Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Seed limitation interacts with biotic and abiotic factors to constrain novel species' impact on community biomass and richness

Seed limitation can narrow down the number of coexisting plant species, limit plant community productivity, and also constrain community responses to changing environmental and biotic conditions. In a 10-year full-factorial experiment of seed addition, fertilisation, warming and herbivore exclusion, we tested how seed addition alters community richness and biomass, and how its effects depend on seed origin and biotic and abiotic context. We found that seed addition increased species richness in all treatments, and increased plant community biomass depending on nutrient addition and warming. Novel species, originally absent from the communities, increased biomass the most, especially in fertilised plots and in the absence of herbivores, while adding seeds of local species did not affect biomass. Our results show that seed limitation constrains both community richness and biomass, and highlight the importance of considering trophic interactions and soil nutrients when assessing novel species immigrations and their effects on community biomass.Peer reviewe

Both diversity and functional composition affect productivity and water use efficiency in experimental temperate grasslands

Many experiments have shown that biodiversity promotes ecosystem functioning and stability and that this relationship varies with resource availability. However, we still have a poor understanding of the underlying physiological and ecological mechanisms driving diversity effects and how they may interact with soil nutrient availability. We collected data in a grassland experiment factorially manipulating fertilization, species richness (SR), functional composition (slow-growing vs. fast-growing species) and functional diversity in resource economic traits. We measured above-ground productivity (AP), nitrogen (N) uptake, photosynthesis and water use efficiency by combining a N-15 labelling approach with productivity, gas exchange and stable isotope measurements in 3 years differing in rainfall. We found that sown SR increased AP, N uptake and photosynthesis, suggesting that SR is the most important driver of ecosystem productivity and nutrient cycling. Similarly, photosynthesis was affected by functional composition but not by functional diversity. Water use efficiency was reduced by sown SR for communities dominated by slow-growing species but not for communities dominated by fast-growing species. Fertilization increased productivity, N uptake and water use efficiency. The positive effects of high SR on ecosystem functions were independent of fertility levels. Synthesis. Our results provide evidence that high species richness in temperate grasslands could enhance productivity and reduce the negative impacts of drought events. Multiple factors and community characteristics are important in driving enhanced ecosystem functioning in biodiverse grasslands and seem to affect functioning and stability through different mechanisms.Peer reviewe

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

Background: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. Methods: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. Results: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04-1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15-1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7-3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64-7.71) and mortality (RR=19.80; 95% CI, 5.87-66.7). Conclusions: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants