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Resume Objectifs En appui sur les donnees issues d’une vaste recherche medico-psychopathologique proposee a des jeunes filles atteintes d’une agenesie utero-vaginale — syndrome de Rokitansky ou Mayer-Rokitansky-Kuster-Hauser (MRKH) — notre travail propose l’analyse psychodynamique de la valeur et de la fonction pour l’economie psychosomatique d’une reaction frequente a l’annonce diagnostique : le developpement d’un desordre alimentaire de type prise de poids chez 4 patientes sur 40. La mise en perspective de l’analyse de deux cas de patientes permet d’affiner la comprehension du sens de cette emergence alimentaire dont nous faisons l’hypothese qu’elle constitue a la fois une modalite defensive signalant les impasses du processus de construction du feminin mais aussi possiblement un levier de transformation psychique de ses incidences traumatiques. Methode Quarante jeunes femmes MRKH âgees de 19 a 34 ans (avec un âge moyen de 25 ans ½) ont ete rencontrees. La recherche leur a ete proposee de 2 a 17 ans apres leur annonce diagnostique et le travail clinique a consiste en une analyse retrospective de leur experience traumatique adolescente. Le recit des patientes a ete recueilli a l’aide d’un entretien clinique a visee de recherche non directif. Deux epreuves projectives (Rorschach et Thematic Apperception Test – TAT) leur ont egalement ete proposees pour apprehender plus finement les modalites de leur fonctionnement psychique. Les donnees des entretiens font l’objet d’une analyse clinique thematique ; les protocoles du Rorschach et du TAT sont analyses selon la methode d’interpretation de l’Ecole Francaise referee a la theorie psychanalytique du fonctionnement psychique. Le materiel issu des rencontres avec deux patientes diagnostiquees a l’âge de 17 ans et ayant presente dans la suite de cette annonce une prise de poids de 10 kg est ici compare de maniere approfondie. Resultats Le reperage de contrastes en termes de problematiques et de niveaux d’elaboration entre l’entretien et les protocoles projectifs est saisissant pour chaque patiente. A travers l’analyse de l’entretien, le symptome alimentaire de la patiente 1 parait survenir dans un contexte psychique ou l’interiorite feminine semble irrepresentable. Les protocoles projectifs revelent a l’inverse l’acces a un travail du feminin conflictuel et symbolise. De meme, le discours de la patiente 2 sur son symptome est a premiere vue bien plus elabore que celui de la patiente 1 puisque celle-ci etablit un lien subjectif entre le renoncement au projet de maternite implique par l’annonce du MRKH et la dimension compensatoire procuree par la prise de poids. Pourtant, le contraste offert par les tests projectifs dont les productions traduisent au contraire les fragilites identitaires et une insuffisante symbolisation du sexuel temoigne de la valeur defensive de l’exces de symbolisation de son discours manifeste dans l’entretien. Discussion Ces contrastes amenent a envisager le remplissage alimentaire comme une tentative de traitement d’une sexualite feminine deja conflictuelle voire en impasse avant la decouverte du MRKH. Ses accents traumatiques sont reactualises et potentialises a la faveur de l’annonce diagnostique. Les differents niveaux de problematiques reperes peuvent cohabiter chez une meme femme, qu’il s’agisse d’un feminin ni construit ni integre, d’un impossible investissement du corps interne ou d’un contre-investissement de l’impossible maternite. Dans ce contexte, l’etiopathogenie de la prise de poids qui succede a l’annonce du diagnostic est pour chaque jeune fille singuliere mais toujours en lien avec un feminin et/ou un maternel atteint. Conclusion En conclusion, si la prise de poids qui suit le diagnostic traduit une entrave voire une impasse (eventuellement ponctuelle) du traitement psychique de ses effets, cette annonce medicale a l’adolescence peut constituer une nouvelle chance pour ces jeunes filles, celle d’un apres-coup a la valeur potentiellement mutative.

