Maternal Streptococcus agalactiae colonization in Europe: data from the multi-center DEVANI study.

INTRODUCTION: Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD). METHODS: Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study. Clinical obstetrical information was collected by a standardized questionnaire. GBS strains were characterized by serological and molecular methods. RESULTS: Among GBS carriers included in this study after testing positive for GBS by vaginal or recto-vaginal sampling, 13.4% had at least one additional obstetrical risk factor for EOD. The five most common capsular types (i.e., Ia, Ib, II, III and V) comprised ~ 93% of GBS carried. Of the colonized women, 77.8% received any IAP, and in 49.5% the IAP was considered appropriate. In our cohort, nine neonates presented with GBS early-onset disease (EOD) with significant regional heterogeneity. CONCLUSIONS: Screening methods and IAP rates need to be harmonized across Europe in order to reduce the rates of EOD. The epidemiological data from eight different European countries provides important information for the development of a successful GBS vaccine.

Does structured obstetric management play a role in the delivery mode and neonatal outcome of twin pregnancies?

PURPOSE: While the optimal delivery method of twin pregnancies is debated, the rate of cesarean deliveries is increasing. This retrospective study evaluates delivery methods and neonatal outcome of twin pregnancies during two time periods and aims to identify predictive factors for the delivery outcome. METHODS: 553 twin pregnancies were identified in the institutional database of the University Women's Hospital Freiburg, Germany. 230 and 323 deliveries occurred in period I (2009-2014) and period II (2015-2021), respectively. Cesarean births due to non-vertex position of the first fetus were excluded. In period II, the management of twin pregnancies was reviewed; adjusted and systematic training with standardized procedures was implemented. RESULTS: Period II showed significantly lower rates of planned cesarean deliveries (44.0% vs. 63.5%, p < 0.0001) and higher rates of vaginal deliveries (68% vs. 52.4%, p = 0.02). Independent risk factors for primary cesarean delivery were period I, maternal age > 40 years, nulliparity, a history with a previous cesarean, gestational age < 37 completed weeks, monochorionicity and increasing birth weight difference (per 100 g or > 20%). Predictive factors for successful vaginal delivery were previous vaginal delivery gestational age between 34 and 36 weeks and vertex/vertex presentation of the fetuses. The neonatal outcomes of period I and II were not significantly different, but planned cesareans in general were associated with increased admission rates to the neonatal intensive care units. Inter-twin interval had no significant impact on neonatal outcome. CONCLUSION: Structured regular training of obstetrical procedures may significantly reduce high cesarean rates and increase the benefit-risk ratio of vaginal deliveries.

[Evaluation of Psychological Distress in Obstetric Patients during the Visit Ban in Hospitals in the SARS-CoV-2 Pandemic: A Prospective, Multicentre, Controlled Study]. / Evaluation der psychischen Belastung geburtshilflicher Patientinnen während des Besuchsverbots der Kliniken im Rahmen der SARS-CoV-2-Pandemie: Eine prospektive, multizentrische, kontrollierte Studie.

INTRODUCTION: Risk factors for postpartum depression include a lack of social support and perceived social isolation. We would like to determine whether the isolation of inpatients on the maternity wards during Covid-19 leads to increased psychological stress. METHODS: This is a multicentre, controlled study of obstetric patients who gave birth during an inpatient stay. Patients were included during the visitation ban (study group) and after the visitation ban (control group). Psychological stress was evaluated with the Edinburgh Postnatal Depression Scale (EPDS) during the inpatient stay and six to eight weeks postpartum. RESULTS: A total of 194 women were included, 107 in the study group and 87 in the control group. The overall result of the first EPDS shows a higher score in the study group compared to the control group (7.0 vs. 4.9 points). Primipara show a higher score in the first EPDS compared to multipara (7.28 vs. 4.82). Caesarean section, regardless of isolation, shows a higher score in the first EPDS than vaginal birth (8.42 vs. 5.11). Comparison of vaginal birth shows a higher score only in the study group (5.97 vs. 4.07). CONCLUSION: In the context of Covid-19, women giving birth and new mothers, especially primipara, are exposed to increased psychological stress in the clinics. Caesarean section leads to increased psychological stress.

Evolution of Fetal Growth in Symptomatic Sars-Cov-2 Pregnancies.

