Serum cytokines MCP-1 and GCS-F as potential biomarkers in pediatric inflammatory bowel disease.

BACKGROUND: Inflammatory bowel diseases (IBDs) with the subtypes ulcerative colitis (UC) and Crohn disease (CD), are chronic autoimmune inflammatory disorders of the gastrointestinal tract. Cytokines are associated with the development and progression in pediatric IBD. We measured cytokine levels in pediatric IBD patients to assess their potential function as biomarkers in disease assessment. METHOD: In this prospective cohort study, we enrolled 33 children with IBD. All patients were in stable remission for 3 months on enrollment. Patients who developed a relapse within six months after enrollment were classified as relapsers. Blood sampling was performed at enrolment and for relapsers in relapse and post-relapse. Serum concentrations of 14 cytokines, chemokines and growth factors (IL-1α, IL-1ß, IL-6, IL-12p40, IP-10, TNF-α, IFN-γ, IL-10, IL-8, MIP-1α, MCP-1, MCP-3, G-CSF, GM-CSF) were measured simultaneously using multiplex bead-based sandwich immunoassay on Luminex 100 system. RESULTS: MCP-1 was significantly higher in CD patients compared to UC patients at each disease stage: stable remission (P<0.048), unstable remission (P<0.013), relapse (P<0.026) and post-relapse (P<0.024). G-CSF was significantly increased in UC patients developing a relapse and in post-relapse stage compared to UC patients in remission (P<0.02 and p<0.03, respectively). CONCLUSION: MCP-1 showed potential as a diagnostic biomarker in CD patients independent of disease activity as it was able to discriminate between subtypes of pediatric IBD. In UC patients, G-CSF was significantly elevated in relapsers indicating its use and role as a potential prognostic biomarker.

Controlled prospective study on ultrasound simulation training in fetal echocardiography: FESIM II.

PURPOSE: To analyze the learning curves of ultrasound novices in fetal echocardiography during structured simulation-based ultrasound training (SIM-UT) including a virtual, randomly moving fetus. METHODS: 11 medical students with minimal (< 10 h) prior obstetric ultrasound experience underwent 12 h of structured fetal echocardiography SIM-UT in individual hands-on sessions during a 6-week training program. Their learning progress was assessed with standardized tests after 2, 4, and 6 weeks of SIM-UT. Participants were asked to obtain 11 fetal echocardiography standard planes (in accordance with ISUOG and AHA guidelines) as quickly as possible. All tests were carried out under real life, examination-like conditions on a healthy, randomly moving fetus. Subsequently, we analyzed the rate of correctly obtained images and the total time to completion (TTC). As reference groups, 10 Ob/Gyn physicians (median of 750 previously performed Ob/Gyn scans) and 10 fetal echocardiography experts (median of 15,000 previously performed Ob/Gyn scans) were examined with the same standardized tests. RESULTS: The students showed a consistent and steady improvement of their ultrasound performance during the training program. After 2 weeks, they were able to obtain > 95% of the standard planes correctly. After 6 weeks, they were significantly faster than the physician group (p < 0.001) and no longer significantly slower than the expert group (p = 0.944). CONCLUSION: SIM-UT is highly effective to learn fetal echocardiography. Regarding the acquisition of the AHA/ISUOG fetal echocardiography standard planes, the students were able to reach the same skill level as the expert group within 6 weeks.

Serum vascular endothelial growth factor is a potential biomarker for acute mountain sickness.