Monoclonal immunoglobulin M (IgM) anti-myelin-associated glycoprotein (MAG) neuropathy is a rare disabling condition, most commonly treated with rituximab monotherapy (R), which leads to neurological improvement in only 30%-50% of patients. The combination of rituximab plus chemotherapy has been proven to improve the level of responses. We studied the outcomes of anti-MAG neuropathy patients treated either by R, or by immunochemotherapy (ICT) in our centre, focusing on the incidence of the first neurological response evaluated by the modified Rankin scale (mRS). From 2011 to 2018, 64 patients were studied: 34 were treated with R and 30 with ICT. According to our treatment decision-making process, the median mRS was higher in the ICT group (mRS 2) than in the R group (mRS 1). At one year, improvements of the mRS rates were 46% and 18% in the ICT and R groups of patients respectively, with median times to response of eight and 13 months (p = 0.023). Adverse effects were higher in the ICT group: 62% vs 15% (p ˂ 0.01), all grades included. One secondary acute leukaemia occurred five years after treatment with ICT. In conclusion, ICT may be used as a valid option for patients with rapidly progressive and/or severe anti-MAG neuropathy symptoms.

Home respiratory equipment (HRE) designed for the management of chronic respiratory failure includes oxygen therapy (OThe French open access national health insurance aggregated data was used to estimate the evolution of theses parameters from 2006 to 2019.The number of patients treated by HRE increased by 117% between 2006 and 2019, reaching a total of 245,896 patients (367/100,000). Prescriptions for OOur results highlighted the high rate of HRE prescription, but with cost control as a result of adapted health policies.

Purpose: Describe the clinical and virological characteristics of viral necrotizing retinitis (VNR) and assess its prognostic factors. Methods: Retrospective study (Pitié Salpêtrière Hospital, Paris) of consecutive VNR patients diagnosed and monitored by qPCR on aqueous humor between 2015 and 2019. All patients received induction therapy with intravenous +/− intravitreal injections (IVI) of antivirals. Results: Forty-one eyes of 37 patients with a mean age of 56 years were included. Involved viruses were VZV (44%), CMV (37%) and HSV2 (19%). Acute retinal necrosis represented 51%, progressive outer retinal necrosis 12% and CMV retinitis 37% of eyes. Forty-six percent of patients were immunocompromised. Median BCVA was 0.7 LogMAR at baseline and 0.8 LogMAR after an average of 14.1 months. VNR bilateralized in 27% of cases after 32 months. Retinal detachment (RD) occurred in 27% of cases after a mean duration of 98 days. Factors associated with a “poor BCVA” at 1 month were: advanced age, low baseline BCVA, high vitritis grade and viral load (VL) at baseline and the “slow responder” status (i.e., VL decrease

To compare computed high b-value diffusion-weighted images (c-DWI) derived from low b-value DWI images and acquired high b-value DWI (a-DWI), in overall image quality and prostate cancer detection rate. A total of 124 consecutive men with suspected prostate cancer (PCa) underwent diagnosis prostate MRI on a 3.0 T MR system using a 32-channel phased-array torso coil. Among them, 63 underwent prostate biopsy. MRI protocol included 3DT2w images, high resolution Fov Optimized and Constrained Undistorted Single-Shot (FOCUS™) DWI images with b-values of 100, 400, 800, and 2000 s/mm2 and dynamic contrast enhanced images. C-DWI images (2000 and 2500 s/mm2) were derived from the three lower acquired b-value DWI images using a mono-exponential diffusion decay. C-DWI and acquired high b-value DWI (a-DWI) (2000 s/mm2) were compared for image quality (background signal suppression, anatomic clarity, ghosting, distortion) and tumor conspicuity by four radiologists. C-DWIs demonstrated higher rating than a-DWIs for overall image quality despite worsened ghosting. In patients with a biopsy, similar detection rate was observed while conspicuity was better with c-DWI (p

Objective Venoarterial extracorporeal membrane oxygenation (VA-ECMO) commonly is used to manage refractory cardiogenic shock after cardiac surgery, with 31% to 76% of patients successfully weaned off their ECMO. However, it is associated with high mortality rates, and 20% to 65% of weaned patients do not survive to hospital discharge. This study aimed to assess the incidence of ECMO weaning-related shock, the risk factors, and prognosis in the intensive care unit (ICU). Design Retrospective observational cohort study. Setting Surgical ICU of Cardiology Institute of Pitie-Salpetriere University Hospital (Paris-France). Participants Patients who were assisted with a peripheral VA-ECMO from January 2015 to December 2017 were included. Patients with venovenous, central, or right ECMO were excluded. Measurements The authors collected data on patients’ characteristics, during and after surgery. The indications for VA-ECMO implantation were ventricular dysfunction, primary graft dysfunction, and refractory cardiac arrest. Weaning-related shock was defined as the need to introduce or increase the dose of catecholamine at ECMO explantation or in the following week. Results After weaning off VA-ECMO, 56 of 146 patients (38.4%) presented weaning-related shock: 55% were septic shocks, 12.5 % were caused by right ventricle failure, and 7.1% by hemorrhage. ICU mortality was 42% versus 8% in patients who did not present shock. Multivariate analysis showed that patients with pulmonary hypertension and those with norepinephrine before weaning were more likely to develop shock. Conclusion ECMO weaning-related shock is frequent in patients with refractory cardiogenic shock after cardiac surgery. This is most commonly caused by sepsis and causes higher mortality rates, calling for further evaluation.

