According to the published report on current practice of hematopoietic SCT in Europe, high-dose therapy (HDT) with autologous stem cell support is a standard of care in paediatric patients with high risk (HR) or relapsed Ewing's sarcoma (ES). Randomized trials, however, have not confirmed the value of this procedure yet. In this retrospective analysis we intended to evaluate the role of HDT as a consolidation therapy in first remission of ES. A total of 102 patients were included in the analysis and divided according to the following risk factors: metastatic disease at presentation, feasibility of surgery and histological response after induction. Forty-one patients were classified as standard risk (SR) patients, while the remaining 61 children, with at least one risk factor, were classified as HR patients. HR group patients were non-randomized and qualified according to the decision of the local clinician to give a conventional consolidation (CC) or to perform high-dose chemotherapy and radiotherapy in selected patients. Twenty-six children were given CC while 35 patients were treated with HDT. The HDT consisted of oral BU 4 mg/kg p.o. in divided doses daily for 4 days (total dose 16 mg/kg) followed by melphalan 140 mg/m(2) i.v. on day -2. Probability of relapse-free survival (RFS) in median observation time was significantly worse in HR patients who were given CC therapy as compared with children with HR features receiving high-dose chemotherapy (0.27 vs 0.66 (P=0.008); OS 0.31 vs 0.71 (P=0.007), respectively). Patients from the SR group had a probability of RFS of 0.72 and OS of 0.75, and the difference between SR and HR patients after HDT was NS (P=0.37). Our observation confirms that the consolidation of the first-line treatment with BU and melphalan improves the outcome in ES patients with HR features.Bone Marrow Transplantation advance online publication, 21 May 2012; doi:10.1038/bmt.2012.78.

ABSTRACT: INTRODUCTION: The present study is a pilot prospective safety evaluation of a new closed loop computerized protocol on ventilation and oxygenation in stable, spontaneously breathing children weighting more than 7kg, during the weaning phase of mechanical ventilation. METHODS: Mechanically ventilated children ready to start the weaning process were ventilated for 5 periods of 60 minutes in the following order: Pressure Support Ventilation (PSV), Adaptive Support Ventilation (ASV), ASV plus a ventilation controller (ASV-CO2), ASV-CO2 plus an oxygenation controller (ASV-CO2-O2) and PSV again. Based on breath by breath analysis, the percentage of time with normal ventilation as defined by a respiratory rate (RR) between 10 and 40 breath/min, a tidal volume (VT)> 5 ml/kg of predicted body weight and an end tidal CO2 between 25 and 55 mmHg. The number of manipulations and changes on the ventilator were also recorded. RESULTS: Fifteen children, median aged 45 months, were investigated. No adverse event and no premature protocol termination were reported. ASV-CO2 and ASV-CO2-O2, kept the patients within normal ventilation for respectively 94%[91 - 96] and 94%[87 - 96]) of the time. VT, RR, Peak inspiratory airway pressure (Paw-peak) and minute ventilation were equivalent with all modalities, although there were more automatic setting changes in ASV-CO2 and ASV-CO2-O2. PEEP modifications by ASV-CO2-O2 needs further investigation. CONCLUSIONS: Over the short study period and in this specific population, ASV-CO2 and ASV-CO2-O2 were safe and kept the patient with normal ventilation most of the time. Further research is needed, especially for PEEP modifications by ASV-CO2-O2. Trial registration: NCT01095406.

In the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelated donor (MUD) between 2000 and 2009 were evaluated. Engraftment was achieved in 45 (93.75 %) patients after MSD-hematopoietic stem cell transplantation (HSCT) and in 33 (86.8 %) after MUD-HSCT. Transplant-related mortality rate after MSD-HSCT was 8 %, while 37 % after MUD-HSCT. After MSD-HSCT 44 (91.7 %) patients are alive for 1-216 months (median: 85 months), while after MUD-HSCT 24 (63.2 %) patients for 1-84 months (median: 16 months). The 5-year probability of event-free survival after MSD-HSCT and MUD-HSCT was 87 and 53 %, respectively, while 5 years of overall survival was 91 and 64 %, respectively. It was concluded that MSD-HSCT as the first line treatment for children with SAA is a safe therapeutic approach with a low rate of treatment failures and excellent outcome. Results of MUD-HSCT in pediatric patients with SAA who failed to respond to immunosuppressive therapy are still inferior than those of MSD-HSCT. Treatment failures of MUD-HSCT are mainly related to infectious complications and graft failure. It seems, however, that HLA-matching of unrelated donors at allelic level along with early MUD-HSCT after FCA (FLUDA, low-dose cyclophosphamide, and anti-thymocyte globulin) conditioning, perhaps using lower Thymoglobulin dose could enable further improvement of long-term results in children with SAA who lack MSD.

