[Influence of Fetomaternal Risk Factors on Mortality and Morbidity in Extremely Preterm Infants]. / Einfluss von fetomaternalen Risikofaktoren auf die Mortalität und Morbidität von Extremfrühgeborenen.

INTRODUCTION: The management of pregnant women at risk of preterm delivery poses a challenge to the interdisciplinary team. At the edge of viability, it is crucial to take into consideration maternal and fetal risk factors when determining individual counseling and therapeutic approaches. METHODS: At a level 4 perinatal center, all preterm infants (PI) born in the years 2017 to 2020 who had a gestational age between 230/7 and 246/7 weeks and were cared for with a curative therapeutic approach were enrolled in a retrospective observational study. Divided into two groups (230/7-236/7 and 240/7-246/7 weeks of gestation), the PI were compared in terms of mortality and morbidity based on maternal and fetal risk factors. Thirteen risk factors and their prognostic relevance for survival were analyzed. RESULTS: 41 mothers with 48 PI were included. 9 neonates received primary palliative treatment and were excluded from the analyses. The survival rates between the two groups (n=21, n=27) showed no significant difference (66.7% versus 74.1%, p=0.750). A significantly higher mortality was observed in PI with an increased number of risk factors (p=0.004), the most severe of which were hypertensive disorders of pregnancy and preterm premature rupture of membranes. Data regarding morbidity showed no significant difference. CONCLUSION: Data regarding mortality correlate with national findings. Observed morbidity in the study population was recorded. The prediction of probability of survival is more precise when risk factors are taken into consideration.

Anxiety in caregiving partners of breast cancer patients.

PURPOSE: The aim of the present study was to determine the levels of anxiety of partners of breast cancer patients and to evaluate the differences of anxiety levels between patients and partners according to the stage of treatment, age and education level. METHODS: 57 spouses or domestic partners of breast cancer patients and 148 breast cancer patients participated in this prospective cohort study and filled out the questionnaires including the Spielberger state-trait-anxiety-inventory, as well as questions based on stress-triggering procedures during breast cancer diagnosis and therapy. RESULTS: State anxiety levels of partners were highest in partners who accompanied their patients when presenting for examinations and operations and tumorboard decisions (Mean State-Scores 52, 45 and 46.5). Anxiety scores were lowest at the stage of ongoing chemotherapy or follow-up. The 25% quartile of partners with the highest state anxiety levels had a significantly higher educational level (p = 0.023). Young men aged 18-35 years showed the highest levels of both trait and state anxiety. Partners showed significantly higher levels of anxiety than the patients for anesthetic complications (p < 0.001), e.g., fear of not waking up from general anesthetic and postoperative pain (p < 0.001). Patients showed significantly higher levels of anxiety for hairloss (p < 0.001), weight gain during chemotherapy (p < 0.001) and postoperative scars (p = 0.027). CONCLUSION: Breast cancer patients are much more concerned about body image issues than their male partners. As these body image-associated concerns often arise from the fear of loosing attraction to their partner, these fears might be reduced by speaking about them openly. Partners are mostly concerned about surgery and anesthetic-related complications. Therefore, preoperative medical information to the partner is mandatory. Partners of breast cancer patients should be included in psycho-oncological support and medical briefings. Probably high anxiety levels of both partners and patients should be taken into account (due to younger age, lower educational level and procedures causing distress). These partners and patients should receive extra careful (clarification) counselling and (treatment support such as a psycho-oncologist) involvement of a psyco-oncologist.

Treatment anxiety in breast cancer patients.

INTRODUCTION: The aim of the present study was to determine and evaluate the levels of anxiety of breast cancer patients according to the state of treatment, age and education level, as well as the anxiety potential of certain procedures during breast cancer treatment. METHOD: 148 breast cancer patients participated in this prospective cohort study and filled out the questionnaires including the Spielberger state-trait-anxiety-inventory, as well as questions based to stress triggering procedures during breast cancer therapy. The testing was accomplished with the Mann-Whitney U test, the significance level was set to 0.05. RESULTS: Patients who appeared for tumor board decision showed the highest state-anxiety levels (55.79 SD ± 18.73) followed by patients undergoing surgery (50.24 SD ± 13.84). Patients already undergoing chemotherapy had lower state-anxiety levels than the group of all other patients (p = 0.012). Women undergoing chemotherapy showed lower anxiety levels relating to many procedures of breast cancer treatment. The 25% quartile of patients with the highest levels in the trait score showed a significant poorer education level (p = 0.009). Age showed no statistical influence on the anxiety level of breast cancer patients.  CONCLUSION: Patients with probably high anxiety levels (younger age, low education level, and those appearing for frightening procedures) should receive extra careful clarification and treatment support such as a psycho-oncologist.