Background Data from nonrandomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against coronavirus disease 2019 (COVID-19). Methods We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe COVID-19 in a French university hospital. Patients who received hydroxychloroquine (200 mg 3 times daily dosage for 10 days) on a compassionate basis in addition to standard of care (SOC) were compared with patients without contraindications to hydroxychloroquine who received SOC alone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission ≤ 7 days, Charlson comorbidity index, medical history of arterial hypertension, obesity, National Early Warning Score 2 (NEWS2) score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. Results Data from 89 patients with laboratory-confirmed COVID-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOC alone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxychloroquine was not associated with a significantly reduced risk of unfavorable outcome (hazard ratio, 0.90 [95% confidence interval, .38–2.1], P = .81). Overall survival was not significantly different between the 2 groups (hazard ratio, 0.89 [0.23; 3.47], P = 1). Conclusion In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC. Unmeasured confounders may have persisted however, despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of COVID-19. In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC.

Maternal 25-hydroxyvitamin D (25-OHD) deficiency during pregnancy may increase the risk of preterm and small-for-gestational age (SGA) birth, but studies report conflicting results. We used a multicenter prospective cohort of 2813 pregnant women assessed for 25-OHD levels in the first trimester of pregnancy to investigate the association between maternal 25-OHD concentrations and risks of preterm birth (&lt, 37 weeks) and SGA (birthweight &lt, 10th percentile). Odds ratios were adjusted (aOR) for potential cofounders overall and among women with light and dark skin separately, based on the Fitzpatrick scale. 25-OHD concentrations were &lt, 20 ng/mL for 45.1% of the cohort. A total of 6.7% of women had a preterm birth. The aOR for preterm birth associated with the 1st quartile of 25-OHD concentrations compared to the 4th quartile was 1.53 (95% confidence interval (CI): 0.97&ndash, 2.43). In stratified analyses, an association was observed for women with darker skin (aOR = 2.89 (95% CI: 1.02&ndash, 8.18)), and no association with lighter skin. A total of 11.9% of births were SGA and there was no association overall or by skin color. Our results do not provide support for an association between maternal first trimester 25-OHD deficiency and risk of preterm or SGA birth overall, the association with preterm birth risk among women with darker skin requires further investigation.

This study analyzes the preoperative risk factors for intra-operative bleeding in our recent series of pediatric LTs. Between November 2009 and November 2014, 84 consecutive isolated pediatric LTs were performed in 81 children. Potential preoperative predictive factors for bleeding, amount of intra-operative transfusions, postoperative course, and outcome were recorded. Cutoff point for intra-operative HBL was defined as intra-operative RBC transfusions ≥1 TBV. Twenty-six patients (31%) had intra-operative HBL. One-year patient survival after LT was 66.7% (CI 95%=[50.2-88.5]) in HBL patients and 83.8% (CI 95%=[74.6-94.1]) in the others (P=.054). Among 13 potential preoperative risk factors, three of them were identified as independent predictors of high intra-operative bleeding: abdominal surgical procedure(s) prior to LT, factor V level ≤30% before transplantation, and ex situ parenchymal transsection of the liver graft. Based on these findings, we propose a simple score to predict the individual hemorrhagic risk related to each patient and graft association. This score may help to better anticipate intra-operative bleeding and improve patient's management.