Differences in gene expression were compared between RNAs from lungs of high (HR) and low (LR) porcine reproductive and respiratory syndrome virus (PRRSV) burden pigs using the swine protein-annotated long oligonucleotide microarray, the Pigoligoarray. Pathway analyses were carried out to determine biological processes, pathways and networks that differ between the LR and HR responses. Differences existed between HR and LR pigs for 16 signalling pathways [P < 0.01/-log (P-value)>1.96]. Top canonical pathways included acute phase response signalling, crosstalk between dendritic cells and natural killer cells and tight junction signalling, with numerous immune response genes that were upregulated (SOCS1, SOD2, RBP4, HLA-B, HLA-G, PPP2R1A and TAP1) or downregulated (IL18, TF, C4BPA, C1QA, C1QB and TYROBP). One mechanism, regulation of complement activation, may have been blocked in HR (PRRSV-susceptible) pigs and could account for the poor clearance of PRRSV by infected macrophages. Multiple inhibiting signals may have prevented effective immune responses in susceptible HR pigs, although some protective genes were upregulated in these pigs. It is likely that in HR pigs, expression of genes associated with protection was delayed, so that the immune response was not stimulated early; thus, PRRSV infection prevented protective immune responses.

PURPOSE: IntelliVent-ASV(®) is a development of adaptive support ventilation (ASV) that automatically adjusts ventilation and oxygenation parameters. This study assessed the safety and efficacy of IntelliVent-ASV(®) in sedated intensive care unit (ICU) patients with acute respiratory failure. METHODS: This prospective randomized crossover comparative study was conducted in a 12-bed ICU in a general hospital. Two periods of 2 h of ventilation in randomly applied ASV or IntelliVent-ASV(®) were compared in 50 sedated, passively ventilated patients. Tidal volume (V (T)), respiratory rate (RR), inspiratory pressure (P (INSP)), SpO(2) and E(T)CO(2) were continuously monitored and recorded breath by breath. Mean values over the 2-h period were calculated. Respiratory mechanics, plateau pressure (P (PLAT)) and blood gas exchanges were measured at the end of each period. RESULTS: There was no safety issue requiring premature interruption of IntelliVent-ASV(®). Minute ventilation (MV) and V (T) decreased from 7.6 (6.5-9.5) to 6.8 (6.0-8.0) L/min (p < 0.001) and from 8.3 (7.8-9.0) to 8.1 (7.7-8.6) mL/kg PBW (p = 0.003) during IntelliVent-ASV(®) as compared to ASV. P (PLAT) and FiO(2) decreased from 24 (20-29) to 20 (19-25) cmH(2)O (p = 0.005) and from 40 (30-50) to 30 (30-39) %(p < 0.001) during IntelliVent-ASV(®) as compared to ASV. RR, P (INSP), and PEEP decreased as well during IntelliVent-ASV(®) as compared to ASV. Respiratory mechanics, pH, PaO(2) and PaO(2)/FiO(2) ratio were not different but PaCO(2) was slightly higher during IntelliVent-ASV(®) as compared to ASV. CONCLUSIONS: In passive patients with acute respiratory failure, IntelliVent-ASV(®) was safe and able to ventilate patients with less pressure, volume and FiO(2) while producing the same results in terms of oxygenation.

