[Single dose of misoprostol for abortion until 9 weeks of gestation]. / Efficacité d'une dose unique de misoprostol pour les interruptions volontaires de grossesse jusqu'à 9 semaines d'aménorrhée.

OBJECTIVES: The primary objective was to compare the efficacy of a single-dose misoprostol for abortion before 7 weeks of gestation and between 7 and 9 weeks of gestation. The secondary objectives were to compare the amount of misoprostol required for complete expulsion, the need for endo-uterine aspiration, and to assess pain and patient experience in these two groups. METHODS: This was a single-centre prospective observational study conducted at the University Hospitals of Strasbourg from 1st October 2019 to 31st December 2020. RESULTS: A total of 306 patients were included, 150 in the group before 7 weeks of gestation and 156 in the group between 7 and 9 weeks of gestation. There was no significant difference in the success rate of the single dose of misoprostol between the two groups with 34.7 and 37.8% respectively (P=0.63). After taking painkillers, there is no difference in terms of pain relief (EN ≤ 4 for 92 et 95% of patients P=0.37). CONCLUSION: The single dose of misoprostol for in-hospital abortion is as effective between 7 and 9 weeks of gestation as it is before 7. By extension, therefore, we would suggest that there should be no difference in efficacy between home abortions before 7 weeks of gestation and between 7 and 9 weeks of gestation and therefore suggest that home abortions can be performed up to 9 weeks of gestation without fear of a decrease in the rate of complete expulsion and the efficacy of analgesia, with potentially less use of misoprostol compared with the hospital setting.

[Temporary urethral stents changes as an alternative treatment for neurological bladder]. / Les changements itératifs de prothèse urétrale trans-sphinctérienne chez le patient neurologique : une alternative à la sphinctérotomie ?

BACKGROUND: Patients with detrusor-sphincter dysynergia (DSD) who are unable to perform self-catheterisation can benefit from an endoscopic treatment. We chose regular urethral stent changes as an alternative to sphincterotomy in this kind of patients. The purpose of this study is to show that temporary urethral stents changes represent a treatment option with a reasonable morbidity for patients with DSD. METHODS: We retrospectively reviewed patients in our center who had been treated with urethral stents from April 2005 to September 2017. The stent changes were performed every 12 to 18 months depending on urethrovesical fibroscopy findings. The primary endpoint was treatment continuation. RESULTS: A total of 44 patients were enrolled in our study and the average follow-up duration was 46 months [18.5-53.25]. Primary treatment failure was seen in 14 (32%) patients mainly due to problems related to equipment (n=3) and urinary retention (n=2). Four patients died before their first stent change. The treatment was successful in 30 (68%) patients, of whom 10 (33%) subsequently adopted a voiding mode change. We lost sight of 5 patients (11%) during follow-up. The main complications were urinary retention (29%), urinary tract infections (27%) and stent migration (18%). Fifteen (34%) experienced grade III-IV complications. CONCLUSIONS: Regular urethral stent changes represent an alternative treatment option for patients with DSD but with a significant morbidity. LEVEL OF EVIDENCE: 4.

Taking the next step forward - Diagnosing inherited infantile cholestatic disorders with next generation sequencing.

Identifying rare genetic forms of infantile cholestasis is challenging due to their similar clinical presentation and their diverse etiology. After exclusion of common non-genetic causes a huge list of rare differential diagnosis remains to be solved. More than 90 genes are associated with monogenic forms of infantile cholestasis, thus preventing routine genetic workup by Sanger sequencing. Here we demonstrate a next generation sequencing approach to discover the underlying cause in clinically well characterized patients in whom common causes of infantile cholestasis have been excluded. After validation of the analytical sensitivity massive parallel sequencing was performed for 93 genes in six prospectively studied patients. Six novel mutations (PKHD1: p.Thr777Met, p.Tyr2260Cys; ABCB11: p.Val1112Phe, c.611+1G > A, p.Gly628Trpfs*3 and NPC1: p.Glu391Lys) and two known pathogenic mutations were detected proving our multi gene panel for infantile cholestasis to be a sensitive and specific method overcoming the complexity of the phenotype-based, candidate gene approach. Three exemplary clinical cases of infants with cholestasis are presented and discussed in the context of their genetic and histopathological findings (autosomal recessive polycystic kidney disease, atypical PFIC and Niemann-Pick syndrome type C1). These case reports highlight the critical impact of integrating clinical, histopathological and genetic data during the process of multi gene panel testing to ultimately pinpoint rare genetic diagnoses.