Background: The aim of our study was to describe a large population with anomalies involving the SHOX region, responsible for idiopathic short stature and Léri-Weill dyschondrosteosis (LWD), and to identify a possible genotype/phenotype correlation. Methods: We performed a retrospective multicenter study on French subjects with a SHOX region anomaly diagnosed by multiplex ligation-dependent probe amplification or Sanger sequencing. Phenotypes were collected in each of the 7 genetic laboratories practicing this technique for SHOX analysis. Results: Among 205 index cases and 100 related cases, 91.3% had LWD. For index cases, median age at evaluation was 11.7 (9.0; 15.9) years and mean height standard deviation score was -2.3 ± 1.1. A deletion of either SHOX or PAR1 or both was found in 74% of patients. Duplications and point mutations/indels affected 8 and 18% of the population, respectively. Genotype-phenotype correlation showed that deletions were more frequently associated with Madelung deformity and mesomelic shortening in girls, as well as with presence of radiologic anomalies, than duplications. Conclusions: Our results highlight genotype-phenotype relationships in the French population with a SHOX defect and provide new information showing that clinical expression is milder in cases of duplication compared to deletions.

Background Sedative-hypnotics (SHs) are widely used in France but there are no available data addressing their prescription specifically in hospitalized older patients. The objective is thus to determine the cumulative incidence of sedative-hypnotic (SH) medications initialized during a hospital stay of older patients, the proportion of SH renewal at discharge among these patients and to study associated risk factors. Methods We conducted a retrospective observational study in six internal medicine units and six acute geriatric units in eight hospitals (France). We included 1194 inpatients aged 65 and older without SH medications prior to hospitalization. Data were obtained from patients’ electronic pharmaceutical records. Primary outcome was the cumulative incidence of SH initiation in the study units. Secondary outcomes were the proportion of SH renewal at discharge and risk factors for SH initiation and renewal at discharge (patient characteristics, hospital organization). A Cox regression model was used to study risk factors for SH initiation. A mixed effects logistic regression was used to study risk factors for SH renewal at discharge. Results SH initiation occurred in 21.5% of participants 20 days after admission. SH renewal at discharge occurred in 38.7% of patients who had initiated it during their stay and were discharged home and in 56.0% of patients discharged to rehabilitation facilities. Neither patients’ characteristics nor hospital organization patterns was associated with SH initiation. SH initiation after the first six days after admission was associated with a lower risk of SH renewal in patients discharged to rehabilitation facilities (OR = 0.19, 95% CI: [0.04–0.80]). Conclusions Hospitalization is a period at risk for SH initiation. The implementation of interventions promoting good use of SHs is thus of first importance in hospitals. Specific attention should be paid to patients discharged to rehabilitation facilities. Electronic supplementary material The online version of this article (10.1186/s12877-018-0972-3) contains supplementary material, which is available to authorized users.

Vitamin D is thought to be involved in the pathogenesis of preeclampsia. To evaluate the relationship between vitamin D insufficiency in the first trimester of pregnancy and preeclampsia.Nested case-control study (FEPED study) in type 3 obstetrical units. Pregnant women from 10 to 15 WA. For each patient with preeclampsia, 4 controls were selected from the cohort and matched by parity, skin color, maternal age, season and BMI. The main outcome measure was serum 25(OH)D status in the first trimester.83 cases of preeclampsia were matched with 319 controls. Mean 25(OH)D levels in the first trimester were 20.1 ± 9.3 ng/mL in cases and 22.3 ± 11.1 ng/mL in controls (p = 0.09). The risk for preeclampsia with 25(OH)D level ≥30 ng/mL in the first trimester was decreased, but did not achieve statistical significance (OR, 0.57; 95% CI, 0.30-1.01; p = 0.09). High 25(OH)D during the 3rd trimester was associated with a significantly decreased risk of preeclampsia (OR, 0.43; 95%CI, 0.23-0.80; p = 0.008). When women with 25(OH)D levels30 ng/mL both in the first and 3rd trimesters ("low-low") were taken as references, OR for preeclampsia was 0.59 (95% CI, 0.31-1.14; p = 0.12) for "low-high" or "high-low" women and 0.34 (95% CI, 0.13-0.86; p = 0.02) for "high-high" women.No significant association between preeclampsia and vitamin D insufficiency in the first trimester was evidenced. However, women with vitamin D sufficiency during the 3rd trimester and both in the first and 3rd trimesters had a significantly lower risk of preeclampsia.

