Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire

We hypothesized that the scarcity of N-nucleotides might contribute to the inability of the neonate to mount a robust allergic immune response. To test this, we used terminal deoxyribunucleotidyl Transferase defcient (TdT−/−) mice, which express “fetal-like” T cell receptor and immunoglobulin repertoires with largely germline-encoded CDR3 regions. Intraperitoneal sensitization was followed by aerosol provocation with either PBS or the allergen OVA in both TdT−/− mice and wild-type mice to develop allergic respiratory infammation. The efects of this procedure were investigated by lung function test, immunological analysis of serum and brochoalveolar lavage. The local TH2 cytokine milieu was signifcantly attenuated in TdT−/− mice. Within this group, the induction of total IgE levels was also signifcantly reduced after sensitization. TdT−/− mice showed a tendency toward reduced eosinophilic infow into the bronchial tubes, which was associated with the elimination of respiratory hyperreactivity. In conclusion, in a murine model of allergic airway infammation, the expression of fetal-like antigen receptors was associated with potent indications of a reduced ability to mount an asthma phenotype. This underlines the importance of somatically-generated antigen-receptor repertoire diversity in type one allergic immune responses and suggests that the fetus may be protected from allergic responses, at least in part, by controlling N addition

Does Maternal Underweight Prior to Conception Influence Pregnancy Risks and Outcome?

While obesity in pregnancy and pregnancy outcome in obese women are subjects of diverse research in recent publications, it is remarkable that the data for pregnancy outcome in pre-conceptional underweight mothers is extremely limited. Apart from an increasing prevalence of obesity, however, the prevalence for underweight in distinct sub-groups of mothers is also increasing. In contrary to obesity, less people are affected by underweight in Europe. The World Health Organization (WHO) classifies human weight into different categories (1). A body mass index (BMI) less than 18.5 kg/m 2 is defined as underweight. In Germany, the incidence of underweight in women is low with a nationwide prevalence of 3% (2). Especially in young women in certain social groups, an anorectic model-like weight is the ideal of beauty and a lot of cases of underweight in women of childbearing age are due to eating disorders (3). The lifetime incidence of eating disorders in young women of childbearing age is 5.2-6.5 % (4). While obesity is a frequently encountered problem in pregnant women with multiple complications during pregnancy and delivery (5-16), data on pregnant women with underweight or anorexia are scarce Because of hormonal disorders due to anorexia, underweight women often have menstrual irregularities leading to amenorrhea and infertility. Disorders in hypothalamic-hypophysis functions result in hypogonadotrope anovulatory cycle

Validity of biomarkers of early circulatory impairment to predict outcome: a retrospective analysis

Objectives: The definition of circulatory impairment in the premature infant is controversial. Current research suggests overdiagnosis and overtreatment. We aimed to analyse which biomarkers move clinicians to initiate cardiovascular treatment (CVT). The prognostic capacity for adverse outcome (death and/or moderate-severe brain damage by cranial ultrasound at term equivalent) of these biomarkers was evaluated. Study Design: Retrospective data analysis from preterm infants enrolled in a placebo-controlled trial on dobutamine for low superior vena cava (SVC) flow, who showed normal SVC flow within the first 24 h (not randomized). Five positive biomarkers were considered: MABP 4 mmol/L; BE < −9 mmol/L; SVC flow <51 ml/kg/min. Results: Ninety eight infants formed the study cohort. Thirty six received CVT (2–95 h). Logistic regression models adjusted for gestational age showed a positive association between CVT and the risk of death or moderate-severe abnormal cranial ultrasound at term equivalent [(OR 5.2, 95%CI: 1.8–15.1) p = 0.002]. MABP 4 mmol/L were the most prevalent biomarkers at start of treatment. Low BE, high serum lactate and low SVC flow at first echocardiography showed a trend toward being associated with adverse outcome, although not statistically significant. Conclusions: Low blood pressure and high lactate are the most prevalent biomarkers used for CVT prescription. Lactic acidosis and low SVC flow early after birth showed a trend toward being associated with adverse outcome. These findings support using a combination of biomarkers for inclusion in a placebo-controlled trial on CVT during transitional circulation

Use of analgesic and sedative drugs in VLBW infants in German NICUs from 2003-2010