Power Doppler flow mapping and four-dimensional ultrasound for evaluating tubal patency compared with laparoscopy.

OBJECTIVES: To study the accuracy of four-dimensional (4D) ultrasound and power Doppler flow mapping in detecting tubal patency in women with sub-/infertility, and compare it with laparoscopy and chromopertubation. STUDY DESIGN: A prospective study. The study was performed in the outpatient clinic and infertility unit of a university hospital. The sonographic team and laparoscopic team were blinded to the results of each other. Women aged younger than 43 years seeking medical advice due to primary or secondary infertility and who planned to have a diagnostic laparoscopy performed, were recruited to the study after signing an informed consent. All of the recruited patients had power Doppler flow mapping and 4D hysterosalpingo-sonography by injecting sterile saline into the fallopian tubes 1 day before surgery. Registering Doppler signals, while using power Doppler, both at the tubal ostia and fimbrial end and the ability to demonstrate the course of the tube especially the isthmus and fimbrial end, while using 4D mode, was considered a patent tube. RESULTS: Out of 50 recruited patients, 33 women had bilateral patent tubes and five had unilateral patent tubes as shown by chromopertubation during diagnostic laparoscopy. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for two-dimensional power Doppler hysterosalpingography were 94.4%, 100%, 100%, 89.2%, and 96.2%, respectively and for 4D ultrasound were 70.4%, 100%, 100%, 70.4%, and 82.6%, respectively. CONCLUSIONS: Four-dimensional saline hysterosalpingography has acceptable accuracy in detecting tubal patency, but is surpassed by power Doppler saline hysterosalpingography. Power Doppler saline hysterosalpingography could be incorporated into the routine sub-/infertility workup.

Hantavirus infections by Puumala or Dobrava-Belgrade virus in pregnant women.

BACKGROUND: Hantavirus infection in humans usually occurs via inhalation of infectious aerosolized excreta of rodents. Horizontal human-to-human transmission was reported only for the highly virulent Andes virus. The likelihood of vertical transmission and the clinical outcome of hantavirus infections in pregnancy is still unpredictable. OBJECTIVES: Very few data were published about the impact of hantaviruses in pregnancy. Here we present four cases of pregnant women infected by European hantaviruses. The risk of vertical virus transmission was investigated. STUDY DESIGN: Four pregnant women with clinical signs of acute hantavirus disease were investigated for hantavirus IgM and IgG after onset of clinical symptoms. Furthermore, the newborns were tested for presence of viral RNA and antibodies in cord blood and, if any parameter was found positive, 8-12 months after delivery. RESULTS: Four women suffered from a hantavirus infection, two of them due to infection by Puumala virus and two by Dobrava-Belgrade virus. Three women delivered healthy babies by vaginal route and one woman by Caesarean section (week 28). In no case hantavirus RNA was detected in cord blood after delivery or in the 8-12 month old babies. Hantavirus IgG was detectable in the cord blood of 3 babies (but not in the preterm child); these antibodies disappeared after 8-12 months indicating a passive transfer of immunoglobulins. No child had any clinical sign of hantavirus infection. CONCLUSIONS: In this study, the absence of vertical hantavirus transmission was demonstrated for pregnant women with onset of hantavirus disease between gestation weeks 14 and 28.

Obesity decreases the chance to deliver spontaneously.

PURPOSE: To evaluate the impact of maternal obesity on labour, intrapartual assessment and delivery. METHODS: Retrospective cohort analysis of n = 11,681 deliveries supervised between 01 January 2000 and 31 December 2009. Results were analysed dividing the patients into two main groups according to their body mass index (BMI): group 1, control: BMI 18-24.9 and group 2 BMI, test >25. Subgroups were built: (0) BMI 25-29.9, (I) BMI 30-34.9, (II) BMI 35-39.9, (III) BMI >40. Exclusion criteria were defined as: delivery <37 + 0 weeks p.m., multiple pregnancy, comorbidity other than GDM, abnormal presentation, BMI <18.5, and incomplete data. The main outcome parameter was defined as secondary caesarean delivery rate and mode of delivery. RESULTS: N = 8,379 patients met the inclusion criteria and were divided in two groups: 1, n = 4,464 patients and 2, n = 3,915. Basic maternal characteristics including foetal vital parameters were equal in all groups. GDM occurred more frequently in obese patients (P < 0.001). For the main outcome parameter a significant decrease in the rate of spontaneous delivery between control/test groups (72-66%, P < 0.001) and control/I-III groups (72 vs. 50%, P < 0.001) could be observed. The rate of secondary c-section increased significantly according to a higher BMI (>40: OR 2.5, 95% CI 1.84-3.61, χ (2) P < 0.001). The groups showed no difference in the rate of injuries during delivery though foetal birth weight increased significantly with a higher BMI (3,412-3,681 g; P < 0.001). CONCLUSION: Obesity decreases the chance to deliver spontaneously. Moreover, the obese patient suffers from a significantly longer trial of labour (7.9 vs. 9.5 h) and an elevated risk of surgical delivery.

