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

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, 5.1–6.5). 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 co-morbidities, 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

The Model of the Optimal Number of Public Transport Vehicles in Mixed Traffic Flow Conditions: A Case Study

Bus passenger transport is very important for sustainable urban mobility, and due to the characteristics of the street network, it is usually realized in the conditions of mixed traffic flow. Disturbances and sudden changes of traffic flow parameters occurring in the street network in a mixed traffic flow affect the disruptions in schedule and travel time of all vehicles in the traffic flow, including public transport (PT) vehicles. In order to keep to the planned schedule in the peak hours of PT lines carried out in the conditions of mixed traffic flow, the operators introduce new vehicles or reduce the vehicles’ dwell time at terminuses, which is often impossible to do. The use of a larger number of public transport vehicles increases the fuel consumption, pollutants’ emission, and the operating costs. In this paper, a network optimization model was developed for defining the influence of the change of traffic flow parameters in a mixed traffic flow on travel time of PT vehicles. The model takes into consideration uncertain time unevenness of the change of traffic flow parameters, which enables determining the optimization of travel time and defining the necessary number of public transport vehicles for the purpose of keeping to the planned schedule. In order to develop the transport model, counting and analysis of the characteristics of traffic flow at 61 intersections on the city territory were carried out. The model was tested on bus line number 4 of PT in Novi Sad. The model showed that it is possible to achieve certain savings regarding the number of vehicles with the unchanged headway, that is, the unchanged level of service which is offered to the users. With the application of the model in real traffic conditions, significant savings, as well as operating and external costs’ reduction, can be achieved, which contributes to the sustainability of public bus transport in urban environments

Biosynthetic Products from a Nearshore-Derived Gram-Negative Bacterium Enable Reassessment of the Kailuin Depsipeptides

Sampling of California nearshore sediments resulted in the isolation of a Gram-negative bacterium, <i>Photobacterium halotolerans</i>, capable of producing unusual biosynthetic products. Liquid culture in artificial seawater-based media provided cyclic depsipeptides including four known compounds, kailuins B–E (<b>2</b>–<b>5</b>), and two new analogues, kailuins G and H (<b>7</b> and <b>8</b>). The structures of the new and known compounds were confirmed through extensive spectroscopic and Marfey’s analyses. During the course of these studies, a correction was made to the previously reported double-bond geometry of kailuin D (<b>4</b>). Additionally, through the application of a combination of derivatization with Mosher’s reagent and extensive ¹³C NMR shift analysis, the previously unassigned chiral center at position C-3 of the β-acyloxy group of all compounds was determined. To evaluate bioactivity and structure–activity relationships, the kailuin core (<b>13</b>) and kailuin lactam (<b>14</b>) were prepared by chiral synthesis using an Fmoc solid-phase peptide strategy followed by solution-phase cyclization. All isolated compounds and synthetic cores were assayed for solid tumor cell cytotoxicity and showed only minimal activity, contrary to other published reports. Additional phenotypic screenings were done on <b>4</b> and <b>5</b>, with little evidence of activity