The aim of the present study was to examine the relationship of changes in long term glucose levels as measured by Hemoglobin A1c (HbA1c) with simultaneous changes in cognition. The sample included in the present analysis consisted of 101 community dwelling non-diabetic elderly subjects participating in ongoing longitudinal studies of cognition. Subjects were included in this study if they were cognitively normal at baseline, had at least one co-temporaneous follow-up assessment of HbA1c and the Mini Mental State Exam (MMSE), and complete data on age, gender, race, and years of education. MMSE decline over time was the main outcome measure. In TOBIT mixed regression models, MMSE was the dependent variable and HbA1c the time-varying covariate. Sociodemographic (age, gender, and education), cardiovascular (hypertension and APOE4 status), and lifestyle (smoking and physical activity) covariates were included in the statistical model. After adjusting for age at follow-up, there was a decrease of 1.37 points in the MMSE (p = 0.0002) per unit increase in HbA1c. This result remained essentially unchanged after adjusting also for gender and education (p = 0.0005), cardiovascular factors (p = 0.0003), and lifestyle (p = 0.0006). Additionally, results remained very similar after excluding subjects with potentially incipient diabetes with HbA1c between 6 and 7. These findings suggest that in non-diabetic non-demented elderly subjects, an increase in HbA1c over time is associated with cognitive decline. Such results may have broad clinical applicability since manipulation of glucose control, even in non-diabetics, may affect cognitive performance, perhaps enabling preventive measures against dementia.

AIM Identification of signal transduction genes related to drug resistance in pediatric acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS Ex vivo drug resistance in 107 children, divided into study and validation groups, was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) drug resistance assay. The gene expression profile was identified by microarray analysis and validated by quantitative reverse transcription polymerase chain reaction. RESULTS A set of five genes involved in signal transduction, present in each resistance profile, was identified. The expression of four genes was up-regulated: Gardner-Rasheed feline sarcoma viral oncogene homolog, v-Fgr (FGR), S100 calcium binding protein A11 (S100A11), formyl peptide receptor 1 (FPR1), ArfGAP with RhoGAP domain, ankyrin repeat and PH1 domain (ARAP1), while the expression of growth hormone 1 (GH1) was found to be down-regulated in resistant leukemia blasts. CONCLUSION Ex vivo exposure of leukemia cells to anticancer drugs induces changes in the expression of genes involved in cell signaling pathways. These genes play an important role in the mechanism of cellular drug resistance.

Flow coefficients v_{n} for n=2, 3, 4, characterizing the anisotropic collective flow in Au+Au collisions at sqrt[s_{NN}]=200  GeV, are measured relative to event planes Ψ_{n}, determined at large rapidity. We report v_{n} as a function of transverse momentum and collision centrality, and study the correlations among the event planes of different order n. The v_{n} are well described by hydrodynamic models which employ a Glauber Monte Carlo initial state geometry with fluctuations, providing additional constraining power on the interplay between initial conditions and the effects of viscosity as the system evolves. This new constraint can serve to improve the precision of the extracted shear viscosity to entropy density ratio η/s.

ABSTRACT: Mechanical ventilation can be perceived as a treatment with a very narrow therapeutic window, i.e., highly efficient but with considerable side effects if not used properly and in a timely manner. Protocols and guidelines have been designed to make mechanical ventilation safer and protective for the lung. However, variable effects and low compliance with use of written protocols have been reported repeatedly. Use of explicit computerized protocols for mechanical ventilation might very soon become a "must." Several closed loop systems are already on the market, and preliminary studies are showing promising results in providing patients with good quality ventilation and eventually weaning them faster from the ventilator. The present paper defines explicit computerized protocols for mechanical ventilation, describes how these protocols are designed, and reports the ones that are available on the market for children.

Back-to-back hadron pair yields in d+Au and p+p collisions at √s(NN)=200 GeV were measured with the PHENIX detector at the Relativistic Heavy Ion Collider. Rapidity separated hadron pairs were detected with the trigger hadron at pseudorapidity |η|<0.35 and the associated hadron at forward rapidity (deuteron direction, 3.0<η<3.8). Pairs were also detected with both hadrons measured at forward rapidity; in this case, the yield of back-to-back hadron pairs in d+Au collisions with small impact parameters is observed to be suppressed by a factor of 10 relative to p+p collisions. The kinematics of these pairs is expected to probe partons in the Au nucleus with a low fraction x of the nucleon momenta, where the gluon densities rise sharply. The observed suppression as a function of nuclear thickness, p(T), and η points to cold nuclear matter effects arising at high parton densities.