Very low birth weight (VLBW) infants frequently receive analgesia and/or sedation for painful procedures and mechanical ventilation to avoid negative stress. Yet, concerns remain regarding potential adverse long-term effects of these drugs on VLBW infants' neurocognitive outcome. Recent studies have shown that less invasive surfactant application (LISA) and early nasal CPAP treatment reduce the need for mechanical ventilation and painful procedures. Therefore, these measures might also reduce the application of analgesic and/or sedative drugs in VLBW infants. To evaluate this hypothesis and to identify potential changes in analgesic treatment concepts in recent years, we retrospectively analyzed data on analgesia and sedation, respiratory support, and the method of surfactant application in VLBW infants enrolled in the German Neonatal Network (GNN) trial between 2003 and 2009 (period 1) and compared it with data from infants participating in GNN in 2010 (period 2). In both periods, about one third of all infants were treated with analgesic and/or sedative drugs using a wide variety of substances. The administration of novel drugs such as propofol, sufentanil, or intravenous paracetamol was higher in 2010 (6.7 vs. 12.2 %). Infants who were treated with CPAP only received significantly less analgesic/sedative medication than infants who were mechanically ventilated (12 vs. 65 %, p = < 0.001). Similarly, infants treated with LISA received less analgesic or sedative drugs as compared to infants who received surfactant via endotracheal intubation (36 vs. 63 %, p = 0.001). Conclusion: Although both avoidances of mechanical ventilation and less invasive surfactant application are associated with reduced analgesic or sedative treatment, the percentage of VLBW infants who received analgesia and/or sedation remained unchanged in Germany in recent years

Monitoring agricultural ecosystems by using wild bees as environmental indicators

Wild bees are abundant in agricultural ecosystems and contribute significantly to the pollination of many crops. The specialisation of many wild bees on particular nesting sites and food resources makes them sensitive to changing habitat conditions. Therefore wild bees are important indicators for environmental impact assessments. Long-term monitoring schemes to measure changes of wild bee communities in agricultural ecosystems are currently lacking. Here we suggest a highly standardized monitoring approach which combines transect walks and pan traps (bowls). The combination of these two methods provides high sample coverage and reveals data on plant-pollinator interactions. We point out that comprehensive methodical, biological and taxonomical expertise is mandatory. The suggested approach is applicable to diverse monitoring goals in an agricultural context e.g. the impact of land use changes as well as monitoring potential effects of GM crops on wild bees

Aminoglycosides were associated with higher rates of surgical patent ductus arteriosus closure in preterm infants

Aim In animal studies, aminoglycosides induced ductus arteriosus relaxation in a dose-dependent fashion. We tested the hypothesis that antibiotic treatment of preterm infants with aminoglycosides is associated with higher rates of surgical patent ductus arteriosus (PDA) closure. Methods Preterm infants (birthweight <1000 grams or gestational age <29 weeks) enrolled in 62 German neonatal intensive care units (NICUs) were analysed. NICUs were stratified according to the use of aminoglycosides as first-line antibiotics. Results Baseline data were not different when NICUs using aminoglycosides (n = 9965 infants) were compared to NICUs using other antibiotics (n = 1948 infants). Rates of surgical PDA closure were 5.9% for NICUs using aminoglycosides; 6.2% for units using gentamicin; and 5.0% for NICUs using tobramycin compared to 4.1% in NICUs using other antibiotics (P < .001,P P = .140, respectively, Fisher's exact test). Indomethacin and ibuprofen use was more common in NICUs using aminoglycosides (41% vs 33%,P < .001, Fisher's exact test). Gentamicin trough levels were higher in NICUs with surgical closure rates above the mean (median 2.0 mu g/mL, inter-quartile range 0.8-4.0 mu g/mL vs 1.2 mu g/mL, IQR 0.8-1.7,P < .001, Mann-WhitneyUtest). Conclusion First-line antibiotic treatment of preterm infants with aminoglycosides was associated with higher rates of surgical PDA closure

Assessment of prognostic factors in pediatric adrenocortical tumors: a systematic review and evaluation of a modified S-GRAS score

ObjectivePediatric adrenocortical carcinoma (pACC) is rare and prognostic stratification remains challenging. We summarized the clinical prognostic factors of pACC and determined the prognostic value of the pediatric scoring system (pS-GRAS) in adaption to the recommendation (S-GRAS) of the European Network for the Study of Adrenal Tumors for the classification of adult ACC. DesignAnalysis of pACC patients of 33 available retrospective studies in the literature. MethodsWe searched the PubMed and Embase databases for manuscripts regarding pACC. The pS-GRAS score was calculated as a sum of tumor stage (1 = 0; 2-3 = 1; 4 = 2 points), grade (Ki67 index/rate of mitosis 0-9%/low = 0; 10-19%/intermediate = 1; >= 20%/high = 2 points), resection status (R0 = 0; RX = 1; R1 = 2; R2 = 3 points), age (= 4 years = 1 point), hormone-related symptoms (androgen production = 0; glucocorticoid/mixed/no hormone production = 1 point) generating 10 scores and 4 groups (1: 0-2, 2: 3-4, 3: 5, 4: 6-9). The primary endpoint was overall survival (OS). ResultsWe included 733 patients. The median age was 2.5 years and >85% of pACC showed hormone activity (mixed 50%, androgen 29%, glucocorticoid 21%). Androgen production was associated with a superior OS. Increasing age correlated with higher rates of inactive or only glucocorticoid-producing tumors, advanced tumor stage, and case fatality. Especially infants < 4 years showed more often low-risk constellations with an increased OS for all tumor stages. The pS-GRAS score correlated with clinical outcome; median OS was 133 months (95% CI: 36-283) in group 1 (n = 49), 110 months (95% CI: 2.9-314) in group 2 (n = 57), 49 months (95% CI: 5.8-278) in group 3 (n = 18), and 16 months (95% CI: 2.4-267) in group 4; (n = 11) P < 0.05). ConclusionThe pS-GRAS score seems to have a high predictive value in the pACC patients, may serve as a helpful tool for risk stratification in future studies, and should be evaluated prospectively in an international context

Less invasive surfactant administration and complications of preterm birth

In a large cohort study of the German Neonatal Network (GNN) we aimed to evaluate whether less invasive surfactant administration (LISA) strategy is associated with complications of preterm birth. Within the observational period n = 7533 very-low-birth-weight infants (VLBWI) with gestational age 22 0/7 to 28 6/7 weeks were enrolled in GNN; n = 1214 VLBWI never received surfactant, n = 2624 VLBWI were treated according to LISA procedure, n = 3695 VLBWI had surfactant via endotracheal tube (ETT). LISA was associated with a reduced risk for adverse outcome measures including mortality [odds ratio (OR) 0.66 (95% CI: 0.51-0.84), p < 0.001] bronchopulmonary dysplasia [BPD; OR 0.55 (95% CI: 0.49-0.62), p < 0.001], intracerebral hemorrhage (ICH) grade II-IV [OR 0.55 (95% CI: 0.48-0.64), p < 0.001] and retinopathy of prematurity [ROP; OR 0.62 (95% CI: 0.45-0.85), p < 0.001]. Notably, LISA was associated with an increased risk for focal intestinal perforation [FIP; OR 1.49 (95% CI: 1.14-1.95), p = 0.002]. The differences in FIP rates were primarily observed in VLBWI born < 26 weeks (LISA: 10.0 vs. ETT: 7.4%, p = 0.029). Our observational data confirm that LISA is associated with improved outcome. In infants < 26 weeks we noted an increased risk for FIP. Future randomized controlled trials including LISA need to integrate safety analyses for this particular subgroup

Two-year outcome data suggest that less invasive surfactant administration (LISA) is safe. Results from the follow-up of the randomized controlled AMV (avoid mechanical ventilation) study

Less invasive surfactant administration (LISA) is a method to deliver surfactant to spontaneously breathing premature infants via a thin catheter. Here we report the two-year outcome from the AMV (avoid mechanical ventilation) study, the first randomized controlled trial on this mode of surfactant delivery. No statistically significant differences in weight, length or neurodevelopmental outcome (Bayley II scores) were found between the LISA intervention group (n = 95) and the control group (n = 84) that received standard treatment. Conclusion: No differences in outcome were observed at 2 years. LISA seems safe in that aspect.What is Known:center dot LISA is a method that is in increasing use for surfactant delivery to spontaneously breathing infants. LISA reduces the need for mechanical ventilation.What is New:center dot Outcome data at 2 years from the first randomized study with LISA raise no safety concerns in comparison to a group of infants that received standard treatment

Adrenocortical Carcinoma in Childhood: A Systematic Review

Simple Summary Pediatric adrenocortical tumors are rare. Little information is available on the incidence, risk factors, prognostic factors, treatment, and overall survival. In this systematic review, we performed a search of the current literature. The most common reported risk factors are age > 4 years, high pathological tumor score, and advanced stage in which prognosis is poor. Treatment options are surgery, radiation, or chemotherapy, but ongoing randomized trials are lacking. International prospective studies must be the next step to implement standardized clinical stratifications and risk-adapted therapeutic strategies. Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89%). Most patients were diagnosed with localized disease, whereas 23% had metastasis at primary diagnosis. Only 72% of the patients achieved complete resection. In 334 children (23%), recurrent disease was reported: 81%-local recurrence, 19% (n = 65)-distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies