Évaluation de l’effet clinique de la durée d’entreposage des culots érythrocytaires chez les enfants admis aux soins intensifs

Les transfusions de culots érythrocytaires (CE) sont un traitement fréquent en soins intensifs pédiatriques. Des études chez l’adulte suggèrent qu’une durée prolongée d’entreposage des CE est associée à une mauvaise évolution clinique. Aucune étude prospective n’a été conduite en pédiatrie. Notre objectif était d’évaluer l’effet clinique de la durée d’entreposage des CE chez des patients de soins intensifs pédiatriques. Nous avons donc conduit une étude observationnelle prospective dans 30 centres de soins intensifs pédiatriques en Amérique du Nord, chez tous les patients consécutifs de moins de 18 ans, séjournant aux soins intensifs pendant plus de 48 heures. Le critère de jugement primaire était l’incidence de cas de syndrome de défaillance multiviscérale après transfusion. Les critères de jugement secondaire étaient la mortalité à 28 jours et la durée d’hospitalisation aux soins intensifs. En utilisant un modèle de régression logistique, les risques relatifs furent ajustés pour le sexe, l’âge, la sévérité de la maladie à l’admission, le nombre total de transfusions et la dose totale de transfusion. L’étude a montré que les patients recevant des CE entreposés pendant 14 jours ou plus avaient un risque relatif ajusté de 1.87 (IC 95% 1.04 :3.27, p=0.03) de contracter ou de détériorer un syndrome de défaillance multiviscérale après transfusion. Ces mêmes patients avaient une durée d’hospitalisation aux soins intensifs prolongée (+3.7 jours, p<0.001), mais pas de risque augmenté de mortalité. En conclusion, chez les patients de soins intensifs pédiatriques, la transfusion de CE entreposés 14 jours ou plus est associée avec une augmentation de l’incidence de syndrome de défaillance multiviscérale et une durée d’hospitalisation prolongée aux soins intensifs.Transfusion is a common treatment in pediatric intensive care units. Studies in adults suggest that prolonged storage of red blood cell units is associated with worse clinical outcome. No prospective study has been conducted in children. Our objectives were to assess the clinical impact of the length of storage of red blood cell units on clinical outcome in critically ill children. We conducted a prospective, observational study in 30 North American centers, in consecutive patients aged <18 years with a stay ≥48 hours in a pediatric intensive care unit. The primary outcome measure was the incidence of multiple organ dysfunction syndrome after transfusion. The secondary outcomes were 28-day mortality and pediatric intensive care unit length of stay. Odds ratios were adjusted for gender, age, number of organ dysfunctions at admission, total number of transfusions, and total dose of transfusion, using a multiple logistic regression model. Our study showed that for patients receiving blood stored ≥14 days, the adjusted odds ratio for an increased incidence of multiple organ dysfunction syndrome was 1.87 (95% CI 1.04;3.27, p=0.03). There was also a significant difference in the total pediatric intensive care unit length of stay (adjusted median difference +3.7 days, p<0.001) but no significant change in mortality. In critically ill children, transfusion of red blood cell units stored for ≥14 days is independently associated with an increased occurrence of multiple organ dysfunction syndrome and prolonged PICU stay

Transcription factor lineages in plant-pathogenic fungi, connecting diversity with fungal virulence

Plant-pathogenic fungi span diverse taxonomic lineages. Their host-infection strategies are often specialised and require the coordinated regulation of molecular virulence factors. Transcription factors (TFs) are fundamental regulators of gene expression, yet relatively few virulence-specific regulators are characterised in detail and their evolutionary trajectories are not well understood. Hence, this study compared the full range of TFs across taxonomically-diverse fungal proteomes and classified their lineages through an orthology analysis. The primary aims were to characterise differences in the range and profile of TF lineages broadly linked to plant-host association or pathogenic lifestyles, and to better characterise the evolutionary origin and trajectory of experimentally-validated virulence regulators. We observed significantly fewer TFs among obligate, host-associated pathogens, largely attributed to contractions in several Zn2Cys6 TF-orthogroup lineages. We also present novel insight into the key virulence-regulating TFs Ste12, Pf2 and EBR1, providing evidence for their ancestral origins, expansion and/or loss. Ultimately, the analysis presented here provides both primary evidence for TF evolution in fungal phytopathogenicity, as well as a practical phylogenetic resource to guide further detailed investigation on the regulation of virulence within key pathogen lineages