Background: Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). There is evidence for a role of pro- and anti-inflammatory cytokines in development of AMS, but biological pathways and molecular mechanisms underlying AMS remain elusive. We aimed to measure changes in blood cytokine levels and their possible association with the development of AMS. Method: 15 healthy mountaineers were included into this prospective clinical trial. All participants underwent baseline normoxic testing with venous EDTA blood sampling at the Bangor University in United Kingdom (69 m). The participants started from Beni at an altitude of 869 m and trekked same routes in four groups the Dhaulagiri circuit in the Nepali Himalaya. Trekking a 14-day route, the mountaineers reached the final HA of 5,050 m at the Hidden Valley Base Camp (HVBC). Venous EDTA blood sampling was performed after active ascent to HA the following morning after arrival at 5,050 m (HVBC). A panel of 21 cytokines, chemokines and growth factors were assessed using Luminex system (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-1ra, sIL-2Rα, IFN-γ, TNF-α, MCP-1, MIP-1α, MIP-1ß, IP-10, G-CSF, GM-CSF, EGF, FGF-2, VEGF, and TGF-ß1). Results: There was a significant main effect for the gradual ascent from sea-level (SL) to HA on nearly all cytokines. Serum levels for TNF-α, sIL-2Rα, G-CSF, VEGF, EGF, TGF-ß1, IL-8, MCP-1, MIP-1ß, and IP-10 were significantly increased at HA compared to SL, whereas levels for IFN-γ and MIP-1α were significantly decreased. Serum VEGF was higher in AMS susceptible versus AMS resistant subjects (p < 0.027, main effect of AMS) and increased after ascent to HA in both AMS groups (p < 0.011, main effect of HA). Serum VEGF increased more from SL values in the AMS susceptible group than in the AMS resistant group (p < 0.049, interaction effect). Conclusion: Cytokine concentrations are significantly altered in HA. Within short interval after ascent, cytokine concentrations in HH normalize to values at SL. VEGF is significantly increased in mountaineers suffering from AMS, indicating its potential role as a biomarker for AMS.

Controlled Prospective Study on the Use of Systematic Simulator-Based Training with a Virtual, Moving Fetus for Learning Second-Trimester Scan: FESIM III.

OBJECTIVES: To analyze the feasibility of structured ultrasound simulation training (SIM-UT) in teaching second-trimester ultrasound screening using a high-end simulator with a randomly moving fetus. METHODS: This was a prospective, controlled trial. A trial group of 11 medical students with minimal obstetric ultrasound experience underwent 12 hours of structured SIM-UT in individual hands-on sessions within 6 weeks. Learning progress was assessed with standardized tests. Performance after 2, 4, and 6 weeks of SIM-UT was compared with two reference groups ((A) Ob/Gyn residents and consultants, and (B) highly skilled DEGUM experts). Participants were asked to acquire 23 2nd trimester planes according to ISUOG guidelines in a realistic simulation B-mode with a randomly moving fetus as quickly as possible within a 30-minute time frame. All tests were analyzed regarding the rate of appropriately obtained images and the total time to completion (TTC). RESULTS: During the study, novices were able to improve their ultrasound skills significantly, reaching the physician level of the reference group (A) after 8 hours of training. After 12 hours of SIM-UT, the trial group performed significantly faster than the physician group (TTC: 621±189 vs. 1036±389 sec., p=0.011). Novices obtained 20 out of 23 2nd trimester standard planes without a significant time difference when compared to experts. TTC of the DEGUM reference group remained significantly faster (p<0.001) though. CONCLUSION: SIM-UT on a simulator with a virtual, randomly moving fetus is highly effective. Novices can obtain standard plane acquisition skills close to expert level within 12 hours of self-training.

Patterns of volatile organic compounds in excrements of preterm neonates.

BACKGROUND: As neonates are susceptible for many diseases, establishing noninvasive diagnostic methods is desirable. We hypothesized that volatile organic compounds (VOCs) could be successfully measured in diaper samples. METHODS: We performed a feasibility study to investigate whether ambient air-independent headspace measurements of the VOC profiles of diapers from premature infants can be conducted using ion mobility spectrometer coupled with multi-capillary columns (B & S Analytik GmbH). RESULTS: We analysed 39 diapers filled with stool (n = 10) or urine (n = 20) respectively, using empty diapers as a control (n = 9). A total of 158 different VOCs were identified, and we classified the content of the diapers (urine or stool) according to their VOC profiles with a significance level of p < 0.05. CONCLUSIONS: We have developed a novel method to study headspace VOC profiles of biosamples using ion mobility spectrometry coupled with multi-capillary columns. Using this method, we have characterized the VOC profiles of stool and urine of preterm neonates. Future studies are warranted to characterize specific VOC profiles in infections and other diseases of the preterm neonate, thus establishing quick and noninvasive diagnostics in the routine care of the highly vulnerable preterm and term neonates.

