Improved Macro- and Micronutrient Supply for Favorable Growth and Metabolomic Profile with Standardized Parenteral Nutrition Solutions for Very Preterm Infants.

Very preterm infants are at high risk for suboptimal nutrition in the first weeks of life leading to insufficient weight gain and complications arising from metabolic imbalances such as insufficient bone mineral accretion. We investigated the use of a novel set of standardized parenteral nutrition (PN; MUC PREPARE) solutions regarding improving nutritional intake, accelerating termination of parenteral feeding, and positively affecting growth in comparison to individually prescribed and compounded PN solutions. We studied the effect of MUC PREPARE on macro- and micronutrient intake, metabolism, and growth in 58 very preterm infants and compared results to a historic reference group of 58 very preterm infants matched for clinical characteristics.

Polychlorinated dioxins and dibenzofurans (PCDD/F), polybrominated dioxins and dibenzofurans (PBDD/F), polychlorinated biphenyls (PCB), polybrominated diphenyl ethers (PBDE), and per- and polyfluoroalkyl substances (PFAS) in German breast milk samples (LUPE 8).

Most organic pollutants (POP) are persistent in the environment, accumulate in fatty tissues, and so a transfer through the food chain is probably, thereby causing various health effects. We quantified PCDD/F, PBDD/F, PCB, PBDE, perfluorinated substances, and ADONA in breast milk samples collected in two German federal states and breast milk and blood samples from subjects additionally exposed to PFOA. The median (95th percentile) concentrations were 2.

Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure -A clinical practice Guideline Level 3.

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno-arterial extracorporeal membrane oxygenation (va-ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio-economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline].

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF).

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline].

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF).

[Long-Term Development of Infants after Extracorporeal Membrane Oxygenation (ECMO)].

Background: After neonatal lung failure and especially after ECMO therapy long-term morbidities are common. The follow-up of these seriously ill neonates is an indispensable quality criterion for an ECMO centre and beyond that follow-up data are important for counselling parents. Yet, ECMO-centres often cover a large service area and follow-up is difficult due to long travel distances for parents.

Multicenter Experience With Mechanical Circulatory Support Using a New Diagonal Pump in 233 Children.

Technological innovations in pediatric extracorporeal life support circuits can reduce system-related complications and may improve patients' outcome. The Deltastream DP3 (Medos Medizintechnik AG, Stolberg, Germany) is a novel rotational pump with a diagonally streamed impeller that can be used over a broad range of flows. We collected patient data from seven pediatric centers to conduct a retrospective cohort study.

Antenatal BAY 41-2272 reduces pulmonary hypertension in the rabbit model of congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) fail to adapt at birth because of persistent pulmonary hypertension (PH), a condition characterized by excessive muscularization and abnormal vasoreactivity of pulmonary vessels. Activation of soluble guanylate cyclase by BAY 41-2272 prevents pulmonary vascular remodeling in neonatal rats with hypoxia-induced PH. By analogy, we hypothesized that prenatal administration of BAY 41-2272 would improve features of PH in the rabbit CDH model.

Increased TGF-β: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

Survivors of severe congenital diaphragmatic hernia (CDH) present significant respiratory morbidity despite lung growth induced by fetal tracheal occlusion (TO). We hypothesized that the underlying mechanisms would involve changes in lung extracellular matrix and dysregulated transforming growth factor (TGF)-β pathway, a key player in lung development and repair. Pulmonary expression of TGF-β signaling components, downstream effectors, and extracellular matrix targets were evaluated in CDH neonates who died between birth and the first few weeks of life after prenatal conservative management or TO, and in rabbit pups that were prenatally randomized for surgical CDH and TO vs.

Intrapulmonary instillation of perflurooctylbromide improves lung growth, alveolarization, and lung mechanics in a fetal rabbit model of diaphragmatic hernia.

Objectives: Fetal tracheal occlusion of hypoplastic rabbit lungs results in lung growth and alveolarization although the surfactant protein messenger RNA expression is decreased and the transforming growth factor-β pathway induced. The prenatal filling of healthy rabbit lungs with perfluorooctylbromide augments lung growth without suppression of surfactant protein synthesis. We hypothesizes that Intratracheal perfluorooctylbromide instillation improves lung growth, mechanics, and extracellular matrix synthesis in a fetal rabbit model of lung hypoplasia induced by diaphragmatic hernia.

Long-term outcome at age 7-10 years after extreme prematurity - a prospective, two centre cohort study of children born before 25 completed weeks of gestation (1999-2003).