ObjectivesTo assess the efficacy and safety of adalimumab on uveitis in patients with early onset, chronic, juvenile idiopathic arthritis (JIA)-associated or idiopathic anterior uveitis and an inadequate response to topical steroids and methotrexate (MTX).MethodsPatients aged 4 years or more with ocular inflammation quantified by laser flare photometry (LFP) ≥30 photon units/ms were double-blindly randomised (1:1) to 2 groups, one treated with placebo and one with adalimumab subcutaneously at a dose of 24 mg/m2 in patients aged ResultsAt M2, among 31 patients included in intention-to-treat analysis, there were 9/16 responders on adalimumab and 3/15 on placebo (P=0.038, Χ2 test; relative risk=2.81, 95% CI 0.94 to 8.45; risk difference: 36.3%, 95% CI 2.1 to 60.6); there was no significant difference using the Standardised Uveitis Nomenclature classification criteria of improvement. Thirty patients continued the trial after M2 and received adalimumab (open-label phase), 29 reached M12. There were seven serious adverse events none related to study treatment.ConclusionsThis trial is in favour of using adalimumab in patients with early onset, chronic anterior uveitis, which is in most cases associated with JIA, in case of inadequate response to topical therapy and MTX. LFP could be a valuable tool to assess early treatment efficacy.Trial registration numberNCT01385826.

BACKGROUND Results of genetic have led to off-label glibenclamide treatment in patients with neonatal diabetes (NDM) because of potassium channel mutations. No pediatric form of glibenclamide was available. Glibenclamide was designated an orphan drug designation for NDM and a suspension was developed. As a part of the pediatric plan investigation, we assessed its acceptability, efficiency, and safety. METHODS In this Phase II, prospective, non-randomized, single-center study, patient received glibenclamide tablets for 1 month then the suspension for 3 months. We assessed acceptability using hedonic scales and patient questionnaires, effectiveness using glycated hemoglobin (HbA1C) assays and safety based on hypo and hyperglycemia, and other adverse events. RESULTS We included 10 patients (0.1-16.2 years, 6

International audience; Background We aimed to evaluate whether pre and perinatal education of pregnant women would reduce childhood overweight. Methods Four French centers included women at 25 kg/m(2) before pregnancy. Patients were randomized to a control group (routine care including at least one dietary visit) or an intervention group (2 individuals (26 and 30 GW) and 4 group sessions (21, 28, 35 GW, 2 months postpartum)) aimed at educating the future mother regarding infant and maternal nutrition. The primary objective was to reduce post-natal excessive weight gain in the infant from birth to 2 years (NCT00804765). This project was funded by a grant from the National Programme for Hospital Research (PHRC-2007 French Ministry of Health). Results We included 275 women (BMI: 32.5 kg/m(2)). The rate of post-natal excessive weight gain was similar in the intervention (n = 132) and control (n = 136) groups by intention to treat (ITT: 59.1% vs 60.3% respectively, p = 0.84) in available data (AD, n = 206) and by per-protocol analysis (PP, n = 177). Two years after delivery, normalization of maternal BMI and number of infants with BMI < 19 kg/m(2) were not significantly different in the interventional group in ITT and in the control group. Although not significantly different in ITT, normalization of maternal BMI was more frequent in AD (n = 149: 12.9% vs 3.8%, p = 0.04) and 2-year-old infant BMIs were less likely to be > 19 kg/m(2) in the intervention group in AD (n = 204: 0% vs 6.8%, p = 0.014) and PP (n = 176: 0% vs 6.4%, p = 0.03). Conclusions An education and nutritional counseling program for overweight women, starting after 3 months of gestation, did not significantly change post-natal excessive weight gain of infants or prevent overweight in mothers and children 2 years after delivery.

The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P

The aim of our study was to describe a large population with anomalies involving the SHOX region, responsible for idiopathic short stature and Léri-Weill dyschondrosteosis (LWD), and to identify a possible genotype/phenotype correlation.We performed a retrospective multicenter study on French subjects with a SHOX region anomaly diagnosed by multiplex ligation-dependent probe amplification or Sanger sequencing. Phenotypes were collected in each of the 7 genetic laboratories practicing this technique for SHOX analysis.Among 205 index cases and 100 related cases, 91.3% had LWD. For index cases, median age at evaluation was 11.7 (9.0; 15.9) years and mean height standard deviation score was -2.3 ± 1.1. A deletion of either SHOX or PAR1 or both was found in 74% of patients. Duplications and point mutations/indels affected 8 and 18% of the population, respectively. Genotype-phenotype correlation showed that deletions were more frequently associated with Madelung deformity and mesomelic shortening in girls, as well as with presence of radiologic anomalies, than duplications.Our results highlight genotype-phenotype relationships in the French population with a SHOX defect and provide new information showing that clinical expression is milder in cases of duplication compared to deletions.