Is There a Role for Cerebral Ultrasonography in Near-Term/Term Neonates Following Assisted Vaginal Delivery? A Prospective, Single-Center Study.

AIM: To evaluate the role of cerebral ultrasonography studies (CUSS) in detecting intracerebral and cranial pathologies (hemorrhages, ischemia, skull fractures) in near-term and term neonates following assisted vaginal delivery. PATIENTS AND METHODS: Prospective single-center study (11/2017-11/2018) at the University Children's Hospital of Saarland, Homburg, Germany including newborns with a gestational age ≥ 36 weeks born by assisted vaginal delivery. In all newborns, a standardized CUSS was performed within the first three days of life prior to discharge. RESULTS: 200 neonates (43.0 % female, 57.0 % male; gestational age 39.6 ±â€Š1.3 weeks) were included in this study (birth weight 3345.6 ±â€Š450.6 g, body length 51.7 ±â€Š2.5 cm, head circumference 35.0 ±â€Š1.5 cm). 67 (33.5 %) neonates had minor external injuries of the scalp. 5 children showed clinical neurologic abnormalities: 4 (2.0 %) seizures and 1 facial palsy (0.5 %). In 34 (17.0 %) patients, minor incidental intracranial abnormalities unrelated to mode of delivery were detected on CUSS. No intracerebral, cranial pathologies or skull fractures were seen on routine CUSS. CONCLUSION: Routine CUSS in newborns after assisted vaginal delivery did not yield clinically relevant results in our cohort. Clinical observation and selective CUSS in symptomatic newborns might be more efficient than routine CUSS.

Neonatal Morbidity and Mortality in Advanced Aged Mothers-Maternal Age Is Not an Independent Risk Factor for Infants Born Very Preterm.

Background: As childbearing is postponed in developed countries, maternal age (MA) has increased over decades with an increasing number of pregnancies between age 35-39 and beyond. The aim of the study was to determine the influence of advanced (AMA) and very advanced maternal age (vAMA) on morbidity and mortality of very preterm (VPT) infants. Methods: This was a population-based cohort study including infants from the "Effective Perinatal Intensive Care in Europe" (EPICE) cohort. The EPICE database contains data of 10329 VPT infants of 8,928 mothers, including stillbirths and terminations of pregnancy. Births occurred in 19 regions in 11 European countries. The study included 7,607 live born infants without severe congenital anomalies. The principal exposure variable was MA at delivery. Infants were divided into three groups [reference 18-34 years, AMA 35-39 years and very(v) AMA ≥40 years]. Infant mortality was defined as in-hospital death before discharge home or into long-term pediatric care. The secondary outcome included a composite of mortality and/or any one of the following major neonatal morbidities: (1) moderate-to-severe bronchopulmonary dysplasia; (2) severe brain injury defined as intraventricular hemorrhage and/or cystic periventricular leukomalacia; (3) severe retinopathy of prematurity; and (4) severe necrotizing enterocolitis. Results: There was no significant difference between MA groups regarding the use of surfactant therapy, postnatal corticosteroids, rate of neonatal sepsis or PDA that needed pharmacological or surgical intervention. Infants of AMA/vAMA mothers required significantly less mechanical ventilation during NICU stay than infants born to non-AMA mothers, but there was no significant difference in length of mechanical ventilation and after stratification by gestational age group. Adverse neonatal outcomes in VPT infants born to AMA/vAMA mothers did not differ from infants born to mothers below the age of 35. Maternal age showed no influence on mortality in live-born VPT infants. Conclusion: Although AMA/vAMA mothers encountered greater pregnancy risk, the mortality and morbidity of VPT infants was independent of maternal age.