INTRODUCTION: SARS-CoV-2 is a viral disease with potentially devastating effects. Observational studies of pregnant women infected with SARS-CoV-2 report an increased risk for FGR. This study utilizes data from a prospective SARS-CoV-2 registry in pregnancy, investigating the progression of fetuses to fetal growth restriction (FGR) at birth following maternal SARS-CoV-2 and evaluating the hypothesis of whether the percentage of SGA at birth is increased after maternal SARS-CoV-2 taking into account the time interval between infection and birth. MATERIALS & METHODS: CRONOS is a prospective German registry enrolling pregnant women with confirmed SARS-CoV-2 infection during their pregnancy. SARS-CoV-2 symptoms, pregnancy- and delivery-specific information were recorded. The data evaluated in this study range from March 2020 until August 2021. Women with SARS-CoV-2 were divided into three groups according to the time of infection/symptoms to delivery: Group I<2 weeks, Group II 2-4 weeks, and Group III>4 weeks. FGR was defined as estimated and/or birth weight<10% ile, appropriate for gestational age (AGA) was within 10 and 90%ile, and large for gestational age (LGA) was defined as fetal or neonatal weight>90%ile. RESULTS: Data for a total of 2,650 SARS-CoV-2-positive pregnant women were available. The analysis was restricted to symptomatic cases that delivered after 24+0 weeks of gestation. Excluding those cases with missing values for estimated fetal weight at time of infection and/or birth weight centile, 900 datasets remained for analyses. Group I consisted of 551 women, Group II of 112 women, and Group III of 237 women. The percentage of changes from AGA to FGR did not differ between groups. However, there was a significantly higher rate of large for gestational age (LGA) newborns at the time of birth compared to the time of SARS-CoV-2 infection in Group III (p=0.0024), respectively. CONCLUSION: FGR rates did not differ between symptomatic COVID infections occurring within 2 weeks and>4 weeks before birth. On the contrary, it presented a significant increase in LGA pregnancies in Group III. However, in this study population, an increase in the percentage of LGA may be attributed to pandemic measures and a reduction in daily activity.

Placenta Accreta Spectrum (PAS): Diagnosis, Clinical Presentation, Therapeutic Approaches, and Clinical Outcomes.

Placenta accreta spectrum (PAS) refers to the abnormal adhesion of the placenta to the myometrium, with varying degrees of severity. Placenta accreta involves adhesion to the myometrium, placenta increta invades the myometrium, and placenta percreta extends through the serosa to adjacent organs. The condition is linked to deficient decidualization in scarred uterine tissue, and the risk increases when placenta previa is present and with each prior cesarean delivery. Other risk factors include advanced maternal age, IVF, short intervals between cesareans, and smoking. PAS incidence has risen due to the increase in cesarean deliveries. Placenta previa combined with PAS significantly raises the risk of severe peripartum bleeding, often necessitating a cesarean section with a total hysterectomy. Recognizing PAS prepartum is essential, with sonographic indicators including intraplacental lacunae and uterovesical hypervascularization. However, PAS can be present without sonographic signs, making clinical risk factors crucial for diagnosis. Effective management requires a multidisciplinary approach and proper infrastructure. This presentation covers PAS cases treated at University Hospital Freiburg, detailing patient conditions, diagnostic methods, treatments and outcomes.

Neonatal invasive disease caused by Streptococcus agalactiae in Europe: the DEVANI multi-center study.

PURPOSE: Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis and meningitis, in infants < 3 months of age and of mortality among neonates. This study, a major component of the European DEVANI project (Design of a Vaccine Against Neonatal Infections) describes clinical and important microbiological characteristics of neonatal GBS diseases. It quantifies the rate of antenatal screening and intrapartum antibiotic prophylaxis among cases and identifies risk factors associated with an adverse outcome. METHODS: Clinical and microbiological data from 153 invasive neonatal cases (82 early-onset [EOD], 71 late-onset disease [LOD] cases) were collected in eight European countries from mid-2008 to end-2010. RESULTS: Respiratory distress was the most frequent clinical sign at onset of EOD, while meningitis is found in > 30% of LOD. The study revealed that 59% of mothers of EOD cases had not received antenatal screening, whilst GBS was detected in 48.5% of screened cases. Meningitis was associated with an adverse outcome in LOD cases, while prematurity and the presence of cardiocirculatory symptoms were associated with an adverse outcome in EOD cases. Capsular-polysaccharide type III was the most frequent in both EOD and LOD cases with regional differences in the clonal complex distribution. CONCLUSIONS: Standardizing recommendations related to neonatal GBS disease and increasing compliance might improve clinical care and the prevention of GBS EOD. But even full adherence to antenatal screening would miss a relevant number of EOD cases, thus, the most promising prophylactic approach against GBS EOD and LOD would be a vaccine for maternal immunization.