Quercetin-induced induction of the NO/cGMP pathway depends on Ca2+-activated K+ channel-induced hyperpolarization-mediated Ca2+-entry into cultured human endothelial cells.

Quercetin is one of the dietary-derived flavonoids that are held responsible for the beneficial effects of red wine drinking in coronary artery disease known as the "French paradox". We examined whether quercetin modulates endothelial function by influencing Ca2+-activated K+ channels with large conductance (BK(Ca)) in cultured human endothelial cells. Membrane potential and intracellular Ca2+ concentrations of cultured human endothelial cells derived from umbilical cord veins (HUVEC) were measured using the fluorescence dyes DiBAC, and FURA-2, respectively. NO production was examined using a cGMP radioimmunoassay. HUVEC proliferation was analyzed by cell counts and thymidine incorporation. A dose-dependent hyperpolarization of HUVEC was recorded when quercetin was added (5-100 micromol/L). The maximum effect (50 micromol/L) was significantly reduced by the addition of the highly selective BK(Ca) inhibitor iberiotoxin (100 nmol/L), but not by blockers of other Ca2+-activated K+ channels (n = 30; p < 0.05). This BK(Ca)-induced hyperpolarization caused a transmembrane Ca2+ influx, because the quercetin-induced increase of intracellular Ca2+ was blocked by iberiotoxin, or by applying 2-aminoethoxydiphenylborate (100 micromol/L)--an inhibitor of capacitative Ca2+ entry (n = 30; p < 0.05). Quercetin-induced cGMP levels were significantly reduced by the eNOS-inhibitor l-NMMA (300 micromol/L), and by iberiotoxin (n = 10; p < 0.05). Endothelial proliferation was significantly reduced by 56 % when cells were incubated with quercetin (n = 12; p < 0.05). This effect was due to the increased NO production, because it was reversed when the cells were treated with a combination of quercetin and l-NMMA. In conclusion quercetin improves endothelial dysfunction by increasing NO synthesis involving BK(Ca)-dependent membrane hyperpolarization-induced capacitative Ca 2+ entry. Increased NO production is responsible for the quercetin-dependent inhibition of endothelial proliferation.

The K+-channel opener NS1619 increases endothelial NO-synthesis involving p42/p44 MAP-kinase.

Ca(2+)-activated K(+) channels with large conductance (BK(Ca)) have been shown to play an important role in the regulation of vascular tone. We examined the role of the p42/p44 MAP-kinase (p42/p44(MAPK)) on nitric oxide (NO) production in human endothelial cells induced by the BK(Ca)-opener NS1619. Using DiBAC-fluorescence imaging a concentration-dependent (2.5-12.5 microM) hyperpolarization induced by NS1619 was observed. A significant increase of intracellular Ca(2+)-concentration by NS1619 was seen using Fura-2-fluorescence-imaging, which was blocked by 2-APB, or reduction of extracellular Ca(2+) (n=30; p<0.05). A cGMP-radioimmunoassay was used to examine NO synthesis. NS1619 significantly increased cGMP levels which was inhibited by LNMMA, iberiotoxin, BAPTA, 2-APB, reduction of extracellular Ca(2+), PD 98059, or U0126 (cGMP (pmol/mg protein): NS1619 3.25 +/- 0.85; NS1619 + L-NMMA 0.86 +/- 0.02; NS1619 + iberiotoxin 0.99 +/- 0.09; NS1619 + BAPTA 0.93 +/- 0.29; NS1619 + 2-APB 0.99 +/- 0.31; NS1619 + Ca(2+)-reduction 1.17 +/- 0.06; NS1619 + PD98059 1.06 +/- 0.49; NS1619 + U0126 1.10 +/- 0.24; n=10; p<0.05). The phosphorylation of eNOS and p42/p44(MAPK) was examined by immunocytochemistry. Phosphorylation of p42/p44(MAPK) was significantly increased after 10 minutes of NS1619 stimulation, whereas eNOS phosphorylation was not changed over a period of 1 to 30 minutes. NS1619-induced hyperpolarization was not affected by treatment with PD 98059 or U0126. Additionally, NS1619 inhibited endothelial proliferation involving a NO-dependent mechanism. Our data demonstrate that NS1619 causes a transmembrane Ca(2+)-influx leading to an increased NO production involving p42/p44(MAPK). This rise of NO formation is responsible for the NS1619 induced reduction of endothelial cell growth.