Genetic Association With Pseudomonas aeruginosa Acquisition in Cystic Fibrosis: Influence of Surfactant Protein D and Mannose-Binding Lectin.

Background:Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) is associated with poor prognosis. Surfactant protein-D (SFTPD) and mannose-binding lectin (MBL) play a critical role in innate immunity and response to bacterial infections. We investigated serum levels and genetic variants of SFTPD and MBL in CF patients. Method: Thirty-five Caucasian patients homozygous for ΔF508del were genotyped for functional relevant polymorphisms within MBL2 (promoter-221 Y/X, codons 52, 54, and 57) and SFTPD genes (Met11Thr, Ala160Thr, and Ser270Thr). Serum levels of collectins, clinical characteristics, and PA status were correlated with genetic data. Results: Patients age, gender, and PA status did not affect MBL and SFTPD serum concentrations. MBL concentrations were correlated with MBL haplotypes. Patients with chronic Pseudomonas aeroginosa infection (PAC) and MBL insufficiency had a shorter interval between first PA infection and onset of PAC (0.01 vs. 4.6 years, p < 0.04) as well as a lower median age at transition to PAC (9.8 vs. 16.4 years, p < 0.03) compared to MBL sufficient patients with PAC. SFTPD serum level and FEV1% (Spearman r = -0.41, p < 0.03) showed a negative correlation irrespective of PA infection status. The hazard ratio to PA acquisition was increased in carriers of the SFTPD haplotype 11Thr-160Ala-270Ser compared to carriers of the common 11Met-160Thr-270Ser haplotype [HR 3.0 (95%CI: 1.1-8.6), p < 0.04]. Conclusion: MBL insufficiency leads to a shorter interval between first PA infection and onset of chronic infection. Susceptibility to PA acquisition is associated with SFTPD genetic variants with 11Thr-160Ala-270Ser as risk haplotype for early PA infection. This may be due to presence of threonine associated with oligomeric structure of SFTPD and binding ability to bacteria.

Plasma levels of osteopontin from birth to adulthood.

AIM: Osteopontin (OPN) has been investigated as a biomarker for cancer and nonmalignant diseases during the last decades. Data about OPN as a potential biomarker in childhood diseases are still sparse, and reference values are not available in children. We aimed to establish reference values for children from birth to young adulthood and evaluate whether there are age-, gender-, and weight-specific differences. METHOD: Umbilical cord blood and blood plasma samples of 117 children were collected in the Children's Hospital of Saarland University in Homburg/Saar. OPN levels were measured by ELISA, and statistical analysis was performed using SPSS software. RESULTS: Neonates, infants, toddlers, young children, adolescents, and adults were divided into the following six age groups: newborns (birth), infancy and toddlers (0-24 months), early childhood (3-6 years), middle childhood (7-11 years), adolescence (12-18 years), and adults (> 18 years). Highest blood OPN levels were found in the group of 0-1 years of age. OPN blood levels declined significantly with age (Spearman r = -0.874; P < 0.001). CONCLUSION: Our work is the first prospective and systematic study analyzing OPN cord blood and blood plasma levels in children of all ages. It is the first study yielding reference values for different age groups from birth to young adulthood. Our data give insight on how OPN in umbilical cord blood and OPN in blood plasma are physiologically influenced during childhood development and growth with high OPN levels after birth and a constant age-related decline until the age of 14, when OPN levels reach similar values to those measured in adults.

Novel modified Peyton's approach for knowledge retention on newborn life support training in medical students.

AIM: We sought to improve retention of neonatal resuscitation skills by modifying step 3 through additional functional verbalisation in Peyton's four-step approach (P4S). METHODS: Newborn life support (NLS) training was performed in a simulation-based setting. In contrast to the traditional approach, students taught with the modified approach were requested to explain every step of their performance in Peyton's step 3. A total of 123 students were allocated into both experimental groups. Students were then assessed by megacode on day four (initial assessment) and 6 months (follow-up assessment). RESULTS: Both groups showed similar scorings in the initial, follow-up assessment and in mean change. On initial megacode, time to start with initial inflation and post-resuscitation care was significantly faster in the control group. All showed a significant loss of performance irrespective of modification in step 3 in the follow-up assessment. Only time until start with post-resuscitation care shows a significant group difference in mean change between initial and follow-up with increasing time in the control and decreasing time span in intervention group. CONCLUSION: Both methods showed equal levels of knowledge acquisition and long-term decline in NLS performances. Verbalisation in step 3 influenced speed of applied NLS performance.

Long-Term Knowledge Retention after Peer-Assisted Abdominal Ultrasound Teaching: Is PAL a Successful Model for Achieving Knowledge Retention?

BACKGROUND: Diagnostic ultrasound has a crucial importance in clinical settings, especially in intensive care medicine where bedside ultrasound has become indispensable. Medical students as well as residents therefore have a strong interest in learning this useful skill. Since staff resources are limited, more and more universities are using student tutors in a peer-assisted learning concept (PAL) to teach medical students early in their training. To date, there is very sparse data about knowledge retention after peer-assisted teaching. The aim of this study was to evaluate whether PAL is a suitable method for teaching complex skills like abdominal ultrasound and to evaluate whether students do achieve adequate long-term knowledge retention after peer-assisted teaching. METHOD: A total of 40 volunteer 3rd to 5th year students were randomly assigned to a basic abdominal ultrasound course in small training groups of 5 persons each. Participants were evaluated using a pre-post-test design by a validated objective structured clinical examination (OSCE) before and immediately after the course. To measure the retention of knowledge, 15 former participants were randomly selected to repeat the OSCE assessment after one year. RESULTS: All groups showed a significant improvement in practical skills and knowledge gain after the training with mean values of 13.1 for pre-test compared to 83.5 (maximum 100 points) for post-test (p < 0.001). The overall score achieved after one year was 78.7 and did not significantly differ from the post-test result. CONCLUSION: PAL is effective for teaching abdominal ultrasound. Students were able to accomplish a satisfactory level of ultrasound skills. We further demonstrated that PAL can assure long-term knowledge retention.

Bedside Measurement of Volatile Organic Compounds in the Atmosphere of Neonatal Incubators Using Ion Mobility Spectrometry.

Background: Early and non-invasive diagnosis of common diseases is of great importance in the care of preterm infants. We hypothesized that volatile organic compounds (VOC) can be successfully measured in the neonatal incubator atmosphere. Methods: This is a feasibility study to investigate whether the discrimination of occupied and unoccupied neonatal incubators is possible by bedside measurement of volatile organic compounds (VOCs) on the neonatal intensive care unit. VOC profiles were measured in the incubator air using ion mobility spectrometry coupled to multi-capillary columns (BreathDiscovery B&S Analytik GmbH, Dortmund, Germany). Results: Seventeen incubators occupied by preterm infants (50 measurements) and nine unoccupied neonatal incubators were sampled, using 37 room air measurements as controls. Three VOC signals that allow the discrimination between occupied and unoccupied incubators were identified. The best discrimination was reached by peak P20 exhibiting a sensitivity, specificity, positive predictive value and negative predictive value of 94.0, 88.9, 97.3, and 72.3%, respectively. Use of a decision tree improved these values to 100.0, 88.9, 98.0, and 100.0%, respectively. Discussion: A bedside method that allows the characterization of VOC profiles in the neonatal incubator atmosphere using ion mobility spectrometry was established. Occupied and unoccupied incubators could be discriminated by characterizing VOC profiles. This technique has the potential to yield results within minutes. Thus, future studies are recommended to test the hypothesis that VOCs within neonatal incubators are useful biomarkers for non-invasive diagnostics in preterm neonates.

MAGAM II - prospective observational multicentre poisons centres study on eye exposures caused by cleaning products.