S3-Guidelines for the Treatment of Inflammatory Breast Disease during the Lactation Period: AWMF Guidelines, Registry No. 015/071 (short version) AWMF Leitlinien-Register Nr. 015/071 (Kurzfassung).

Breastfeeding is widely acknowledged to be the best and most complete form of nutrition for healthy infants born at term and is associated with numerous benefits in terms of infants' health, growth, immunity and development. However, breastfeeding problems often result in early weaning. Standardized treatment recommendations for breastfeeding-related diseases are necessary to optimize the care offered to breastfeeding women. Evidence and consensus based guidelines for the treatment of puerperal mastitis, sore nipples, engorgement and blocked ducts were developed on the initiative of the National Breastfeeding Committee. These guidelines were developed in accordance with the criteria set up by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF), the Association of Scientific Medical Societies in Germany. The recommendations were drawn up by an interdisciplinary group of experts and were based on a systematic search and evaluation of the literature but also took clinical experience into account. Additionally good clinical practice (GCP) in terms of expert opinion was formulated in cases where scientific investigations could not be performed or were not aimed for. This article presents a summary of the recommendations of the S3-guidelines.

Somatostatin - therapeutic option for chylothorax in preterm neonates. Report on two patients and review of the literature.

We report the use of somatostatin in two preterm neonates with chylothorax and discuss those cases in the light of current literature on the treatment of chylothorax in infants born preterm. Chylothorax, a severe complication in thorax surgery, is also a symptom of different diseases and may even occur spontaneously. Treatment is difficult, especially in preterm neonates with co-morbidities. The standard therapeutic strategy with non-invasive procedures (e.g. enteral diet free of long chain triglycerides or parenteral nutrition) is not always effective. Surgical interventions, like pleurodesis, ligation of the ductus thoracicus, or pleuroperitoneal shunt may be of considerable risk in preterm infants and must be carefully evaluated. Somatostatin is a new non-invasive therapeutic option for the treatment of chylothorax in adults and older pediatric patients. Case reports demonstrate the effectiveness of the somatostatin treatment, mostly in adult patients and in adolescents. There are only few case reports describing the use of somatostatin in preterm neonates. One VLBW (very low birth weight) and one hypotrophic ELBW (extremely low birth weight) neonate (gestational ages of 30+3/7, and 25+2/7 weeks; birth weights of 1270g, and 450g respectively) were treated for chylothorax with continuous infusion of somatostatin in addition to the dietary treatment. The chylothorax disappeared after start of somatostatin. No major side-effects of the somatostatin treatment were observed. As reported in other published pediatric cases, somatostatin seems to be a therapeutic option for the treatment of chylothorax in preterm neonates. In review of the literature we identified another eleven case reports on the treatment of persistent chylothorax with somatostatin or octreotide in preterm neonates. Further observations are needed before somatostatin can be recommended as a standard first-line treatment procedure for chylothorax in infants.

Neonatology/Paediatrics - Guidelines on Parenteral Nutrition, Chapter 13.

There are special challenges in implementing parenteral nutrition (PN) in paediatric patients, which arises from the wide range of patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg, and their varying substrate requirements. Age and maturity-related changes of the metabolism and fluid and nutrient requirements must be taken into consideration along with the clinical situation during which PN is applied. The indication, the procedure as well as the intake of fluid and substrates are very different to that known in PN-practice in adult patients, e.g. the fluid, nutrient and energy needs of premature infants and newborns per kg body weight are markedly higher than of older paediatric and adult patients. Premature infants <35 weeks of pregnancy and most sick term infants usually require full or partial PN. In neonates the actual amount of PN administered must be calculated (not estimated). Enteral nutrition should be gradually introduced and should replace PN as quickly as possible in order to minimise any side-effects from exposure to PN. Inadequate substrate intake in early infancy can cause long-term detrimental effects in terms of metabolic programming of the risk of illness in later life. If energy and nutrient demands in children and adolescents cannot be met through enteral nutrition, partial or total PN should be considered within 7 days or less depending on the nutritional state and clinical conditions.

