Incidental findings in a series of 2500 gene panel tests for a genetic predisposition to cancer: Results and impact on patients.

With next generation sequencing, physicians are faced with more complex and uncertain data, particularly incidental findings (IF). Guidelines for the return of IF have been published by learned societies. However, little is known about how patients are affected by these results in a context of oncogenetic testing. Over 4 years, 2500 patients with an indication for genetic testing underwent a gene cancer panel. If an IF was detected, patients were contacted by a physician/genetic counsellor and invited to take part in a semi-structured interview to assess their understanding of the result, the change in medical care, the psychological impact, and the transmission of results to the family. Fourteen patients (0.56%) were delivered an IF in a cancer predisposition gene (RAD51C, PMS2, SDHC, RET, BRCA2, CHEK2, CDKN2A, CDH1, SUFU). Two patients did not collect the results and another two died before the return of results. Within the 10 patients recontacted, most of them reported surprise at the delivery of IF, but not anxiety. The majority felt they had chosen to obtain the result and enough information to understand it. They all initiated the recommended follow-up and did not regret the procedure. Information regarding the IF was transmitted to their offspring but siblings or second-degree relatives were not consistently informed. No major adverse psychological events were found in our experience. IF will be inherent to the development of sequencing, even for restricted gene panels, so it is important to increase our knowledge on the impact of such results in different contexts.

Risk factors of postoperative vomiting in children receiving continuous intravenous morphine.

BACKGROUND: Risk factors of postoperative vomiting (POV) have been less extensively explored in children compared to adults. We analyzed the risk factors of POV in children receiving continuous intravenous (i.v.) morphine in a standardized manner without POV prophylaxis after major surgery. METHODS: This observational retrospective study included 235 children aged from 2 to 216 months (91 F:144 M, 11.5% <6 months, 31.5% 6-11 months). The primary end point was the occurrence of at least one episode of POV recorded on the nursing chart. The independent predictors of POV were determined by univariate analysis followed by a multivariate analysis by logistic regression. The data are presented as either medians (25th-75th percentile) or as values with a 95% confidence interval. RESULTS: Continuous i.v. morphine was administered over 42 (22-60) h with an initial infusion rate of 20 µg x kg(-1) x h(-1) in 63% of cases, which was increased in 31.5% of cases and was accompanied by an additional bolus in 39.2% of children. At least one episode of POV occurred in 22.6% of children. The following three independent factors were associated with POV: female gender (OR 3.324 [1.695-6.519], P=0.0005), urological surgery (OR 5.605 [1.291-24.340], P=0.0214) and age (OR 1.012 [1.006-1.018], P<0.0001). The discriminating characteristics of the model were good with an ROC curve AUC of 0.778, sensitivity of 71.7% and specificity of 71.4% for a 0.22 cut-off value of POV incidence. The positive predictive value was 42.2%, and the negative predictive value was 89.6%. CONCLUSION: Female gender, which is usually considered a risk factor after puberty, should be taken into account independent of age to guide the POV prophylaxis in children receiving a postoperative continuous i.v. morphine infusion.

Islet-cell-to-cell communication as basis for normal insulin secretion.

The emergence of pancreatic islets has necessitated the development of a signalling system for the intra- and inter-islet coordination of beta cells. With evolution, this system has evolved into a complex regulatory network of partially cross-talking pathways, whereby individual cells sense the state of activity of their neighbours and, accordingly, regulate their own level of functioning. A consistent feature of this network in vertebrates is the expression of connexin (Cx)-36-made cell-to-cell channels, which cluster at gap junction domains of the cell membrane, and which adjacent beta cells use to share cytoplasmic ions and small metabolites within individual islets. This chapter reviews what is known about Cx36, and the mechanism whereby this beta-cell connexin significantly regulates insulin secretion. It further outlines other less established functions of the protein and evaluates its potential relevance for the development of novel therapeutic approaches to diabetes.

Premedication with midazolam in children. Effect of intranasal, rectal and oral routes on plasma midazolam concentrations.