Emergency button cannula vs. umbilical catheter as neonatal emergency umbilical vein access - a randomized cross-over pilot study.

OBJECTIVES: Establishing immediate intravenous access to a newborn is challenging even for trained neonatologists in an emergency situation. Correct placement of umbilical catheter or an intraosseous needle needs consistent training. We evaluated the time required to correctly place an emergency umbilical button cannula (EUC) or an umbilical catheter (UC) using the standard intersection (S-EUC or S-UC, respectively) or lateral umbilical cord incision (L-EUC) by untrained medical personnel. METHODS: Single-center cross-over pilot-study using a model with fresh umbilical cords. Video-based teaching of medical students before probands performed all three techniques after assignment to one of three cycles with different sequence, using a single umbilical cord divided in three pieces for each proband. RESULTS: Mean time required to establish L-EUC was 89.3 s, for S-EUC 82.2 s and for S-UC 115.1 s. Both application routes using the EUC were significantly faster than the UC technique. There was no significant difference between both application routes using EUC (p=0.54). CONCLUSIONS: Using an umbilical cannula is faster than an umbilical catheter, using a lateral incision of the umbilical vein is an appropriate alternative.

Postnatal genetic umbilical cord analysis for earliest possible detection of inherited hearing impairment.

INTRODUCTION: The most common sensorineural disorder in humans is hearing impairment and approximately 60% of prelingual hearing disorders are genetic. Especially parents with a congenital deaf child want to know as early as possible whether their second born child has the same genetic defect or not. The aim of this study is to demonstrate that postnatal genetic umbilical cord analysis is both the earliest detection possibility and sufficient. METHODS: We included first born children with severe hearing impairment that underwent cochlear implantation. All included patients were analyzed genetically and exhibited mutations of either DFNB1 loci or SLC26A4 gene. Additionally, the umbilical cord of the sibling underwent genetic analysis to detect hereditary genetic mutations as early as possible. RESULTS: 49 newborn children out of 22 families were included in this study. Genetic analysis revealed clinical relevant mutations in all first born children and in four siblings via umbilical cord analysis. All patients who have been diagnosed with a relevant genetic mutation that caused severe hearing impairment underwent hearing rehabilitation via cochlear implant surgery. CONCLUSION: This study demonstrates the sufficient and early as possible detection of known genetically hearing disorders via umbilical cord analysis. In case of a known familial genetic hearing disorder, it is advisable to analyze newborn siblings for the corresponding genetic defect as soon as possible, to be able to plan and initiate clinical care for the patient as early as possible. It is also extremely important for the parents to obtain clear information about the auditory status of the newborn.

Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking. OBJECTIVE: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19. STUDY DESIGN: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19-associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints. RESULTS: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88-2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43-5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38-6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m2 increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05-3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26-2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32-2.48) primary endpoints compared with underweight or normal weight. CONCLUSION: Gestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m2 were a particularly vulnerable group in the case of COVID-19.

[Individualized Somatic Classification of Newborns Using Birth Weight Percentiles Based On Maternal Body Height and Weight (Results of a Validation Study)]. / Individuelle somatische Klassifikation von Neugeborenen auf der Grundlage von Körperhöhe und Körpergewicht der Mutter (Ergebnisse einer Validierungsstudie).

