Search

Purpose: Very low birth weight (VLBW) infants are at a risk of spontaneous focal intestinal perforation (FIP). Treatment includes supportive care, antibiotics, and drainage with/without surgery. Broad-spectrum antibiotic agents like carbapenems are applied frequently, although their use is not well-supported by the limited evidence of causal pathogens. We hypothesize that the use of carbapenems may not be necessary in VLBW infants with FIP. Our primary objective was to evaluate the antimicrobial use in VLBW infants with FIP in a cohort of the German Neonatal Network (GNN). The secondary objective was to characterize a subset in detail as a benchmark for future targets of stewardship. Methods: Data on VLBW infants with FIP was collected prospectively within the GNN, a collaboration of 68 neonatal intensive care units (NICU). With regards to the primary objective, patient characteristics and antimicrobial treatment were extracted from the predefined GNN database. To address our secondary objective, an additional on-site assessment of laboratory and microbiological culture results were performed. Results: In the GNN cohort, 613/21,646 enrolled infants (2.8%) developed FIP requiring surgery. They were frequently treated with carbapenems (500/613 (81.6%)) and vancomycin (497/613 (81.1%)). In a subset of 124 VLBW infants, 77 (72.6%) had proof of gram-positive bacteria in the abdominal cavity, coagulase-negative staphylococci (CoNS) predominantly. Despite the low prevalence of gram-negative bacteria (n = 6 (4.8%)), the combination of meropenem and vancomycin was prescribed most frequently (n = 96 (78.0%)). Conclusion: The use of carbapenems as broad-spectrum antimicrobials agents might not be justified in most VLBW infants with FIP. Knowledge on the development of the neonatal gut microbiota, local resistance patterns and individual microbiological findings should be taken into consideration when implementing antimicrobial stewardship programs (ASPs). [ABSTRACT FROM AUTHOR]

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage °3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28 days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%).Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed. What is Known:• Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies.• Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. What is New:• This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects.• The hypothesis is generated that nasal breast milk might exert neuroprotective effects in preterm infants. [ABSTRACT FROM AUTHOR]

Unlabelled: 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. [ABSTRACT FROM AUTHOR]

Unlabelled: The number of reports on baclofen intoxication has increased in recent years. We report a 15-year-old boy who was referred in a state of deep coma (Glasgow Coma Scale = 3). On clinical examination, he showed sinus bradycardia with normal blood pressure. On admission to the hospital, he presented intermittent short episodes of generalized tonic-clonic seizures. While results of imaging procedures and initial toxicological screening (including standard HPLC analysis and urine test) were negative, a nonconvulsive status epilepticus was diagnosed by electroencephalography (EEG). Identification of baclofen as causative agent was possible after the boy's father reported abusive baclofen intake. Subsequent toxicological target analysis of blood and urine samples confirmed the excessive intake of baclofen and showed a typical elimination pattern with a secondary release. Following 112 h of mechanical ventilation, the boy rapidly regained consciousness and recovered normal neurological behavior.Conclusions: The present case demonstrates the importance of considering baclofen overdosage in cases of severe coma in combination with an abnormal EEG pattern and sinus bradycardia with normal blood pressure levels, in particular as the substance is popular in internet reports promoting baclofen as a rather harmless "fun drug." Furthermore, it underlines the difficulty to identify baclofen as a causative agent without anamnestic information. Nevertheless, by reviewing existing literature on oral baclofen overdosage, it is possible to picture a nearly specific pattern of clinical symptoms in baclofen intoxication. [ABSTRACT FROM AUTHOR]

Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis. [ABSTRACT FROM AUTHOR]

The anaplastic lymphoma kinase (ALK) gene has been found either rearranged or mutated in several neoplasms such as anaplastic large-cell lymphoma, non-small-cell lung cancer, neuroblastoma and anaplastic thyroid cancer. Medulloblastoma (MB) is an embryonic pediatric cancer arising from nervous system, a tissue in which ALK is expressed during embryonic development. We performed an ALK mutation screening in 52 MBs and we found a novel heterozygous germline deletion of a single base in exon 23 (3605delG) in a case with marked anaplasia. This G deletion results in a frameshift mutation producing a premature stop codon in exon 25 of ALK tyrosine kinase domain. We also screened three human MB cell lines without finding any mutation of ALK gene. Quantitative expression analysis of 16 out of 52 samples showed overexpression of ALK mRNA in three MBs. In the present study, we report the first mutation of ALK found in MB. Moreover, a deletion of ALK gene producing a stop codon has not been detected in human tumors up to now. Further investigations are now required to elucidate whether the truncated form of ALK may have a role in signal transduction. [ABSTRACT FROM AUTHOR]

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage °3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28 days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%).Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed. What is Known: • Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies. • Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. What is New: • This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects. • The hypothesis is generated that nasal breast milk might exert neuroprotective effects in preterm infants. [ABSTRACT FROM AUTHOR]