Reesevelling2454

However, remarkable progress has been achieved with the identification of novel potent and selective RET kinase inhibitors for the treatment of advanced thyroid cancer. Although expanded clinical validation in future trials is needed, the sustained antitumoural activity and the improved safety profile of these novel compounds is opening a new exciting era in precision oncology for RET-driven cancers.

Morphine is commonly used for postoperative analgesia in children. Here we studied the pharmacodynamics of morphine in children after cardiac surgery receiving protocolized morphine.

Data on morphine rescue requirements guided by validated pain scores in children (n = 35, 3-36 months) after cardiac surgery receiving morphine as loading dose (100 μg kg

) with continuous infusion (40 μg kg

 h

) from a previous study on morphine pharmacokinetics were analysed using repeated time-to-event (RTTE) modelling.

During the postoperative period (38 h (IQR 23-46)), 130 morphine rescue events (4 (IQR 1-5) per patient) mainly occurred in the first 24 h (107/130) at a median morphine concentration of 29.5 ng ml

(range 7-180 ng ml

). In the RTTE model, the hazard of rescue morphine decreased over time (half-life 18 h; P < 0.001), while the hazard for rescue morphine (21.9% at 29.5 ng ml

) increased at higher morphine concentrations (P < 0.001).

In this study on protocolized morphine analgesia in childrenne rescue events were identified at a wide range of morphine concentrations upon a standardized pain protocol consisting of continuous morphine infusion and morphine as rescue boluses. The expected number of rescue morphine events was found to increase at higher morphine concentrations. Instead of exploring more aggressive morphine dosing, future research should focus on a multimodal approach to treat breakthrough pain in children.

The brain of chronically ventilated preterm human infants is vulnerable to collateral damage during invasive mechanical ventilation (IMV). Damage is manifest, in part, by learning and memory impairments, which are hippocampal functions. A molecular regulator of hippocampal development is insulin-like growth factor 1 (IGF1). A gentler ventilation strategy is noninvasive respiratory support (NRS). We tested the hypotheses that NRS leads to greater levels of IGF1 messenger RNA (mRNA) variants and distinct epigenetic profile along the IGF1 gene locus in the hippocampus compared to IMV.

Preterm lambs were managed by NRS or IMV for 3 or 21 days. Isolated hippocampi were analyzed for IGF1 mRNA levels and splice variants for promoter 1 (P1), P2, and IGF1A and 1B, DNA methylation in P1 region, and histone covalent modifications along the gene locus.

NRS had significantly greater levels of IGF1 P1 (predominant transcript), and 1A and 1B mRNA variants compared to IMV at 3 or 21 days. NRS also led to more DNA methyl outcomes later in life versus IMV. Also, duration of IMV is directly related to hippocampal damage; however, molecular players remain unknown. NRS, as a gentler mode of respiratory management of preterm neonates, may reduce damage to the immature hippocampus through an epigenetic mechanism.

Dead space is the volume not taking part in gas exchange and, if increased, could affect alveolar ventilation if there is too low a delivered volume. We determined if there were differences in dead space and alveolar ventilation in ventilated infants with pulmonary disease or no respiratory morbidity.

A prospective study of mechanically ventilated infants was undertaken. Expiratory tidal volume and carbon dioxide levels were measured. Volumetric capnograms were constructed to calculate the dead space using the modified Bohr-Enghoff equation. Alveolar ventilation (V

) was also calculated.

Eighty-one infants with a median (range) gestational age of 28.7 (22.4-41.9) weeks were recruited. The dead space [median (IQR)] was higher in 35 infants with respiratory distress syndrome (RDS) [5.7 (5.1-7.0) ml/kg] and in 26 infants with bronchopulmonary dysplasia (BPD) [6.4 (5.1-7.5) ml/kg] than in 20 term controls with no respiratory disease [3.5 (2.8-4.2) ml/kg, p < 0.001]. Minute ventilation was higher in bothlated infants with respiratory distress syndrome or evolving bronchopulmonary dysplasia compared to term controls without respiratory disease. The dead space volume should be considered when calculating the most appropriate volume during volume-targeted ventilation.

Torsion of the testis is an urgent surgical condition that endangers the viability of the gonad and the fertility of the patient. Our aim was to assess potential autoimmune processes and hormonal abnormalities in boys operated on due to that illness.

The authors evaluated the levels of antibodies against sperm and Leydig cells, concentrations of follicle-stimulating, luteinizing and anti-Müllerian hormone, testosterone, oestradiol and vascular endothelial growth factor in the serum in 28 boys operated on due to torsion of the testis. Patients' sexual maturity was assessed according the Tanner scale (group G1, G4 and G5).

No antibodies against sperm or Leydig cells were found in the serum. Statistically significant differences in follicle-stimulating and anti-Müllerian hormone concentrations were observed in the G1, and they were higher in the study than in the control group. There were no statistically significant differences in luteinizing hormone, testosterone, oestradiol and vascular endothelial growe formation of antibodies and hormonal changes due to testicular torsion in boys. It is a novel, prospective study on antibodies against sperms and Leydig cells in the serum and on hormonal processes occurring as a result of the testicular torsion from the prenatal period to the adolescence with division into pubertal groups. The study has revealed sufficient compensation capabilities of the pituitary-testis axis and no autoimmune process in boys with torsion of the testis.

A reduced lung function in early adulthood is associated with respiratory and non-respiratory diseases and is a long-term predictor of mortality. This study investigated the association between early socioeconomic circumstances (SEC) and lung function growth trajectories from early adolescence until early adulthood.

We analysed data from the EPITeen population-based study, including adolescents born in 1990. Study waves occurred at 13, 17 and 21 yearsof age. Information on sociodemographic, behavioural and health factors, anthropometry and spirometry was collected. Early-life SEC were assessed using maternal education and paternal occupational position. The forced expiratory volume in the first second (FEV

) growth trajectories were drawn considering sex-and-height interactions over an 8-year period. OTS514 mouse Our sample included 2022 participants with complete informationfor the relevant variables.

Participants from most disadvantaged SEC presented lower FEV

at early adolescence compared to high-SEC counterparts, but differences seem to diminish with height growth.