Objective: We aimed to determine the long-term neurodevelopmental outcome in extremely preterm infants of 22-23 completed weeks' gestation as compared to infants of 24 weeks with immediate postnatal life support born in two German tertiary perinatal centres between 1999 and 2003.

Methods: Children were assessed for cognitive and neurological outcomes at the age of 7-10 years. The test battery included a neurological examination, the Wechsler Intelligence Scale for children (WISC-IV) and the Frostigs Developmental Test of Visual Perception (DTVP-2).

Abca3 haploinsufficiency is a risk factor for lung injury induced by hyperoxia or mechanical ventilation in a murine model.

Background: Heterozygous ATP-binding-cassette subfamily A member 3 (ABCA3) mutations are associated with neonatal respiratory complications. In an adult murine model, we investigated whether Abca3 haploinsufficiency is a predisposing factor for lung injury induced by hyperoxia or mechanical ventilation.

Methods: Abca3 haploinsufficient (Abca3(+/-)) and wild-type (WT) mice were prospectively randomized to 25 min of ventilation or 72 h of hyperoxia or left unchallenged in air.

Alveolarization genes modulated by fetal tracheal occlusion in the rabbit model for congenital diaphragmatic hernia: a randomized study.

Background: The mechanisms by which tracheal occlusion (TO) improves alveolarization in congenital diaphragmatic hernia (CDH) are incompletely understood. Therefore transcriptional and histological effects of TO on alveolarization were studied in the rabbit model for CDH. The question of the best normalization strategy for gene expression analysis was also addressed.

SFTA2--a novel secretory peptide highly expressed in the lung--is modulated by lipopolysaccharide but not hyperoxia.

Tissue-specific transcripts are likely to be of importance for the corresponding organ. While attempting to define the specific transcriptome of the human lung, we identified the transcript of a yet uncharacterized protein, SFTA2. In silico analyses, biochemical methods, fluorescence imaging and animal challenge experiments were employed to characterize SFTA2.

Expression of therapeutic proteins after delivery of chemically modified mRNA in mice.

Current viral vectors for gene therapy are associated with serious safety concerns, including leukemogenesis, and nonviral vectors are limited by low gene transfer efficiency. Here we investigate the therapeutic utility of chemically modified mRNA as an alternative to DNA-based gene therapy. A combination of nucleotide modifications abrogates mRNA interaction with Toll-like receptor (TLR)3, TLR7, TLR8 and retinoid-inducible gene I (RIG-I), resulting in low immunogenicity and higher stability in mice.

Comparison of lung accumulation of cationic liposomes in normal rats and LPS-treated rats.

Objective: Cationic liposomes have been shown to target angiogenic endothelial cells in lungs and joints with evidence of chronic inflammation. We sought to determine whether cationic liposomes accumulate in acutely inflamed lung tissue. SUBJECTS, TREATMENT AND METHODS: Acute lung injury was induced by intratracheal instillation of lipopolysaccharide (LPS) in Sprague Dawley rats.

Electrical impedance tomography is able to track changes in respiratory function in endotoxin-challenged rodents.

Background And Objective: In order to assess and optimize the effect of new therapies for acute lung injury (ALI) in rodent models, a monitoring technique that continuously assesses the functional state of the lung is mandatory. Electrical impedance tomography (EIT) has been suggested as a technique for quantifying lung inflammation in ALI. However, EIT has not been evaluated in a rodent model of ALI.

Limitation of measurements of expiratory tidal volume and expiratory compliance under conditions of endotracheal tube leaks.

Objective: Endotracheal tube leaks (ETTLs) occur in neonates ventilated with uncuffed tubes. Assuming that the influence of ETTLs might be neglected during expiration, only expiratory tidal volume is measured for calculation of expiratory compliance in cases of large ETTLs. However, expiratory ETTL might be substantial.

Calculation of intratracheal airway pressure in ventilated neonatal piglets with endotracheal tube leaks.

Objective: In ventilated neonates, only the applied pressure of the ventilator is adjusted and monitored. When an endotracheal tube leaks, intratracheal pressure decreases depending on the size of the endotracheal tube and of the leak. Furthermore, an increase in resistance and/or compliance might delay the increase of intratracheal pressure during inspiration and its decline during expiration.

Survival and major neonatal complications in infants born between 22 0/7 and 24 6/7 weeks of gestation (1999-2003).

Objective: This study was undertaken to compare survival and morbidity until discharge in infants born after 22-23 versus 24 weeks' gestational age (GA).

Study Design: Cohort study of all infants 25 weeks or less, born in 3 tertiary perinatal centers (1999-2003).

Results: Of a total of 336 infants, 133 (40%) died before or immediately after birth without the provision of life support, 203 (60%) received active neonatal treatment.