS: The inter-observer variability was very high (kappa-value of 0.8508; excluding inadequate imprints, 0.9502). Inadequate cellularity for cytological analysis was found in 11.4% (18/158) of findings. Compared with CNB histology, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of TIC was 99%, 100%, 100%, 94%, and 99%, respectively. CONCLUSION: TIC of CNB specimens of the breast may be a valid option for providing a diagnosis without delay for a histological procedure, assuming good quality of the specimen.

Influence of age on short-term complications after intraoperative radiotherapy in women after breast-conserving surgery.

BACKGROUND: We investigated the influence of age on short-term complications in women undergoing intraoperative radiotherapy (IORT) for early breast cancer. PATIENTS AND METHODS: We retrospectively analyzed data of 188 women who underwent IORT during breast-conserving surgery (BCS). The study group consisted of 54 patients aged 70 years or older. One hundred and thirty four patients aged less than 70 years served as the control group. RESULTS: In both collectives, the acute toxicity was low. There were no significant differences regarding type and duration of surgery, and type of radiation treatment, comparing both collectives. The most frequent postoperative side-effects were haematoma/suggillation (13/54, 24.1% vs. 28/134, 20.9%; p=0.633). There was a significantly higher incidence of postoperative axillary haematoma in the study group (10/54, 18.5% vs. 10/134, 7.5%; p=0.026). CONCLUSION: Acute toxicity after BCS with IORT in women aged 70 years and older does not seem to be higher compared to younger patients.

Laparoscopic supracervical hysterectomy with concomitant bilateral salpingectomy--why not?

AIM: The aim of this investigation was to analyze the feasibility and postoperative outcome of laparoscopic supracervical hysterectomy (LASH) with and without bilateral salpingectomy. PATIENTS AND METHODS: Between February and October 2012, a total of 25 patients were prospectively enrolled to undergo LASH with bilateral salpingectomy. A retrospective cohort of 25 matched patients who underwent LASH without bilateral salpingectomy at our Institution, performed by the same surgeon, served as the control collective. RESULTS: Comparing both collectives, there were no statistically significant differences concerning overall hospital stay, duration of surgery and blood loss. CONCLUSION: LASH with bilateral salpingectomy is a fast and safe procedure.

Clinical aspects of intraoperative radiotherapy in early breast cancer: short-term complications after IORT in women treated with low energy x-rays.

BACKGROUND: To assess postoperative complications, clinical outcome and histological findings in patients undergoing intraoperative radiotherapy with low energy x-rays for early breast cancer. METHODS: We retrospectively analysed data of 208 women who underwent intraoperative irradiation during breast conserving surgery (BCS) between 2002 and 2007. Demographic, clinical and surgical parameters as well as short-term complications within the first postoperative week and histological findings were evaluated. Toxicities were assessed using the CTC/EORTC Score. RESULTS: Postoperative complications were rare and the immediate toxicity low, without any grade 3/4 acute toxicity. The most frequent postoperative side effects were suggillation (24%) and palpable seroma (17.3%). In 78.6% of the axillary seroma and in 25% of the breast seroma a needle aspiration was inevitable. Erythema grade I-II of the breast was found in 27 women (13%); whereas in 7 patients (3.4%), mastitis was confirmed. In 57.7% of the cases, the pathological assessment revealed ductal invasive breast cancer and tumour size ranged between 0.1 and 4.5 cm (mean = 1.6 cm). CONCLUSION: IORT using Intrabeam® during BCS is safe, although it is associated with postoperative adverse events such as seroma. These should be mentioned and explained to women in detail during the preoperative discussion. This explicitly clinical description is useful for daily clinical practice; especially for giving a detailed analysis of the postoperative side effects during preoperative counselling.

Influence of overweight in elderly patients undergoing vaginal surgery due to pelvic floor disorders.

AIM: To evaluate the feasibility and safety of vaginal surgery for treatment of genital prolapse in overweight compared to normal weight patients aged 50 years or older. PATIENTS AND METHODS: We retrospectively reviewed the perioperative data of 93 patients aged between 50 and 87 years undergoing surgery due to pelvic floor disorders. A total of 54 women had a body mass index (BMI) of 25 kg/m(2) or higher and were defined as the study collective. Thirty-nine patients undergoing similar surgical procedures during the same period of time had a BMI less than 25 kg/m(2) and served as the control group. Operating time, duration of hospital stay, intra- and postoperative complications were evaluated as comorbidities. χ(2)-test, Fisher's exact test, Student's t-test and non-parametric Mann-Whitney U-test were applied to compare the results of both collectives. RESULTS: There were no significant differences between study and control collectives regarding time of surgery, duration of hospital stay or intra- and postoperative complications, although a significant difference was found with regard to the prevalence of pre-existing diabetes mellitus (17% in the study group, versus 5% in the control group, respectively, Fisher's exact test: p=0.04). CONCLUSION: Overweight in elderly patients undergoing vaginal surgery due to pelvic floor disorders does not affect the perioperative outcome and is not a risk factor for perioperative complications.

Spontaneous uterine rupture at the 21st week of gestation caused by placenta percreta.

PURPOSE: To describe the management of a ruptured uterus caused by placenta percreta in the 21st week of gestation. METHODS: We present a case report of a 33-year-old patient with a ruptured uterus in the 21st week of gestation who presented at the Department of Gynecology and Obstetrics, University of Schleswig-Holstein, Campus Luebeck. Therapeutic management was performed by laparoscopy, and consecutive laparotomy and hysterectomy. RESULTS: A 33-year-old patient presented with severe abdominal pain in the 21st week of gestation at the department of abdominal surgery. A laparoscopy was performed to exclude appendicitis. There was about one liter of blood in the peritoneal cavity and a small, bleeding lesion in the fundus uteri was found which was coagulated. The blood was evacuated and the patient returned to department of gynecology. One hour after the first operation, the patient developed signs of hypovolemic shock and ultrasound showed absent fetal heart beat. An immediate laparotomy was performed and a ruptured uterus was detected. The fetus was removed and a hysterectomy performed. Pathology results showed a placenta percreta. After a few days in hospital and transfusion of 4 liters of blood the patient was discharged in a healthy condition. CONCLUSIONS: In a pregnant woman with severe abdominal pain even in the 21st week of gestation a placenta percreta has to be considered as a differential diagnosis. If there is no evidence of other causes, laparoscopy may help to confirm the diagnosis and hysterectomy is a life saving intervention.