We report a study performed to compare the time and plasma drug concentrations necessary to achieve a similar state of sedation after midazolam premedication given by various routes in children of 2-5 years old. Children were randomly allocated to one of three groups to receive midazolam 0.2 mg.kg-1 given intranasally, 0.5 mg.kg-1 given orally or 0.3 mg.kg-1 given rectally. Sedation was measured regularly until venepuncture was possible in a cooperative child. At this time, a first blood sample was taken to measure plasma concentration, followed by another 10 min later. Anaesthesia consisted of intravenous propofol supplemented with regional analgesia. At recovery from anaesthesia, a third blood sample was taken. Adequate sedation occurred sooner (7.7, SD 2.4 min) with intranasal than oral (12.5, SD 4.9 min) or rectal (16.3, SD 4.2 min) midazolam. The initial blood levels were lower when the drug was given by the alimentary routes despite higher doses (146, SD 51 ng.ml-1 in 11.5, SD 3.9 min; 104, SD 34 ng.ml-1 in 21 +/- 6 min; and 93, SD 63 ng.ml-1 in 23.1, SD 3.5 min for the intra nasal, rectal and oral routes respectively). Duration of surgical procedures, and of propofol infusion, and recovery from anaesthesia was similar for the three groups. The only problem arose in a 30-month-old boy in the intranasal group who developed respiratory depression with a plasma midazolam concentration of 169 ng.ml-1. Intranasal midazolam is an excellent alternative for rapid premedication provided that respiratory monitoring is used.

An armoured endotracheal tube obstruction in a child.

The case of a child whose tracheal tube became obstructed intraoperatively 30 minutes after intubation is reported. It appears that this obstruction was related to the development of bubbles within the walls which expanded upon exposure to nitrous oxide and diffusion of that gas into the bubbles. The authors want to point out the risk of gas diffusion into the walls of the tube and the possibility that repeated sterilization may enhance the development of bubbles.

[Halogenated inhalation anesthesia with a semiclosed circle system]. / Anesthésie halogénée utilisant un respirateur muni d'un circuit-filtre.

Thirty-six patients were anaesthetized for a maxillofacial surgical procedure. Ventilation was controlled by a ventilator (Kontron ABT 4100) with a semi-closed circle system. The flow of fresh gases was 1,200 ml.min-1. The vaporizer for the halogenated anaesthetic agent was placed out of the circle before the ventilator. Halothane was used for maintenance of anaesthesia and isoflurane for induced hypotension in orthognathic surgery. The inspired concentration of the halogenated agent was monitored by an analyser. A linear correlation between the delivered and the inhaled concentration of halogenated agent was established, the latter never reaching the delivered concentration. Monitoring the inspired oxygen concentration was required, so as to maintain a constant value. Carbon dioxide absorption by soda lime was also studied. The known advantages were: substantial economies in nitrous oxide and halogenated agents, prevention of contamination of the operating theatre, humidification and warning of the inspired gases. The use of such a system with the vaporizer out of the circle was safe, all the more so as the concentration of inhaled halogenated agents could be predicted.

[An original intubation technic in a child with Pierre Robin syndrome]. / Technique originale d'intubation chez un enfant porteur d'un syndrome de Pierre Robin.

Infants with Pierre Robin syndrome often present the anaesthesiologist with the challenge of upper airway obstruction and difficult tracheal intubation. An unconventional method for solving this problem was used in a 2 week old 2.2 kg term male infant who presented with severe micrognathia, a widely cleft palate and extreme glossoptosis. Hyperextension of the head in the prone position distracted the epiglottis from the glottis. Blind nasotracheal intubation was then used. The curve of the nasotracheal tube made it pass behind the epiglottis into the larynx.

[Anesthetic aspects of the primary treatment of labio-maxillo-palatal clefts]. / Aspects anesthésiques du traitement primaire des fentes labio-maxillo-palatines.

This study of 97 operations discusses our anaesthetic experience for labio-maxillary clefts and the problems which arise for the anaesthetist during pre-inter and post surgical periods. This type of functional surgery is carried out on children between 4 and 23 months old, of which 22% presented with associated malformations. Paediatric anaesthetic characteristics in a maxillo-facial context are discussed in detail. We indicate the importance of installing the different surveillance elements before placement of the surgical fields. We treat the problems of drug interactions between the halogenic anaesthetics and vasoconstrictor used for local haemostasis, the limits of spontaneous ventilation and the secondary metabolic consequences of prolonged fasting.

[Use of ventilation by oxygen injection in laryngeal microsurgery]. / Utilisation de la ventilation par injection d'oxygène au cours de la microchirurgie laryngée

Thirty patients with a laryngeal polyp or other tumour, were operated on under the microscope. During the operation, which lasted from 10 to 30 minutes, ventilation was ensured by injection of oxygen at 3 to 4 atmospheric pressures through a naso-tracheal catheter. Anaesthesia was obtained by an association of propanidide, small doses of analgesic and succinycholine, constant rate syringes were used for maintenance of narcosis and curarisation. In 23 patients, blood gases were analysed at various stages of the operation permitting one to assess the quality of the ventilation carried out. In a few patients, it was also possible to record pressure curves in the trachea. The results were excellent, both concerning the quality of the ventilation and that of the anaesthesia together with the operative conditions. After recalling the main characteristics of this mode of ventilation which uses Venturi's principle, the authors expose the other methods which are variants compared with their technique of use of this procedure for laryngeal micro-surgery.