Quality of care of VLBW neonates: relationship between unit volume and outcome is different between metropolitan and rural regions.

BACKGROUND: Recent studies from predominantly rural areas in Germany show that neonatal outcome of very low birth weight (VLBW) neonates is (on average) inferior with lower NICU (neonatal intensive care unit) volume. However, there are no data available which show that study results of one specific region can be transferred to other areas with possibly different medical infrastructure and needs. AIM: It was investigated whether a systematic difference of treatment quality between smaller (1000-2000 births/year; < or =20 neonatal beds) vs. larger neonatal centres in Berlin (>3000 births/year; >20 neonatal beds) exists. Furthermore, the results are compared to data from a rural region in order to discuss transferability between regions. METHODS: Retrospectively, completely, and for the first time, the data of all centres which treat VLBW neonates (< or =1500 g birth weight) in the city-state of Berlin, Germany, from the years 2003/2004 were reviewed. RESULTS: Our study showed no difference in the treatment quality of smaller vs. larger neonatal units in Berlin. This result differs from those of a study in Baden-Württemberg, a predominantly rural state, with different medical infrastructure than Berlin. CONCLUSION: The present study suggests that regional investigations on the infrastructure vs. treatment outcome are not transferable between areas. Patient volume/unit appears inadequate for predicting the future treatment quality of neonatal departments. Direct quality indicators are stable for the assessed departments and should be preferably used to organize medical infrastructure.

Low soluble Fas (sFas) and sFas ligand (sFasL) content in breast milk after preterm as opposed to term delivery.

AIM: Various mechanisms of innate immunity and gastrointestinal integrity are potentially affected by soluble Fas (sFas) and sFas ligand (sFasL). Assuming that sFas and sFasL in milk reflect cellular events during lactogenesis, we aimed to assess the impact of premature parturition and duration of lactation on the concentrations of sFas and sFasL in human milk. PATIENTS AND METHODS: The content of the soluble form of the cell surface receptor Fas (sFas) and its natural ligand (sFasL) was measured in human breast milk of 44 healthy mothers after preterm (<35 wk, n=21) and term (>37 wk, n=23) delivery. Milk was furthermore classified as immature breast milk (days 4-7 of lactation) or mature breast milk (days 35-45 of lactation). Breast milk (2-3 ml) was sampled 5 min after the start of breastfeeding by manual expression or milk pump, and stored at -20 degrees C until analysis by an ELISA. RESULTS: sFas and sFasL concentrations were lower in immature milk after preterm compared to term delivery (sFas: 1.71; 1.38-2.47 ng/ml vs 3.03; 2.02-4.30 ng/ml, p < 0.001; sFasL: 0.13; 0.07-0.21 ng/ml vs 0.29; 0.15-0.60 ng/ml, p < 0.001 [median +/- interquartile range]). Mature milk samples, taken 1 mo later from both gestational groups, did not differ in sFas/sFasL content. Soluble Fas was positively correlated with sFasL in the same sample of immature (p < 0.001) and mature human milk (p < 0.05). A positive correlation was found between sFas and sFasL in immature and mature milk samples of the same mother (p < 0.01). The body mass index of the mothers and duration of pregnancy were positively correlated with the sFas and sFasL content in immature milk (p < 0.05 and p < 0.01, respectively) but not in mature milk. CONCLUSION: Preterm newborn infants fed with breast milk have a lower intake of sFas and sFasL compared to term neonates. Our results demonstrate that preterm delivery affects breast milk composition.