INTRODUCTION: Birth weight is influenced by maternal anthropometry. The SGA-rate of newborns of short and light mothers (<158 cm,<53 kg) and the LGA-rate of tall and heavy mothers (>177 cm,>79 kg) are overestimated. The LGA-rate of newborns of shorter mothers and the SGA-rate of taller mothers are underestimated. Individualized birth weight percentiles (IBWP) based on 18 maternal groups (6 groups of height combined with 3 groups of weight), sex and weeks of gestation have been published. The aim of this study is to validate IBWP by evaluating SGA-, AGA-, and LGA-rates using perinatal data. METHODS: The validation study compares IBWP (1995 to 2000, n=2.2 million singletons) with percentile values from two German cohorts (i: 1995 to 2000; n=2.3 million and ii: 2007 to 2011, n=3.2 million singletons) using newborns from the Lower Saxony Perinatal Survey (n=0.56 million singleton newborns, 2001 to 2009). SGA-, AGA-, and LGA-rates were calculated using R statistical analysis. RESULTS: Common percentile charts based on the total population 1995-2000 and 2007-2011 yielded SGA-rates among shorter mothers of 21.1 to 21.6% and LGA-rates of 2.0 to 3.1%. In taller mothers, SGA-rates were 3.3 to 3.5% and LGA-rates were 26.6 to 27.1%. IBWP achieved SGA-rates of 9.0% and LGA-rates of 11.4 to 11.6% in shorter mothers and SGA- and LGA-rates of 10% in taller mothers. DISCUSSION: IBWP consider the maternal size for estimation of the fetal growth potential and achieve expected SGA- and LGA-rates of 10%. Consideration of individual growth potential avoids underestimation and overestimation of SGA- and LGA-rates. It aided analyses of birth weight with IBWP simplify the assessment of the nutritional status.

Inhibition of the anti-apoptotic protein MCL-1 severely suppresses human hematopoiesis

BH3-mimetics inhibiting anti-apoptotic BCL-2 proteins represent a novel and promising class of antitumor drugs. While the BCL-2 inhibitor venetoclax is already FDA-approved, BCL-XL and MCL-1 inhibitors are currently in early clinical trials. To predict side effects of therapeutic MCL-1 inhibition on the human hematopoietic system, we used RNAi and the small molecule inhibitor S63845 on cord blood-derived CD34+ cells. Both approaches resulted in almost complete depletion of human hematopoietic stem and progenitor cells. As a consequence, maturation into the different hematopoietic lineages was severely restricted and CD34+ cells expressing MCL-1 shRNA showed a very limited engraftment potential upon xenotransplantation. In contrast, mature blood cells survived normally in the absence of MCL-1. Combined inhibition of MCL-1 and BCL-XL resulted in synergistic effects with relevant loss of colony-forming HSPCs already at inhibitor concentrations of 0.1 µM each, indicating "synthetic lethality" of the two BH3-mimetics in the hematopoietic system.

[The Neonatal Subgaleal Hematoma - A Neonatal Emergency]. / Das subgaleale Hämatom beim Neugeborenen ­ ein neonatologischer Notfall.

Subgaleal hematoma (SGH) is a rare complication in neonates that may lead to hemorrhagic shock due to significant blood loss into the subgaleal space. We report of two neonates who developed subgaleal hematoma with severe hemorrhagic shock and encephalopathy. In the first case of a mature female neonate, the development of the subgaleal hematoma was promoted by early-onset sepsis and delivery by vacuum extraction. The second case, of a male preterm neonate, was a complicated fetal development followed by secondary cesarean section. Both cases highlight that a subgaleal hematoma is a severe neonatal emergency. In addition to prompt treatment of the shock, therapy of the coagulopathy is essential.

[Current approach in preterm prelabor rupture of membranes: new definitions? Is CRP determination useful? Are alternatives in sight?] / Aktuelles Vorgehen bei frühem vorzeitigem Blasensprung: neue Definitionen? Ist die CRP-Bestimmung sinnvoll? Sind Alternativen in Sicht?

Around 3% of all pregnancies are complicated by preterm prelabor rupture of membranes (PPROM) before 37 + 0 weeks of gestation. Since PPROM is likely to be associated with microbial invasion of the amniotic cavity (MIAC)-either before or secondary to PPROM-the risk of developing intraamniotic inflammation (IAI) is high. IAI is associated with short latency to delivery and with adverse short- and long-term outcomes for the newborn, especially in cases of fetal inflammatory response syndrome (FIRS). Prediction of IAI based on maternal parameters is difficult or impossible. The recently established definition of triple I ("infection, inflammation, or both") is based on the parameter "maternal body temperature". If this is increased to ≥ 38.0 °C and there is no other reason to explain maternal fever, the finding is suspicious for triple I if at least one other of the following parameters can be found: fetal tachycardia > 160 bpm for at least 10 min, maternal leukocytes > 15,000/µl without administration of corticosteroids, or purulent fluid from the cervical os. Pregnancies suspicious for triple I should be terminated. The confirmation of triple I is only possible by placental histology (histologically confirmed chorioamnionitis, HCA). Confirmation based on amniocentesis (positive Gram stain, low glucose concentration [<14 mg/dl], elevated white blood cell count [>30 cells/mm3], positive culture) takes too long and is unreliable. Serial determinations of C­reactive protein also do not allow reliable diagnosis of IAI. Studies using interleukin 6 measurements from the posterior fornix and/or cervical os are promising methods, the validation of which is awaited.