Accuracy of Transcutaneous Carbon Dioxide Measurement in Premature Infants

Background. In premature infants, maintaining blood partial pressure of carbon dioxide (pCO2) value within a narrow range is important to avoid cerebral lesions. The aim of this study was to assess the accuracy of a noninvasive transcutaneous method (TcpCO2), compared to blood partial pressure of carbon dioxide (pCO2). Methods. Retrospective observational study in a tertiary neonatal intensive care unit. We analyzed the correlation between blood pCO2 and transcutaneous values and the accuracy between the trends of blood pCO2 and TcpCO2 in all consecutive premature infants born at <33 weeks’ gestational age. Results. 248 infants were included (median gestational age: 29 + 5 weeks and median birth weight: 1250 g), providing 1365 pairs of TcpCO2 and blood pCO2 values. Pearson’s R correlation between these values was 0.58. The mean bias was −0.93 kPa with a 95% confidence limit of agreement of −4.05 to +2.16 kPa. Correlation between the trends of TcpCO2 and blood pCO2 values was good in only 39.6%. Conclusions. In premature infants, TcpCO2 was poorly correlated to blood pCO2, with a wide limit of agreement. Furthermore, concordance between trends was equally low. We warn about clinical decision-making on TcpCO2 alone when used as continuous monitoring

Effects of Blindfold on Leadership in Pediatric Resuscitation Simulation: A Randomized Trial

Background: Pediatric resuscitations are rare events. Simulation-based training improves clinical and non-clinical skills, as well as survival rate. We assessed the effectiveness of using blindfolds to further improve leadership skills in pediatric simulation-based training.Methods: Twelve teams, each composed of 1 pediatric emergency fellow, 1 pediatric resident, and 2 pediatric emergency nurses, were randomly assigned to the blindfold group (BG) or to the control group (CG). All groups participated in one session of five simulation-based resuscitation scenarios. The intervention was using a blindfold for the BG leader for the scenarios B, C, and D. Three evaluators, who were blinded to the allocation, assessed leadership skills on the first and last video-recorded scenarios (A and E). Questionnaires assessed self-reported changes in stress and satisfaction about skills after the first and the last scenarios.Results: Improvement in leadership skills doubled in the BG compared with the CG (11.4 vs. 5.4%, p = 0.04), whereas there was no increase in stress or decrease in satisfaction.Conclusion: Blindfold could be an efficient method for leadership training during pediatric resuscitation simulated scenarios. Future studies should further assess its effect at a follow-up and on clinical outcomes after pediatric resuscitation

The EO-as-Experimentation perspective: the examination of the entrepreneurial orientation and firm performance/survival relationship

The implications of entrepreneurial orientation (EO) on firm performance have been extensively examined in the literature. However, limited attention has been given to the wide range of performance implications EO may have on shareholder value and financial performance; and the risk of failure created by EO. Instead, current studies have relied on short-term measures of firm performance and focused on a sample of active firms, revealing only the advantageous effects of EO on a firm’s performance as a consequence. This research aims to advance research on EO by examining the effects of EO on firm performance and survival on a separate sample of active and inactive firms in a longitudinal timeframe from the pre-financial crisis period to the post-crisis period. The research aims to reveal new insights into the EO–performance relationship by utilising the EO-as-experimentation perspective

The dark side of EO: Insights into the EO-as-experimentation perspective by investigating the effect of EO on firm performance and failure

