Expression of the endocannabinoid system and response to cannabinoid components by the human fetal testis.

BACKGROUND: Cannabis consumption by pregnant women continues to increase worldwide, raising concerns about adverse effects on fetal growth and deleterious impacts on the newborn, in connection with evidence of placental transfer of cannabis compound. Cannabis action is mediated by the endocannabinoid system (ECS), which expression is well established in the brain but unknown in the developing testis. The fetal testis, whose endocrine function orchestrates the masculinization of many distant organs, is particularly sensitive to disruption by xenobiotics. In this context, we aimed to determine whether cannabis exposure has the potential to directly impact the human fetal testis. METHODS: We determined the expression of components of the ECS in the human fetal testis from 6 to 17 developmental weeks and assessed the direct effects of phytocannabinoids Δ9-trans-tetrahydrocannabinol (THC) and cannabidiol (CBD) on the testis morphology and cell functions ex vivo. RESULTS: We demonstrate the presence in the human fetal testis of two key endocannabinoids, 2-arachidonylglycerol (2-AG) and to a lower level anandamide (AEA), as well as a range of enzymes and receptors for the ECS. Ex vivo exposure of first trimester testes to CBD, THC, or CBD/THC [ratio 1:1] at 10-7 to 10-5 M altered testosterone secretion by Leydig cells, AMH secretion by Sertoli cells, and impacted testicular cell proliferation and viability as early as 72 h post-exposure. Transcriptomic analysis on 72 h-exposed fetal testis explants revealed 187 differentially expressed genes (DEGs), including genes involved in steroid synthesis and toxic substance response. Depending on the molecules and testis age, highly deleterious effects of phytocannabinoid exposure were observed on testis tissue after 14 days, including Sertoli and germ cell death. CONCLUSIONS: Our study is the first to evidence the presence of the ECS in the human fetal testis and to highlight the potential adverse effect of cannabis consumption by pregnant women onto the development of the male gonad.

Prognostic significance of central venous-to-arterial carbon dioxide difference during the first 24 hours of septic shock in patients with and without impaired cardiac function.

OBJECTIVE: To investigate the prognostic significance of central venous-to-arterial carbon dioxide difference (cv-art CO 2 gap) during septic shock in patients with and without impaired cardiac function. METHODS: We performed a prospective cohort study in 10 French intensive care units. Patients suffering from septic shock were assigned to the impaired cardiac function group ('cardiac group', n =123) if they had atrial fibrillation (AF) and/or left ventricular ejection fraction (LVEF) <50% at study entry and to the non-cardiac group ( n =240) otherwise. RESULTS: Central venous and arterial blood gases were sampled every 6 h during the first 24 h to calculate cv-art CO 2 gap. Patients in the cardiac group had a higher cv-art CO 2 gap [at study entry and 6 and 12 h (all P <0.02)] than the non-cardiac group. Patients in the cardiac group with a cv-art CO 2 gap >0.9 kPa at 12 h had a higher risk of day 28 mortality (hazard ratio=3.18; P =0.0049). Among the 59 patients in the cardiac group with mean arterial pressure (MAP) ≥65 mm Hg, central venous pressure (CVP) ≥8 mm Hg and central venous oxygen saturation (ScvO 2 ) ≥70% at 12 h, those with a high cv-art CO 2 gap (>0.9 kPa; n =19) had a higher day 28 mortality (37% vs. 13%; P =0.042). In the non-cardiac group, a high cv-art CO 2 gap was not linked to a higher risk of day 28 death, whatever the threshold value of the cv-art CO 2 gap. CONCLUSION: Patients with septic shock and with AF and/or low LVEF were more prone to a persistent high cv-art CO 2 gap, even when initial resuscitation succeeded in normalizing MAP, CVP, and ScvO 2 . In these patients, a persistent high cv-art CO 2 gap at 12 h was significantly associated with higher day 28 mortality.

Diagnostic accuracy of urinary dipstick to exclude catheter-associated urinary tract infection in ICU patients: a reappraisal.

OBJECTIVES: We wanted to assess the diagnostic accuracy of urinary dipstick testing in excluding catheter-associated urinary tract infection (CAUTI) in intensive care unit (ICU) patients with fever or hypothermia. METHODS: This was a prospective observational cohort study in a medical-surgical ICU. Patients with new-onset fever >38.3 °C or hypothermia <36 °C at least 48 h after urinary catheter insertion were included over a 2-year period. At each episode, a urinary dipstick test and a urine culture were performed as the criterion standard. Extensive microbiological investigations for extra-urinary infections were performed also. The performances of various urinary dipstick result combinations in ruling out CAUTI were compared based on the likelihood ratios (LR+ and LR-). RESULTS: Symptomatic CAUTI was diagnosed in 31 (24.4 %) of the 127 included patients (195 episodes of fever or hypothermia). LR+ was best for combined leukocyte esterase-positive and nitrite-positive dipstick results (overall population: 14.91; 95 % confidence interval [95 % CI], 5.53-40.19; patients without urinary symptoms: 15.63; 95 % CI, 5.76-42.39). LR- was best for either leukocyte esterase-positive or nitrite-positive dipstick results (overall population: 0.41; 95 % CI, 0.57-0.65; patients without urinary symptoms, 0.36; 95 % CI, 0.21-0.60). CONCLUSIONS: Urinary dipstick testing at the bedside does not help to rule out symptomatic CAUTI in medical or surgical ICU patients with fever or hypothermia.