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. Clinical trial registration: NCT02350348

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among comorbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. Conclusions: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event. Clinical trial registration: NCT02350348

Enzymatic Preparation of 2 5 ,3 5 Cyclic Dinucleotides, Their Binding Properties to Stimulator of Interferon Genes Adaptor Protein, and Structure Activity Correlations

Cyclic dinucleotides are second messengers in the cyclic GMP AMP synthase cGAS stimulator of interferon genes STING pathway, which plays an important role in recognizing tumor cells and viral or bacterial infections. They bind to the STING adaptor protein and trigger expression of cytokines via TANK binding kinase 1 TBK1 interferon regulatory factor 3 IRF3 and inhibitor of nuclear factor amp; 954;B I amp; 954;B kinase IKK nuclear factor amp; 954;B NF amp; 954;B signaling cascades. In this work, we describe an enzymatic preparation of 2 amp; 8242; 5 amp; 8242;,3 amp; 8242; 5 amp; 8242; cyclic dinucleotides 2 amp; 8242;3 amp; 8242;CDNs with use of cyclic GMP AMP synthases cGAS from human, mouse, and chicken. We profile substrate specificity of these enzymes by employing a small library of nucleotide 5 amp; 8242; triphosphate NTP analogues and use them to prepare 33 2 amp; 8242;3 amp; 8242;CDNs. We also determine affinity of these CDNs to five different STING haplotypes in cell based and biochemical assays and describe properties needed for their optimal activity toward all STING haplotypes. Next, we study their effect on cytokine and chemokine induction by human peripheral blood mononuclear cells PBMCs and evaluate their cytotoxic effect on monocytes. Additionally, we report X ray crystal structures of two new CDNs bound to STING protein and discuss structure activity relationship by using quantum and molecular mechanical QM MM computational modelin

Produtividade da chicória (Cichorium endivia L.) em função de tipos de bandejas e idade de transplante de mudas Endive (Cichorium endivia L.) yield in function of tray types and seedlings age at transplanting

A chicória (Cichorium endivia L.) tem apresentado aumento crescente de cultivo no Brasil, constituindo-se atualmente numa hortaliça folhosa importante, consumida principalmente como salada. No entanto, ainda são escassas as informações existentes sobre a cultura. O objetivo desse experimento foi avaliar os efeitos de tipos de bandejas e idade de transplante de mudas na produtividade de chicória. As mudas foram produzidas sob ambiente protegido, com a cultivar AF-254 (SAKATA). O delineamento experimental foi o de blocos casualizados, com quatro repetições, sendo os tratamentos arranjados em esquema fatorial 4 x 3, sendo quatro idades de transplante de mudas (25, 30, 35 e 42 dias após a semeadura) e três tipos de bandejas, com 128, 200 e 288 células. O substrato usado foi o Plantmax®. As semeaduras foram realizadas entre os dias 11/04/05 a 28/04/05, com intervalo de sete dias da primeira semeadura e de cinco dias na segunda, terceira e quarta semeadura. O transplante foi efetuado no dia 23/05/04, em parcelas compostas de três fileiras de plantas arranjadas no espaçamento 0,30 x 0,30 m. A colheita foi realizada de acordo com a maturidade da planta. Mudas obtidas da bandeja de 128 células foram superiores independentemente da idade. As maiores diferenças encontradas foram entre as bandejas de 128 com as de 288 células. O ponto de máximo desenvolvimento das mudas nas características avaliadas foi entre 30 e 40 dias, nos três tipos de bandejas. A maior produtividade da chicória foi proveniente de mudas obtidas da bandeja de 128 células e as idades de 30 e de 35 dias. A alta produtividade obtida com a muda da bandeja de 128 células compensa o maior investimento na produção de mudas.<br>Endive (Cichorium endivia L.) production has increased in Brazil, where it is currently considered an important vegetable, being consumed mainly as salad. However, the studies about this crop are scarce. This work aimed to avaluate the effects of tray types and age of seedlings at transplanting on endive yield. Seedlings were produced under protected cultivation, with the cultivar AF-254 (SAKATA). The experimental design used was a randomized blocks, with four replications, and the treatments arranged in a factorial scheme 4x3, being four seedlings age at transplanting (25, 30, 35 and 42 days after sowing) and three tray types (with 128, 200 and 288 cells). The substrate used was Plantmax®. Seeds were sowed between the period of March, 11th to March, 28th, in 2005, with the intervals of seven days from the first to second sowing, and five days from each other. The seedlings were tranplanted in May, 23th, in plots with three rows and plants arranged in 0,30x0,30m. Plants were harvested as they reached maturation. Seedlings produced on tray of 128 cells were superior, independent of the age. The highest difference was observed when trays with 128 and 288 cells were compared. The highest point of seedlings development was observed between 30 and 40 days on the three tray types. The best option for endive production was obtained from seedlings produced on tray of 128 cells and with ages of 30 and 35 days. The high yield obtained with the seedlings from 128 trays repay the cost on seedlings production

Corrigendum to ‘Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study’ (Br J Anaesth 2021; 126: 1173–81) (British Journal of Anaesthesia (2021) 126(6) (1173–1181), (S0007091221001161), (10.1016/j.bja.2021.02.021))

The authors regret that errors were present in the above article. On page 1174, in the second paragraph of the Statistical methods section, the second sentence should read as follows: The incidence of difficult intubation was determined including those whose tracheas were already intubated and is reported as a percentage with a 95% exact binomial CI. On page 1175, in the third paragraph of the Statistical methods section ‘mean standardised difference (MSD)’ should read ‘standardised mean difference (SMD)’ The authors would like to apologise for any inconvenience caused