Objective: Local effects on the eye following cleaning product exposures are frequently reported. According to EU chemicals legislation many cleaning products are labelled with Hazard Phrase 318 indicating risk of irreversible eye damage. The objectives of this study were to identify cleaning products with potential for irreversible eye damage by collecting human exposure data from poisons centres (PC), and to clarify to what degree exact product identification is possible during a PC telephone call. Methods: MAGAM II was a multicentre binational prospective observational PC study. All human eye exposures to detergents or maintenance products reported to nine PCs taking calls from the public and medical professionals during an 18-month period were included. The severity of eye effects was rated according to the WHO Poisoning Severity Score. Results: Five hundred and eighty-six cases were included. Product identification by name leading to formula information was successful in 533 cases (91%). Follow-up was successful in 528 exposures. Irrigation was performed in 94% of cases. Duration of symptoms was ≥24 hours in 73 patients (25%). 33 (6%) patients developed moderate eye injury. Healing was reported in all cases. The percentage of moderate cases was highest in the group of drain cleaners (25%), toilet cleaners (18%) and oven cleaners (15%). Products intended for professional use caused relatively more moderate eye injuries than products also intended for consumer use. Conclusion: MAGAM II has shown that PCs are able to identify formulas in sufficiently high quality as needed for product-directed toxicovigilance. The results underline the potential of PC exposure case data for product safety monitoring. The results indicate that irreversible eye damage is very rare after cleaning product exposure.

[Intoxications in Children and Adolescents in Germany]. / Deutschlandweites Vergiftungsspektrum im Kindes- und Jugendalter.

BACKGROUND: In Germany, intoxications cause the bulk of emergencies in children, to be prevented or attenuated by preventive measures. Therefore, knowledge about intoxications is essential for pediatricians. The present work provides general and epidemiologic data about intoxications and most frequent categories and single toxicants. METHODS: Data of intoxications in children and adolescents from 6 German poison centers (2012-2016 and 2002-2016) were retrospectively analyzed. Categorical data are given as mean±standard deviation, most frequent toxicants as a score. RESULTS: Calls, especially from non-professionals, increased since 2002. Two third of intoxications occurred in small and pre-school children, more frequently in boys (50%) than girls (44%), in adolescents girls predominated (>60%).<14 years intoxications occur mainly at home, day care or school (>95%), in adolescents suicide attempts and abuse come to the fore (13%). 90% of the cases are asymptomatic or mild, with increasing symptoms at higher ages (adolescents 13% vs. small children 1%). Intoxications with drugs are predominantly in adolescents, surfactant containing cleaning agents and cosmetics, sanitary cleaner, tobacco, glow lights and solute descaler in children. DISCUSSION AND CONCLUSIONS: Increasing incoming calls from professionals and non-professionals point out the importance of the poison centers. Although intoxications in children and adolescents mainly proceed without or mild symptoms, the relevance of preventive measures especially for children<7 should not be underestimated.

Vitamin A Supplementation by Endotracheal Application of a Nano-encapsulated Preparation Is Feasible in Ventilated Preterm Lambs.

BACKGROUND: Vitamin A (VA) is crucial for lung growth and development. In premature infants, inadequate VA levels are associated with an increased risk of bronchopulmonary dysplasia (BPD). Intramuscular VA supplementation has been shown to decrease the incidence of BPD, but is not widely used in the clinical setting due to concerns about feasibility and pain. We studied VA kinetics, distribution, and the induction of early genetic expression of retinoid homeostatic genes in the lung after endotracheal and intravenous application in a preterm lamb model. METHODS: Lambs were delivered prematurely after 85% of gestation, intubated, and ventilated for 3 hours. The animals were randomized to receive no VA ("control"), a bolus of VA intravenously ("i.v."), or VA endotracheally directly after administration of surfactant ("e.t."). RESULTS: Animals treated with VA endotracheally directly after administration of surfactant showed significant increases of VA in serum and lung compared to controls. Animals treated with a bolus of VA intravenously showed significant increases of VA in serum, lung, and liver; however, peak serum concentrations and mRNA levels of homeostatic genes raised concerns about toxicity in this group. CONCLUSIONS: Endotracheal VA supplementation in preterm lambs is feasible and might offer advantages in comparison to i.v. Further studies are warranted to explore biological effects in the context of BPD.

Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung maturation in mice.

BACKGROUND: Oxygen supply as a lifesaving intervention is frequently used to treat preterm infants suffering additionally from possible prenatal or perinatal pathogen features. The impact of oxygen and/or physical lung injury may influence the morphological lung development, leading to a chronic postnatal lung disease called bronchopulmonary dysplasia (BPD). At present different experimental BPD models are used. However, there are no systematic comparative studies regarding different influences of oxygen on morphological lung maturation. OBJECTIVE: We investigated the influence of prenatal hypoxia and/or postnatal hyperoxia on morphological lung maturation based on stereological parameters, to find out which model best reflects morphological changes in lung development comparable with alterations found in BPD. METHODS: Pregnant mice were exposed to normoxia, the offspring to normoxia (No/No) or to hyperoxia (No/Hyper). Furthermore, pregnant mice were exposed to hypoxia and the offspring to normoxia (Hypo/No) or to hyperoxia (Hypo/Hyper). Stereological investigations were performed on all pups at 14 days after birth. RESULTS: Compared to controls (No/No) 1) the lung volume was significantly reduced in the No/Hyper and Hypo/Hyper groups, 2) the volume weighted mean volume of the parenchymal airspaces was significantly higher in the Hypo/Hyper group, 3) the total air space volume was significantly lower in the No/Hyper and Hypo/Hyper groups, 4) the total septal surface showed significantly lower values in the No/Hyper and Hypo/Hyper groups, 5) the wall thickness of septa showed the highest values in the Hypo/Hyper group without reaching significance, 6) the volume density and the volume weighted mean volume of lamellar bodies in alveolar epithelial cells type II (AEII) were significantly lower in the Hypo/Hyper group. CONCLUSION: Prenatal hypoxia and postnatal hyperoxia differentially influence the maturation of lung parenchyma. In 14 day old mice a significant retardation of morphological lung development leading to BPD-like alterations indicated by different parameters was only seen after hypoxia and hyperoxia.

Are Cytokines Useful Biomarkers to Determine Disease Severity in Neonates with Congenital Diaphragmatic Hernia?

Background This study investigates plasma cytokine levels in neonates with the more common left-sided congenital diaphragmatic hernia (CDH) and correlates them with severity of disease indicated by position of the liver. An intrathoracic part of liver is associated with higher need for extracorporeal membrane oxygenation (ECMO) and higher risk for chronic lung disease (CLD). Methods A total of 28 newborns with CDH were subdivided by their liver position in partially intrathoracic (n = 16) and only abdominal (n = 12) position. Only liver-up patients went on ECMO (n = 9) and developed severe/moderate CLD (n = 5). Controls consisted of 19 healthy matched-term neonates. Laboratory samples were extracted from umbilical cord blood and during the neonatal period. Results In umbilical cord blood, CDH patients showed decreased IL-8 values while MIP-1a (macrophage inflammatory protein-1) values were increased. Concerning the severity of CDH, we measured significantly higher levels of TGFb2 in CDH patients with liver-up than in liver-down cases and controls (p < 0.006). During the neonatal period, the concentration of IL-10 and vascular endothelial growth factor (VEGF) showed significant deviations in the liver-up group with need for ECMO (p < 0.009). Conclusion In neonates with CDH, plasma cytokine levels are already altered in utero. TGFb2 may work as an early predictor for severity of disease. VEGF and IL-10 could serve as potential biomarkers predicting the course of disease in CDH.

Severe cyanide poisoning from an alternative medicine treatment with amygdalin and apricot kernels in a 4-year-old child.

BACKGROUND: The use of complementary and alternative medicine (CAM) is widespread in children with cancer and is poorly regulated. PATIENTS AND METHODS: Case report. RESULTS: We describe a case of severe cyanide poisoning arising from CAM use. A severely agitated, encephalopathic, unresponsive 4-year-old boy (initial Glasgow Coma Scale of 3) with a history of metastatic ependymoma was brought to our emergency department by ambulance services. Initial blood gas analysis demonstrated severe metabolic/lactic acidosis. On detailed questioning of the parents, the use of CAM including intravenous and oral "vitamin B 17" (amygdalin) and oral apricot kernel was reported. After administering sodium thiosulfate, rapid improvement in his medical condition with complete recovery without need for further intensive care treatment was seen. Serum cyanide level was markedly elevated. CONCLUSIONS: Cyanide poisoning can be the cause of severe encephalopathy in children receiving CAM treatment with substances containing cyanogenic glycosides.

Human umbilical cord blood mononuclear cells in a double-hit model of bronchopulmonary dysplasia in neonatal mice.

BACKGROUND: Bronchopulmonary dysplasia (BPD) presents a major threat of very preterm birth and treatment options are still limited. Stem cells from different sources have been used successfully in experimental BPD, induced by postnatal hyperoxia. OBJECTIVES: We investigated the effect of umbilical cord blood mononuclear cells (MNCs) in a new double-hit mouse model of BPD. METHODS: For the double-hit, date mated mice were subjected to hypoxia and thereafter the offspring was exposed to hyperoxia. Human umbilical cord blood MNCs were given intraperitoneally by day P7. As outcome variables were defined: physical development (auxology), lung structure (histomorphometry), expression of markers for lung maturation and inflammation on mRNA and protein level. Pre- and postnatal normoxic pups and sham treated double-hit pups served as control groups. RESULTS: Compared to normoxic controls, sham treated double-hit animals showed impaired physical and lung development with reduced alveolarization and increased thickness of septa. Electron microscopy revealed reduced volume density of lamellar bodies. Pulmonary expression of mRNA for surfactant proteins B and C, Mtor and Crabp1 was reduced. Expression of Igf1 was increased. Treatment with umbilical cord blood MNCs normalized thickness of septa and mRNA expression of Mtor to levels of normoxic controls. Tgfb3 mRNA expression and pro-inflammatory IL-1ß protein concentration were decreased. CONCLUSION: The results of our study demonstrate the therapeutic potential of umbilical cord blood MNCs in a new double-hit model of BPD in newborn mice. We found improved lung structure and effects on molecular level. Further studies are needed to address the role of systemic administration of MNCs in experimental BPD.

Bronchopulmonary dysplasia in a double-hit mouse model induced by intrauterine hypoxia and postnatal hyperoxia: closer to clinical features?

Despite increased survival of very preterm newborns, bronchopulmonary dysplasia (BPD) remains a major threat, as it affects long-term pulmonary function and neurodevelopmental outcome. Recent research focused on mechanisms of lung repair. Animal models of BPD in term rodents use postnatal hyperoxia in order to mimic features observed in very preterm human neonates: reduced alveolarization and impaired septal architecture without profound inflammatory changes. In contrast, BPD in very preterm human neonates involves prenatal hits e.g. infections and growth restriction plus postnatal ventilation. BPD induced in rodents by postnatal hyperoxia also exhibits reduced alveolarization however without septal pathology but with marked inflammation. We therefore aimed to establish an animal model combining prenatal growth restriction (FiO2 0.1 for 4 days) with postnatal hyperoxia (FiO2 0.7 for 2 weeks). In double-hit mice the development was retarded: body weight and length, lung and brain weight were significantly reduced by day P14 compared with normoxic controls. Histomorphometric analysis revealed reduced alveolarization and increased septal thickness without pronounced inflammatory lesions. A down-regulation of SftpB and SftpC genes was observed in double-hit animals compared with controls. Thus, we established a new model of BPD using pre- and postnatal hits.