Breast milk from mothers of very low birthweight infants: variability in fat and protein content.

UNLABELLED: While breast milk appears to be superior to formula for the development of very low birthweight (VLBW) infants, it is supplemented to meet the metabolic demands of the rapidly growing premature infant. To estimate the nutritional variability of breast milk from mothers of VLBW infants, protein (bicinchoninic acid method) and fat content (creamatocrit) were measured in breast-milk spot samples from mothers of 20 VLBW infants, collected 4 times a day during the first 4 wk of lactation. Protein content (median 1.9 g dl(-1), range 1.1-3.5 g dl(-1)) and fat content (3.8/1.0-14.6 g dl(-1)) were highly variable and lacked a normal distribution over all samples and in individual women's milk. There was only a weak correlation between fat and protein (rs=0.416, p < 0.001). Fat but not protein was lower in morning samples than in samples collected later in the day (p < 0.001). Protein but not fat content decreased during the weeks of lactation (rs =-0.446, p < 0.001). No impact of the baby's gestational age was observed. CONCLUSION: The fat and protein content of breast milk from mothers of VLBW infants is highly variable, calling into question the clinical feasibility of individualized supplementation of breast milk for VLBW infants based on spot sample measurements.

Effects of a low selenium state in patients with phenylketonuria.

Eighty-seven participants of the German Collaboratory Study for Children with Phenylketonuria (PKU) presented low plasma, whole blood and hair selenium (Se) values, reduced urinary selenium excretion, and decreased plasma and erythrocyte glutathione peroxidase activity in comparison with a healthy reference group (all figures p < 0.001). Aspartate amino transferase and thyroxine (T4) concentrations in plasma were inversely correlated with the selenium blood values of the PKU children. Somatic measurements showed a negative standard deviation score of body height in the PKU children compared with reference values. Despite the different Se supply, the infants did not present any specific Se deficiency symptoms.

After-effects of a high altitude expedition on blood.

The aim of the study was to investigate blood alterations caused by altitude acclimatization which last more than few days after return and might play a role for exercise performance at sea level. Measurements were performed in 12 mountaineers before, during and either 7/8 or 11/12 days after a Himalaya expedition (26-29 days at 4900 to 7600 m altitude). [Erythropoietin] rose only temporarily at altitude (max. +11 +/- 1 [SE] mu/ml serum). After return hemoglobin mass (initially 881 +/- 44 g, CO-Hb method) was increased by 14% (p < 0.01); aspartate aminotransferase activity in erythrocytes (initially 682 +/- 25 U/l) was augmented (day 7: +964 +/- 152 U/l, day 11: +533 +/- 107 U/l) indicating reduced mean cell age. Calculated blood volume (+14%) was influenced by red cell formation at altitude but also by plasma expansion at sea level. The half saturation pressure for Hb-O2 (pH 7.4, 37 degrees C) as well as the 2.3-diphosphoglycerate concentration were already initially high (32.1 +/- 0.5 mmHg, 20.5 +/- 0.7 mumol/g Hb) and showed only a nonsignificant tendency to increase after return. Also Hill's n was consistently high in the mountaineers, whereas the Bohr coefficients were slightly increased only after descent. Probably the preparatory physical training, partly in the Alps, and the stay in the Himalaya influenced O2-affinity for a prolonged time. The adaptations might reduce the loss of physical performance capacity at altitude and be part of altitude training effects.

Selenium status in infants and children with phenylketonuria and in maternal phenylketonuria.