Individualized birth length and head circumference percentile charts based on maternal body weight and height.

Objectives Measurement of birth length and birth head circumference is part of the newborn assessment. Both measurements aid in distinguishing between proportionate and disproportionate small and large for gestational age newborns. It had been shown that birth weight is related to maternal height and weight. This study aims to analyze birth length and birth head circumference percentiles based on maternal stature. Methods This observational study analyzed birth length and birth head circumference percentiles of 2.3 million newborns stratified by maternal height and weight from the first obstetric assessment. Percentiles were calculated for sex and 22-43 gestational weeks for all infants. Eighteen subgroups based on six maternal height and three weight strata were defined and percentiles calculated from 32 to 42 gestational weeks using GAMLSS package for R. Results Newborns of mothers with height <158 cm and weight <53 kg (short stature) had a rate of preterm birth of 9%, compared to 5% in the tall stature group (height >177 cm, weight >79 kg). Small stature mothers were 1.7 years younger. Birth length differed by several centimeters for the same percentiles between groups of short and tall stature mothers, whereas birth head circumference differed up to 1.2 cm. The largest deviation of birth length was between the 97th percentiles. For male newborns born at term, birth length at the 97th percentile differed by 3.2 cm, at the 50th percentile by 2.7 cm and at the third percentile by 2.5 cm. Conclusions Birth length and birth head circumference are related to maternal height and weight. To more completely assess newborns, the maternal size should be considered.

Individualized sex-specific birth weight percentiles for gestational age based on maternal height and weight.

OBJECTIVES: The maternal body size affects birth weight. The impact on birth weight percentiles is unknown. The objective of the study was to develop birth weight percentiles based on maternal height and weight. METHODS: This observational study analyzed 2.2 million singletons from the German Perinatal Survey. Data were stratified into 18 maternal height and weight groups. Sex-specific birth weight percentiles were calculated from 31 to 42 weeks and compared to percentiles from the complete dataset using the GAMLSS package for R statistics. RESULTS: Birth weight percentiles not considering maternal size showed 22% incidence of small for gestational age (SGA) and 2% incidence of large for gestational age (LGA) for the subgroup of newborns from petite mothers, compared to a 4% SGA and 26% LGA newborns from big mothers. The novel percentiles based on 18 groups stratified by maternal height and weight for both sexes showed significant differences between identical original percentiles. The differences were up to almost 800 g between identical percentiles for petite and big mothers. The 97th and 50th percentile from the group of petite mothers almost overlap with the 50th and 3rd percentile from the group of big mothers. CONCLUSIONS: There is a clinically significant difference in birth weight percentiles when stratified by maternal height and weight. It could be hypothesized that birth weight charts stratified by maternal anthropometry could provide higher specificity and more individual prediction of perinatal risks. The new percentiles may be used to evaluate estimated fetal as well as birth weight.

In vitro and in vivo evaluation of possible pro-survival activities of PGE2, EGF, TPO and FLT3L on human hematopoiesis.

Myelosuppression is a major and frequently dose-limiting side effect of anticancer therapy and is responsible for most treatment-related morbidity and mortality. In addition, repeated cycles of DNA damage and cell death of hematopoietic stem and progenitor cells, followed by compensatory proliferation and selection pressure, lead to genomic instability and pave the way for therapy-related myelodysplastic syndromes and secondary acute myeloid leukemia. Protection of hematopoietic stem and progenitor cells from chemo- and radiotherapy in patients with solid tumors would reduce both immediate complications and long-term sequelae. Epidermal growth factor (EGF) and prostaglandin E2 (PGE2) were reported to prevent chemo- or radiotherapy-induced myelosuppression in mice. We tested both molecules for potentially protective effects on human CD34+ cells in vitro and established a xenograft mouse model to analyze stress resistance and regeneration of human hematopoiesis in vivo EGF was neither able to protect human stem and progenitor cells in vitro nor to promote hematopoietic regeneration following sublethal irradiation in vivo PGE2 significantly reduced in vitro apoptotic susceptibility of human CD34+ cells to taxol and etoposide. This could, however, be ascribed to reduced proliferation rather than to a change in apoptosis signaling and BCL-2 protein regulation. Accordingly, 16,16-dimethyl-PGE2 (dmPGE2) did not accelerate regeneration of the human hematopoietic system in vivo Repeated treatment of sublethally irradiated xenograft mice with known antiapoptotic substances, such as human FLT3L and thrombopoietin (TPO), which suppress transcription of the proapoptotic BCL-2 proteins BIM and BMF, also only marginally promoted human hematopoietic regeneration in vivo.