Background: The authors aimed to collect all brain magnetic resonance imaging (MRI) performed in critically ill children in the authors’ medical pediatric intensive care unit over a 2-year period (2012-2013) to (1) describe the findings and (2) assess its contribution on practical patient care. Methods: This is a single-center and retrospective study. All children without traumatic brain injury who underwent a brain MRI during pediatric intensive care unit stays were included. To assess the exam’s contribution, the patient’s medical condition at the time of the MRI exam was blindly and separately exposed to a pediatric neurologist and a pediatric intensivist. Results: During the study period, 87 patients (7.5%) underwent a brain MRI. Median age was 4 months and 13 children (14.9%) died in pediatric intensive care unit. The most common final diagnosis was postanoxic encephalopathy. Brain MRI was abnormal in 68 patients (78.2%). No serious adverse event occurred during the transport. The neurologist and the intensivist considered brain MRI as indicated during pediatric intensive care unit stay in 65 (74.7%) and 68 patients (78.2%). They deemed that brain MRI had a diagnostic contribution in 76 (87.4%) and 60 (69.0%) patients, respectively. A therapeutic change consecutive to MRI findings occurred in 19 patients (21.8%) and MRI results were associated with a decision to withdraw life-sustaining treatment in 21 patients (24.1%). Conclusion: Brain MRI is one component of neuromonitoring, and this study suggests a substantial diagnostic contribution, although its therapeutic impact appears limited to specific diagnoses.

Vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome can be managed either by various surgeries or dilation. The choice still depends on surgeon's preferences rather than on quality comparative studies and validated protocols.We sought to compare dilation and surgical management of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome, in terms of quality of life, anatomical results, and complications in a large multicenter population.Our multicenter study included 131 patients18 years, at least 1 year after completing vaginal agenesis management. All had an independent gynecological evaluation including a standardized pelvic exam, and completed the World Health Organization Quality of Life instrument (general quality of life) as well as the Female Sexual Function Index and Female Sexual Distress Scale-Revised (sexual quality of life) scales. Groups were: surgery (N = 84), dilation therapy (N = 26), and intercourse (N = 20). One patient was secondarily excluded because of incomplete surgical data. For statistics, data were compared using analysis of variance, Student, Kruskal-Wallis, Wilcoxon, and Student exact test.Mean age was 26.5 ± 5.5 years at inclusion. In all groups, World Health Organization Quality of Life scores were not different between patients and the general population except for lower psychosocial health and social relationship scores (which were not different between groups). Global Female Sexual Function Index scores were significantly lower in the surgery and dilation therapy groups (median 26 range [2.8-34.8] and 24.7 [2.6-34.4], respectively) than the intercourse group (30.2 [7.8-34.8], P = .044), which had a higher score only in the satisfaction dimension (P = .004). However, the scores in the other dimensions of Female Sexual Function Index were not different between groups. The Female Sexual Distress Scale-Revised median scores were, respectively, 17 [0-52], 20 [0-47], and 10 [10-40] in the surgery, dilation therapy, and intercourse groups (P = .38), with sexual distress in 71% of patients. Median vaginal depth was shorter in dilatation therapy group (9.6 cm [5.5-12]) compared to surgery group (11 cm [6-15]) and intercourse group (11 cm [6-12.5]) (P = .039), but remained within normal ranges. One bias in the surgery group was the high number of sigmoid vaginoplasties (57/84, 68%), but no differences were observed between surgeries. Only 4 patients achieved vaginas6.5 cm. Delay between management and first intercourse was 6 months (not significant). Seventy patients (53%) had dyspareunia (not significant), and 17 patients all from the surgery group had an abnormal pelvic exam. In the surgery group, 34 patients (40.5%) had complications, requiring 20 secondary surgeries in 17 patients, and 35 (42%) needed postoperative dilation. In the dilation therapy group, 13 (50%) needed maintenance dilation.Surgery is not superior to therapeutic or intercourse dilation, bears complications, and should therefore be only a second-line treatment. Psychological counseling is mandatory at diagnosis and during therapeutic management.

