Vulvar and vaginal melanomas: A retrospective study spanning 19 years from a tertiary center.

INTRODUCTION: Mucosal melanomas (MM) of the female genital tract are rare a. We aimed to study the prognostic factors of vulvar and vaginal locations of MM. MATERIAL AND METHOD: A multicenter, retrospective cohort study conducted between 01/01/2000 and 01/06/2019. RESULT: Of the 33 patients included 25 (75.8 %) had vulvar (VuM) and eight (24.2 %) vaginal melanomas (VaM). VaMs were deeper: median Breslow index: 17.5mm [3.5-22] versus 4.3mm [0.35-18] (p=0.013). Average follow-up was 24.0±59.8 months. Twenty-six patients (78.8 %) experienced recurrence. Disease-free survival was 52.9 % at 1year (64.7 % for VuM and 14.3 % for VaM) and 8.4 % at 3 years (11 % for VuM and 0% for VaM) (p=0.002). Median time to the first recurrence was 9.01 months [CI95 %: 2.07-56.71]. VaM recurred earlier than VuM (3.12 months [CI95 %: 2.07-12.49] versus 17.72 [CI95 %: 3.58-56.71], p=0.011). VaM had a higher risk of recurrence (HR=5.64 [CI95 %: 2.01-15.82], p=0.001) in multivariate analysis. Overall survival was 88.5 % at 1year (100 % for VuM and 50 % for VaM), and 59.4 % at 3 years (69.3 % for VuM and 25 % for VaM). Women with VaM died earlier: median specific death occurrence of 8.76 months [CI95 %: 6.54-24.72] versus 39.61 [CI95 %: 21.89-209.21], p=0.013 (HR=5.08 [CI95 %: 1.39-18.60], p=0.014). A lesion size ≥3cm was associated with an increased risk of mortality (HR=8.45 [CI95 %: 1.60-44.52], p=0.012). In multivariate analysis, vaginal location remained an independent and predictive variable of a higher risk of specific death (HR=8.56 [CI95 %: 1.95-37.64], p=0.005). CONCLUSION: A vaginal location of MM is associated with a poorer prognosis than a vulvar location.

Teriflunomide-exposed pregnancies in a French cohort of patients with multiple sclerosis.

OBJECTIVE: To describe pregnancies exposed to teriflunomide (TERIF) in women with multiple sclerosis (MS) in France over the period 2014-2016. METHODS: All 15- to 49-year-old women with MS in the national health insurance database were included. Pregnancies that had started between August 2014 and March 2016 were identified from their outcomes. Three groups according to treatment exposure were compared: TERIF, interferons (IFNs) or glatiramer acetate, and no medication. RESULTS: Among the 44,008 women with MS followed 24.5 months on average, 2,639 pregnancies were identified. There were 1,538 pregnancies (58.3%) that were not exposed to any MS treatment in accordance with the guidelines. A total of 673 pregnancies (25.5%) were exposed to IFN and/or glatiramer acetate, and possible or probable exposure to contra-indicated treatments was observed in 428 pregnancies (16.2%), of whom 47 pregnancies were exposed to TERIF. The annual incidence rate of pregnancies exposed to TERIF was 1.4 per 100 patient-years; i.e., 3 times less than the 2 control groups (5.6 and 4.7, respectively). The median exposure duration to TERIF was 45 days after conception. The outcomes comprised 23 live births, 22 abortions (3 times more than the 2 other groups), and 2 miscarriages. All newborns were healthy at birth. CONCLUSIONS: Despite specific TERIF guidelines for pregnancy-related issues and the availability of alternative therapies, some pregnancies exposed to TERIF were identified. Most of the cases were because of the absence of the recommended accelerated elimination procedure and appeared to be mostly unplanned pregnancies that probably reflect a lack of effective contraception.

Prenatal exposure to glycol ethers and response inhibition in 6-year-old children: The PELAGIE cohort study.

BACKGROUND: Exposure to glycol ethers (GEs) is suspected of impairing neurodevelopment in children, but the specific impact on their inhibitory capacity, a central deficit of ADHD, has never been studied. We aimed to assess the impact of prenatal exposure to GEs on the response inhibition of children aged six years. METHODS: In total, 169 mother-child pairs from the French cohort PELAGIE (2002-2006) were studied. Maternal urinary concentrations of six GE metabolites (alkoxycarboxylic acids) were measured during pregnancy. Multiple imputation by quantile regression was used to handle non-detected values and the data were then classified into quartiles. Inhibition of children was evaluated by the Rhythmic Continuous Performance Test 90 (R-CPT90). The inhibition score (percentage of correct responses to non-target stimuli) was corrected for compliance with the instructions (percentage of correct responses to target stimuli). The analysis used a multiple linear regression model, adjusting for confounding factors for each metabolite. RESULTS: Median concentrations of metabolites ranged from 0.02 mg/L (Ethoxyacetic acid, EAA) to 0.39 mg/L (Phenoxyacetic acid, PhAA). The median corrected inhibition score was 37.9% [first quartile: 29.8 - third quartile: 47.9]. We found a negative and statistically significant association between the inhibition score and prenatal urinary EAA concentration (p-trend = 0.03), with a significant ß coefficient for the third quartile (ß = -0.064; 95% confidence interval: -0.121, -0.007). There were no statistically significant associations for the other five metabolites. CONCLUSION: These results are consistent with the hypothesis of possible impact of prenatal environmental exposure on inhibitory capacity among children. Data about the GEs metabolized to EAA (history of exposure sources and toxicokinetics) should be gathered to further interpret these results and guide precautionary measures.