Dose-dependent activation of Ca2+-activated K+ channels by ethanol contributes to improved endothelial cell functions.

BACKGROUND: Regular moderate alcohol (EtOH) intake seems to protect against both coronary artery disease and ischemic stroke, whereas the risk increases with heavy EtOH consumption. Effects of EtOH on endothelial cell function may be relevant to these disparate effects. Potassium channels play an important role in the regulation of endothelial cell functions. Therefore, we investigated whether Ca-activated K channels (BKCa) are modulated by EtOH. Furthermore, we examined whether EtOH-induced changes of endothelial nitric oxide (NO) formation and cell proliferation are due to BKCa activation. METHODS: The patch-clamp technique was used to investigate BKCa activity in cultured human umbilical vein endothelial cells (HUVEC). NO formation was analyzed by using the fluorescence dye 4,5-diaminofluorescein. Endothelial proliferation was examined by using cell counts and measuring [H]thymidine incorporation. RESULTS: EtOH dose-dependently (10-150 mmol/liter) modulated BKCa-activity, with the highest increase of open-state probability at a concentration of 50 mmol/liter (n = 13; p < 0.05). Inside-out recordings revealed that this effect was due to direct BKCa activation, whereas open-state probability was not changed in cell-attached recordings after pertussis toxin preincubation. EtOH (10 and 50 mmol/liter) caused a significant increase of NO levels, which was blocked by the highly selective BKCa inhibitor iberiotoxin (100 nmol/l; n = 30; p < 0.05). Higher concentrations of EtOH (100 and 150 mmol/liter) significantly reduced NO synthesis (n = 30; p < 0.05). Both methods revealed a significant increase of HUVEC proliferation, which was inhibited by iberiotoxin (n = 30; p < 0.05). At a concentration of 150 mmol/liter, EtOH caused a significant reduction of endothelial proliferation. CONCLUSIONS: EtOH directly activates BKCa in HUVEC, leading to an increase of endothelial proliferation and production of NO. These results indicate a possible beneficial effect of low-dose EtOH on endothelial function, whereas higher concentrations must be considered as harmful.

Lysophosphatidylcholine-induced modulation of Ca(2+)-activated K(+)channels contributes to ROS-dependent proliferation of cultured human endothelial cells.

Proliferation of endothelial cells plays a crucial role in the process of atherosclerotic plaque destabilization. The major component of oxidized low-density lipoprotein lysophosphatidylcholine (LPC) has been shown to promote endothelial proliferation by increasing the production of reactive oxygen species (ROS). Since K(+) channels are known to control the cell cycle, we investigated the role of Ca(2+)-activated K(+) channels (BK(Ca)) in the regulation of LPC-induced endothelial proliferation and ROS generation. A significant increase of cell growth induced by LPC (20 micromol/l; cell counts (CCs): +87%, thymidin incorporation: +89%; n = 12, P < 0.01) was observed, which was inhibited by the BK(Ca) inhibitor iberiotoxin (IBX; 100 nmol/l), by the NAD(P)H-oxidase inhibitor diphenyleneiodonium (5 micromol/l) and by transfection with antisense (AS) oligonucleotides against NAD(P)H oxidase, whereas N(G)-monomethyl-l-arginine (l-NMMA) further increased LPC-induced cell growth. Using the patch-clamp technique a significant increase of BK(Ca) open-state probability (control: 0.004 +/- 0.002; LPC: 0.104 +/- 0.035; n = 21, P < 0.05) by LPC was observed. Using dichlorofluorescein fluorescence microscopy a significant increase of ROS induced by LPC was reported, that was blocked by IBX and Ca(2+) antagonists. Intracellular Ca(2+) measurements revealed a capacitative Ca(2+) influx caused by LPC. Bioactivity of nitric oxide (NO) was measured using a [(3)H]-cGMP radioimmunoassay. LPC significantly decreased acetylcholine-induced NO synthesis. LPC significantly increased cGMP levels in endothelial cells transfected with AS, which was blocked by IBX. In conclusion, our results demonstrate that LPC activates BK(Ca) thereby increasing ROS production which induces endothelial proliferation. In addition LPC-induced BK(Ca)-activation contributes to increased cGMP levels, if ROS production is prevented by AS.