The role of tongue-tie in breastfeeding problems-A prospective observational study.

AIM: We evaluated what determined breastfeeding problems in a non-selected mother-infant cohort, with special reference to tongue-tie and improvements in breastfeeding following frenulotomy. METHODS: This 2014-2015 prospective, observational study was carried out in a tertiary level maternity unit affiliated to the University of Freiburg, Germany, using a breastfeeding questionnaire, standardised breastfeeding scores and the Assessment Tool For Lingual Frenulum Function (ATLFF). The standard intervention was breastfeeding support, a frenulotomy for tongue-tie was performed if necessary. All cases of breastfeeding problems and, or tongue-tie, were followed up by telephone 2.5 weeks after birth. RESULTS: We enrolled 776 newborn-mother dyads: 345 had breastfeeding problems, 116 had a tongue-tie and 30 underwent a frenulotomy. In the multivariate analysis, severe breastfeeding problems were more frequent in newborn infants with tongue-tie, with an odds ratio (OR) of 2.6 (P= 0.014). Other risk factors were: no breastfeeding experience (OR 4.4, P = 0.001), low birth weight (OR 2.9, P = 0.001), prematurity (OR 3.6, P = 0.000) and Caesarean section (OR 1.6, P = 0.023). There was a significant reduction in breastfeeding problems after frenulotomy (P = 0.01). CONCLUSION: Tongue-tie had a significant impact on breastfeeding and so did low birth weights and prematurity. Frenulotomy proved helpful when breastfeeding problems were reported.

Lipoprotein turnover and possible remnant accumulation in preeclampsia: insights from the Freiburg Preeclampsia H.E.L.P.-apheresis study.

BACKGROUND: Preeclampsia is a life-threatening disease in pregnancy, and its complex pathomechanisms are poorly understood. In preeclampsia, lipid metabolism is substantially altered. In late onset preeclampsia, remnant removal disease like lipoprotein profiles have been observed. Lipid apheresis is currently being explored as a possible therapeutic approach to prolong preeclamptic pregnancies. Here, apheresis-induced changes in serum lipid parameters are analyzed in detail and their implications for preeclamptic lipid metabolism are discussed. METHODS: In the Freiburg H.E.L.P.-Apheresis Study, 6 early onset preeclamptic patients underwent repeated apheresis treatments. Serum lipids pre- and post-apheresis and during lipid rebound were analyzed in depth via ultracentrifugation to yield lipoprotein subclasses. RESULTS: The net elimination of Apolipoprotein B and plasma lipids was lower than theoretically expected. Lipids returned to previous pre-apheresis levels before the next apheresis even though apheresis was repeated within 2.9 ± 1.2 days. Apparent fractional catabolic rates and synthetic rates were substantially elevated, with fractional catabolic rates for Apolipoprotein B / LDL-cholesterol being 0.7 ± 0.3 / 0.4 ± 0.2 [day- 1] and synthetic rates being 26 ± 8 / 17 ± 8 [mg*kg- 1*day- 1]. The distribution of LDL-subclasses after apheresis shifted to larger buoyant LDL, while intermediate-density lipoprotein-levels remained unaffected, supporting the notion of an underlying remnant removal disorder in preeclampsia. CONCLUSION: Lipid metabolism seems to be highly accelerated in preeclampsia, likely outbalancing remnant removal mechanisms. Since cholesterol-rich lipoprotein remnants are able to accumulate in the vessel wall, remnant lipoproteins may contribute to the severe endothelial dysfunction observed in preeclampsia. TRIAL REGISTRATION: ClinicalTrails.gov, NCT01967355 .

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients. Part II: Therapy and Prevention.

BACKGROUND: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. MATERIALS AND METHODS: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010-2015. RESULTS: For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. CONCLUSION: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.