The objective of this paper is to advance knowledge on the entrepreneurial orientation (EO) construct and its effect on firm performance and survival. The EO construct has become an essential concept in the entrepreneurship and strategic management literatures, thus it is of significance to pursue. In this paper we provide evidence for the EO-as-experimentation perspective, which has been overlooked by the EO-firm performance literature (Wiklund & Shepherd, 2011). Most of the literature aligns with the EO-as-advantage perspective and considers that EO as a gestalt construct is advantageous to a firm’s performance (Rauch et al., 2009). Overlooking the EO-as-experimentation perspective is dangerous because this perspective predicts a dark side to EO. Furthermore, the results align with the ignored multidimensional view of EO (Lumpkin & Dess, 1996). Here we aim to answer a vital research question: what is the effect of EO and its separate dimensions on firm performance/survival? Unusually, the paper examines the effect of EO on firm performance along a longitudinal timeframe from the pre-crisis (fiscal year 2000) until the post-crisis period (fiscal year 2014). Furthermore, it develops objective proxies to measure the main EO dimensions and considers short term and long term measures of firm performance

Association between length of storage of red blood cell units and outcome of critically ill children: a prospective observational study

INTRODUCTION: Transfusion is a common treatment in pediatric intensive care units (PICUs). Studies in adults suggest that prolonged storage of red blood cell units is associated with worse clinical outcome. No prospective study has been conducted in children. Our objectives were to assess the clinical impact of the length of storage of red blood cell units on clinical outcome of critically ill children. METHODS: Prospective, observational study conducted in 30 North American centers, in consecutive patients aged \u3c18 years with a stay\u3eor= 48 hours in a PICU. The primary outcome measure was the incidence of multiple organ dysfunction syndrome after transfusion. The secondary outcomes were 28-day mortality and PICU length of stay. Odds ratios were adjusted for gender, age, number of organ dysfunctions at admission, total number of transfusions, and total dose of transfusion, using a multiple logistic regression model. RESULTS: The median length of storage was 14 days in 296 patients with documented length of storage. For patients receiving blood stored \u3eor= 14 days, the adjusted odds ratio for an increased incidence of multiple organ dysfunction syndrome was 1.87 (95% CI 1.04;3.27, P = 0.03). There was also a significant difference in the total PICU length of stay (adjusted median difference +3.7 days, P \u3c 0.001) and no significant change in mortality. CONCLUSIONS: In critically ill children, transfusion of red blood cell units stored for \u3eor= 14 days is independently associated with an increased occurrence of multiple organ dysfunction syndrome and prolonged PICU stay

Variability in an effector gene promoter of a necrotrophic fungal pathogen dictates epistasis and effector-triggered susceptibility in wheat

The fungus Parastagonospora nodorum uses proteinaceous necrotrophic effectors (NEs) to induce tissue necrosis on wheat leaves during infection, leading to the symptoms of septoria nodorum blotch (SNB). The NEs Tox1 and Tox3 induce necrosis on wheat possessing the dominant susceptibility genes Snn1 and Snn3B1/Snn3D1, respectively. We previously observed that Tox1 is epistatic to the expression of Tox3 and a quantitative trait locus (QTL) on chromosome 2A that contributes to SNB resistance/susceptibility. The expression of Tox1 is significantly higher in the Australian strain SN15 compared to the American strain SN4. Inspection of the Tox1 promoter region revealed a 401 bp promoter genetic element in SN4 positioned 267 bp upstream of the start codon that is absent in SN15, called PE401. Analysis of the world-wide P. nodorum population revealed that a high proportion of Northern Hemisphere isolates possess PE401 whereas the opposite was observed in representative P. nodorum isolates from Australia and South Africa. The presence of PE401 removed the epistatic effect of Tox1 on the contribution of the SNB 2A QTL but not Tox3. PE401 was introduced into the Tox1 promoter regulatory region in SN15 to test for direct regulatory roles. Tox1 expression was markedly reduced in the presence of PE401. This suggests a repressor molecule(s) binds PE401 and inhibits Tox1 transcription. Infection assays also demonstrated that P. nodorum which lacks PE401 is more pathogenic on Snn1 wheat varieties than P. nodorum carrying PE401. An infection competition assay between P. nodorum isogenic strains with and without PE401 indicated that the higher Tox1-expressing strain rescued the reduced virulence of the lower Tox1-expressing strain on Snn1 wheat. Our study demonstrated that Tox1 exhibits both ‘selfish’ and ‘altruistic’ characteristics. This offers an insight into a complex NE-NE interaction that is occurring within the P. nodorum population. The importance of PE401 in breeding for SNB resistance in wheat is discussed

