La mise en place du peau à peau dans l’unité de néonatologie en maternité (UNM) : représentations parentales et professionnelles

International audienc

Automated synthesis of [18F]DCFPyL via direct radiofluorination and validation in preclinical prostate cancer models

Background: Prostate-specific membrane antigen (PSMA) is frequently overexpressed and upregulated in prostate cancer. To date, various 18F- and 68Ga-labeled urea-based radiotracers for PET imaging of PSMA have been developed and entered clinical trials. Here, we describe an automated synthesis of [18F]DCFPyL via direct radiofluorination and validation in preclinical models of prostate cancer. Methods: [18F]DCFPyL was synthesized via direct nucleophilic heteroaromatic substitution reaction in a single reactor TRACERlab FXFN automated synthesis unit. Radiopharmacological evaluation of [18F]DCFPyL involved internalization experiments, dynamic PET imaging in LNCaP (PSMA+) and PC3 (PSMA−) tumor-bearing BALB/c nude mice, biodistribution studies, and metabolic profiling. In addition, reversible two-tissue compartmental model analysis was used to quantify pharmacokinetics of [18F]DCFPyL in LNCaP and PC3 tumor models. Results: Automated radiosynthesis afforded radiotracer [18F]DCFPyL in decay-corrected radiochemical yields of 23 ± 5 % (n = 10) within 55 min, including HPLC purification. Dynamic PET analysis revealed rapid and high uptake of radioactivity (SUV5min 0.95) in LNCaP tumors which increased over time (SUV60min 1.1). Radioactivity uptake in LNCaP tumors was blocked in the presence of nonradioactive DCFPyL (SUV60min 0.22). The muscle as reference tissue showed rapid and continuous clearance over time (SUV60min 0.06). Fast blood clearance of radioactivity resulted in tumor-blood ratios of 1.0 after 10 min and 8.3 after 60 min. PC3 tumors also showed continuous clearance of radioactivity over time (SUV60min 0.11). Kinetic analysis of PET data revealed the two-tissue compartmental model as best fit with K 1 = 0.12, k 2 = 0.18, k 3 = 0.08, and k 4 = 0.004 min−1, confirming molecular trapping of [18F]DCFPyL in PSMA+ LNCaP cells. Conclusions: [18F]DCFPyL can be prepared for clinical applications simply and in good radiochemical yields via a direct radiofluorination synthesis route in a single reactor automated synthesis unit. Radiopharmacological evaluation of [18F]DCFPyL confirmed high PSMA-mediated tumor uptake combined with superior clearance parameters. Compartmental model analysis points to a two-step molecular trapping mechanism based on PSMA binding and subsequent internalization leading to retention of radioactivity in PSMA+ LNCaP tumors.Medicine, Faculty ofNon UBCRadiology, Department ofReviewedFacult

Dynamics of the digestive acquisition of bacterial carriage and integron presence by French preterm newborns according to maternal colonization: The DAIR3N multicentric study

ObjectivesThe study aimed to describe the dynamics and risk factors of Gram-negative bacteria (GNB) acquisition in preterm infants.MethodsThis prospective multicenter French study included mothers hospitalized for preterm delivery and their newborns, followed until hospital discharge. Maternal feces and vaginal fluids at delivery, and neonatal feces from birth to discharge were tested for cultivable GNB, potential acquired resistance, and integrons. The primary outcome was the acquisition of GNB and integrons in neonatal feces, and their dynamics, evaluated by survival analysis using the actuarial method. Risk factors were analyzed using Cox models.ResultsTwo hundred thirty-eight evaluable preterm dyads were included by five different centers over 16 months. GNB were isolated in 32.6% of vaginal samples, with 15.4% of strains producing extended-spectrum beta-lactamase (ESBL) or hyperproducing cephalosporinase (HCase), and in 96.2% of maternal feces, with 7.8% ESBL-GNB or HCase-GNB. Integrons were detected in 40.2% of feces and 10.6% of GNB strains. The mean (SD) length of stay of newborns was 39.5 (15.9) days; 4 died in the hospital. At least one infection episode occurred in 36.1% of newborns. The acquisition of GNB and integrons was progressive from birth to discharge. At discharge, half of newborns had ESBL-GNB or HCase-GNB, independently favored by a premature rupture of membranes (Hazard Ratio (HR), 3.41, 95% confidence interval (CI), 1.71; 6.81), and 25.6% had integrons (protective factor: multiple gestation, HR, 0.367, 95% CI, 0.195; 0.693).ConclusionIn preterm newborns, the acquisitions of GNB, including resistant ones, and integrons are progressive from birth to discharge. A premature rupture of membranes favored the colonization by ESBL-GNB or Hcase-GNB

Clinical value of serial quantitative analysis of cytomegalovirus DNA in blood and saliva over the first 24 months of life congenital infection: the French Cymepedia Cohort

International audienceObjective: To evaluate cytomegalovirus (CMV) viral load dynamics in blood and saliva during the first two years of life in symptomatic and asymptomatic infected infants and to identify whether these kinetics could have practical clinical implications.Study design: The Cymepedia cohort prospectively included 256 congenitally infected neonates followed for two years. Whole blood and saliva were collected at inclusion, months 4 and 12, and saliva at months 18 and 24. Real-time CMV PCR was performed, results expressed as log10 IU/mL in blood and in copies/mL in saliva.Results: Viral load in saliva progressively decreased from 7.5 log10 at birth to 3.3 log10 at month 24. CMV PCR in saliva was positive in 100% and 96% of infants at 6 and 12 months, respectively. In the first month of life, neonatal saliva viral load <5 log10 was related to a late CMV transplacental passage. Detection in blood was positive in 92% (147/159) of neonates in the first month of life. No viral load threshold values in blood or saliva could be associated with a high risk of sequelae. Neonatal blood viral load <3 log10 IU/ml had a 100% negative predictive value (NPV) for long-term sequelae.Conclusions: Viral loads in blood and saliva by CMV PCR testing in congenital infection fall over the first 24 months. In this study of infants affected mainly after primary maternal infection during pregnancy, all salivary samples were positive in the first 6 months of life and sequelae were not seen in infants with neonatal blood viral load <3 log10 IU/mL