The selenium status was investigated in 87 patients of the German Collaborative Study of Phenylketonuria (PKU) (mean age 9.7 years). The selenium values and glutathione peroxidase activity in plasma and erythrocytes were negatively correlated to the quality of dietary management (mean plasma phenylalanine value). Despite a low selenium state, the children showed no clinical sign of deficiency and almost all biochemical parameters checked were normal. In the low selenium state thyroxine values are increased and decline during selenium supplementation, whereas tri-iodothyronine and thyroid stimulating hormone levels remain unchanged. The reduction in glutathione peroxidase activity in plasma was more pronounced than in the erythrocytes pointing to a different availability of both enzymes for selenium. In addition we estimated the selenium status in 29 women with PKU during pregnancy. In 32 healthy pregnant women we observed a decrease in plasma selenium values and the glutathione peroxidase activity in the third trimester, whereas the erythrocyte glutathione peroxidase activity remained stable. In contrast to the healthy women we found in the PKU group a steady decrease of all selenium parameters tested during the whole pregnancy. During the long-term low-dose selenium supplementation in PKU children the glutathione peroxidase activity of plasma and erythrocytes increased. They reached a similar plateau after the application of inorganic or organic selenium compounds. In contrast the selenium values of plasma and whole blood showed only a plateau after the application of sodium selenite. The supplementation with low doses of selenium in the form of selenomethionine increased the plasma and whole blood selenium values constantly within the first 9 months. Therefore selenomethionine supplementation cannot be recommended.

Selenium in German infants fed breast milk or different formulas.

At birth and at 4 months of age, selenium (Se) values of 129 term infants on three different diets were determined: 50 infants were breast fed (HM), 44 received formula based on cow's milk (F) and 35 were fed "hypoallergenic formula" (PHF) (partially hydrolysed whey protein). The Se status of a group of twins (n = 12) fed "hypoallergenic formula" was compared with the respective group of singletons. All infants had low plasma Se values during early infancy. The plasma Se of breast-fed infants remained stable (plasma Se 43 +/- 8 ng/ml at birth and at 4 months), whereas plasma glutathione peroxidase (GSH-Px) decreased (birth: 107 +/- 29 U/l; 4 months: 62 +/- 11 U/l). The formula-fed infants showed a reduction in plasma Se levels from birth to 4 months (38 +/- 10 ng/ml and 29 +/- 9 ng/ml, respectively). The decrease was even more pronounced in infants fed the "hypoallergenic formula". This group presented the lowest Se values (plasma Se 39 +/- 9 ng/ml at birth; 20 +/- 6 ng/ml at 4 months). Renal excretion of Se was found to be lower in the formula-fed infants (F and PHF) compared with the HM group. There was a significant correlation between plasma and urinary Se (r = 0.62, p = 0.0001). Urinary Se (microgram Se/g creatinine) appeared to be a good indicator of Se intake. Measurements of urine Se might be used as a screening method for the estimation of the Se supply. Weight and length increases in all infants were within the normal range. There were no differences between the different feeding groups.

Trace mineral status of full-term infants fed human milk, milk-based formula or partially hydrolysed whey protein formula.

Plasma zinc, copper, and selenium concentrations were determined in 129 full-term infants at birth and at the age of four months by electrothermal or hydride generation atomic absorption spectrometry. Of these, 49 infants were exclusively breast-fed (HM), 45 received various commercially available cow's milk formulae (F) and 35 infants were fed partially hydrolysed whey protein formula (PHF). The results were correlated with hematological, biochemical and somatic data. Plasma zinc values decreased from birth to the age of four months in all three groups (p < 0.001). The plasma Zn level of the babies fed PHF were similar to those of breast-fed infants, whereas in F-fed children the zinc values were significantly lower (PHF, 807 +/- 106; HM, 794 +/- 112; F, 725 +/- 111 micrograms l-1; all the measurements were performed at the age of four months). In infants fed PHF formula there was a negative correlation between plasma zinc and weight or height increments. In agreement with the literature, plasma copper and ceruloplasmin increased significantly within the first four months of life. The plasma copper content was similar in either feeding group. Plasma selenium was low at birth (40 +/- 9 micrograms l-1) and remained constant in breast-fed infants. In infants on PHF there was a steeper decline of plasma Se (20 +/- 6 micrograms l-1) than in infants fed cow's milk formula (29 +/- 9 micrograms l-1). Other parameters of the Se status showed a similar pattern. Despite the different zinc, copper, and selenium supply, plus presumedly different bioavailability, all the infants thrived.(ABSTRACT TRUNCATED AT 250 WORDS)