Performance of the PEdiatric Logistic Organ Dysfunction-2 score in critically ill children requiring plasma transfusions

BACKGROUND: Organ dysfunction scores, based on physiological parameters, have been created to describe organ failure. In a general pediatric intensive care unit (PICU) population, the PEdiatric Logistic Organ Dysfunction-2 score (PELOD-2) score had both a good discrimination and calibration, allowing to describe the clinical outcome of critically ill children throughout their stay. This score is increasingly used in clinical trials in specific subpopulation. Our objective was to assess the performance of the PELOD-2 score in a subpopulation of critically ill children requiring plasma transfusions. METHODS: This was an ancillary study of a prospective observational study on plasma transfusions over a 6-week period, in 101 PICUs in 21 countries. All critically ill children who received at least one plasma transfusion during the observation period were included. PELOD-2 scores were measured on days 1, 2, 5, 8, and 12 after plasma transfusion. Performance of the score was assessed by the determination of the discrimination (area under the ROC curve: AUC) and the calibration (Hosmer-Lemeshow test). RESULTS: Four hundred and forty-three patients were enrolled in the study (median age and weight: 1 year and 9.1 kg, respectively). Observed mortality rate was 26.9 % (119/443). For PELOD-2 on day 1, the AUC was 0.76 (95 % CI 0.71-0.81) and the Hosmer-Lemeshow test was p = 0.76. The serial evaluation of the changes in the daily PELOD-2 scores from day 1 demonstrated a significant association with death, adjusted for the PELOD-2 score on day 1. CONCLUSIONS: In a subpopulation of critically ill children requiring plasma transfusion, the PELOD-2 score has a lower but acceptable discrimination than in an entire population. This score should therefore be used cautiously in this specific subpopulation

A specific fungal transcription factor controls effector gene expression and orchestrates the establishment of the necrotrophic pathogen lifestyle on wheat

The fungus Parastagonospora nodorum infects wheat through the use of necrotrophic efector (NE) proteins that cause host-specifc tissue necrosis. The Zn2Cys6 transcription factor PnPf2 positively regulates NE gene expression and is required for virulence on wheat. Little is known about other downstream targets of PnPf2. We compared the transcriptomes of the P. nodorum wildtype and a strain deleted in PnPf2 (pf2-69) during in vitro growth and host infection to further elucidate targets of PnPf2 signalling. Gene ontology enrichment analysis of the diferentially expressed (DE) genes revealed that genes associated with plant cell wall degradation and proteolysis were enriched in down-regulated DE gene sets in pf2-69 compared to SN15. In contrast, genes associated with redox control, nutrient and ion transport were up-regulated in the mutant. Further analysis of the DE gene set revealed that PnPf2 positively regulates twelve genes that encode efector-like proteins. Two of these genes encode proteins with homology to previously characterised efectors in other fungal phytopathogens. In addition to modulating efector gene expression, PnPf2 may play a broader role in the establishment of a necrotrophic lifestyle by orchestrating the expression of genes associated with plant cell wall degradation and nutrient assimilation.Tis study was supported by the Centre for Crop and Disease Management, a joint initiative of Curtin University and the Grains Research and Development Corporation [research grant CUR00023 (Programme 3)]. EJ was supported by the Australian Government Research Training Program Scholarshi