French Foundation Centre

Introduction: Acute hepatic porphyria (AHP) is caused by defects in hepatic heme biosynthesis leading to accumulation of the neurotoxic heme intermediates 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). Intravenous (IV) hemin, the recommended treatment for an acute attack, can have side effects. Givosiran reduced ALA and PBG levels, annualized attack rate (AAR; by 73%), hemin usage, and daily pain versus placebo in the 6-month, double-blind (DB) period of the ENVISION study (NCT03338816). Continued givosiran in the open-label extension (OLE) led to sustained clinical benefit, with 85% of patients attack free at months >15–18. Here we report data from the 24-month interim analysis of ENVISION. Methods: Patients with AHP (≥12 years old) with ≥2 attacks requiring hospitalization, urgent care, or IV hemin at home in the previous 6 months were randomized (1:1) to monthly subcutaneous givosiran 2.5 mg/kg (N = 48) or placebo (N = 46) for 6 months; 93 patients subsequently received givosiran 2.5 or 1.25 mg/kg in the OLE. Analysis included urinary ALA and PBG levels and annualized days of hemin use. QOL was assessed by 12-item Short Form Health Survey (SF-12), EuroQOL visual analog scale (EQ-VAS), and Porphyria Patient Experience Questionnaire (PPEQ). Results: During the OLE, givosiran led to a sustained lowering of median urinary ALA and PBG to near-normal levels in the continuous givosiran group and a >75% sustained reduction in the placebo crossover group. Continued givosiran treatment also led to a sustained reduction in attacks and hemin use in both groups (Table 1). Proportion of patients with zero attacks per 3-month interval improved over the OLE, with 83% of the continuous givosiran group attack free at months >21–24. Overall, 68% of patients did not require hemin during the OLE. Patients experienced further improvements in QOL and activities of daily living during the OLE versus the DB period, as assessed by SF-12 Physical Component Summary (Table 1), EQ-VAS, and PPEQ. Adverse events (AEs) included injection-site reactions and elevations of serum aminotransferases. Three patients (3.2%) discontinued treatment due to AEs. Conclusion: The ENVISION 24-month interim analysis further confirms that long-term givosiran provides sustained and continuous benefit to patients with AHP, maintaining reduced frequency of attacks and hemin use, and further improving QOL. The safety profile of givosiran remained acceptable and consistent with that previously observed.Table 1.: Efficacy of Long-term Givosiran in the Continuous Givosiran Group and Placebo Crossover Group in the DB and OLE Periods of the ENVISION. trial. AAR, annualized attack rate; DB, double-blind; OLE, open-label extension, SF-12, 12-item Short Form Health Survey.

The purpose of this study is to evaluate the feasibility of volume NT™, a new technique that automatically archives mid-sagittal plane views and measures the maximum NT (Nuchal Translucency) distance, by comparing NT measurements with the conventional two (2D) and three dimensional (3D) techniques. The study population consisted of 100 consecutive singleton undergoing NT screening at 11–13+6 weeks gestation. Fetuses with enlarged NT and multiple anomalies were excluded. Volume NT™, 2D and 3D techniques were performed with Accuvix V20 Prestige (Samsung Medison Co). Four experienced operators participated in this study. Each operator manually measured the NT according to Herman score, FMF (Fetal Medecine Foundation) and with in to in assessment. Then through an approximated mid-sagittal section determined by conventional B-mode ultrasound, the operator obtained an NT automatically using Volume NT™ software. One less experienced operator blinded to 2D and 3D measurements of experts examined archive images of patients and obtained automatic measurement of the NT with Volume NT™ from in to in of the two echogenic lines delineating the NT. Among the 100 cases initially included in this study, 24 cases were excluded from analysis because of exclusion criteria (NT increased and multiple abnormalities n = 6) or missing data (n = 18). Median measure of 2D NT (1.3 mm (0.7 to 3.4)) was higher than in 3D (1.2 mm (0.6 to 3)) without significant difference, probably due to “In to In” assessment. 25 cases of 2D NT measurements were associated with a low Herman score (<6). 23 of these 25 cases were associated with better Herman score (≥6) using Volume NT and even those measured by the least experienced operator (p = 0.035). Volume NTTM helps to improve Herman score, whenever 2D NT assessment is difficult to get, by obtaining a better sagittal plane, even in the hands of a less experienced operator.

Sexual differentiation of the external and internal genitalia depends on a complex process and involves several physiopathological mechanism. Primitive gonad will differentiate under the SRY effect in testis that will secrete testosterone and AMH causing regression of Müllerian ducts, persistence of Wolffian ducts and virilisation. In the absence of SRY, primitive gonad differentiate into ovaries, with regression of Wolffian ducts and persistence of Müllerian ducts responsible of uterus, salpinx and the third superior part of vagina. The external genitalia are female. The unusual aspect of the external genitalia is found in many pathology but also in Congenital Adrenal Hyperplasia (CAH) and Partial Androgen Insensitivity Syndrome (PAIS). A new exploration technique of internal genitalia and particularly the visualisation of the existence of a fetal uterus help to differentiate these two pathologies. An acoustic window through the proximal femoral epiphysis allows viewing the cervix when present. Supporting information can be found in the online version of this abstract Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.