Importance Cell-free DNA (cfDNA) tests are increasingly being offered to women in the first trimester of pregnancies at a high risk of trisomy 21 to decrease the number of required invasive fetal karyotyping procedures and their associated miscarriages. The effect of this strategy has not been evaluated. Objective To compare the rates of miscarriage following invasive procedures only in the case of positive cfDNA test results vs immediate invasive testing procedures (amniocentesis or chorionic villus sampling) in women with pregnancies at high risk of trisomy 21 as identified by first-trimester combined screening. Design, setting, and participants Randomized clinical trial conducted from April 8, 2014, to April 7, 2016, in 57 centers in France among 2111 women with pregnancies with a risk of trisomy 21 between 1 in 5 and 1 in 250 following combined first-trimester screening. Interventions Patients were randomized to receive either cfDNA testing followed by invasive testing procedures only when cfDNA tests results were positive (n = 1034) or to receive immediate invasive testing procedures (n = 1017). The cfDNA testing was performed using an in-house validated method based on next-generation sequencing. Main outcomes and measures The primary outcome was number of miscarriages before 24 weeks' gestation. Secondary outcomes included cfDNA testing detection rate for trisomy 21. The primary outcome underwent 1-sided testing; secondary outcomes underwent 2-sided testing. Results Among 2051 women who were randomized and analyzed (mean age, 36.3 [SD, 5.0] years), 1997 (97.4%) completed the trial. The miscarriage rate was not significantly different between groups at 8 (0.8%) vs 8 (0.8%), for a risk difference of -0.03% (1-sided 95% CI, -0.68% to ∞; P = .47). The cfDNA detection rate for trisomy 21 was 100% (95% CI, 87.2%-100%). Conclusions and relevance Among women with pregnancies at high risk of trisomy 21, offering cfDNA screening, followed by invasive testing if cfDNA test results were positive, compared with invasive testing procedures alone, did not result in a significant reduction in miscarriage before 24 weeks. The study may have been underpowered to detect clinically important differences in miscarriage rates. Trial registration ClinicalTrials.gov Identifier: NCT02127515.

Background. Cardiac iron overload is the major cause for death in regularly transfused thalassemic (Thal) patients. Its impact in myelodysplastic syndrome (MDS) patients is debated. Heart seems to be spared in regularly transfused patients with sickle cell anemia (SCA), which is supposed to be related to a later onset on transfusions and to the use of erythrocytapheresis rather than simple transfusion. Our aim was to assess the prevalence of cardiac iron overload, defined as a T2*cardiovascular magnetic resonance (MR) Patients and methods. Patients were enrolled if they were regularly followed in a center where the exact number of erythrocyte concentrates (EC) could be obtained, had received in the previous year more than 8 EC, were older than 6 years (limit for MRI without sedation), had no known heart disease related to another pathology, and had given informed consent. All patients underwent 1.5T myocardial T2*MR imaging after validation of the procedures in the different sites. Assessment of Liver Iron Content (LIC) used two signal intensity ratio of gradient echo imaging (R2*) MRI protocols. Serum Non-Transferrin Bound Iron (NTBI) was measured by the FeROSTM eLPI kit, and serum hepcidin by LC-MSMS. Results. 20 Thal, 41 SCA and 25 MDS patients were evaluable. We divided SCA in 2 groups, according to the procedure recorded at the time of the study, manual exchange transfusion (G1, N = 30 patients), or erythrocytapheresis (G2, N=11 patients). We found cardiac overload in 0, 3 (15%), and 4 (16%) of SCA, Thal, and MDS patients respectively. Serum ferritins at beginning of chelation were not statistically different in all categories of patients, as well as Ferritin and LIC at the time of the study. Increased LIC and abnormal T2* were associated in Thal and MDS patients (p=0.04), with no correlation between abnormal T2* and parameters of transfusion and chelation. Plasmatic iron level was increased in Thal and MDS patients but remained at normal range in SCA patients. NTBI level was high in Thal and MDS but completely absent in SCA groups. The major discrepancy was in the values of hepcidin, which were collapsed in Thal, at normal range in SCA, and highly elevated in MDS patients. Discussion and conclusion. We confirm that SCA patients are relatively protected from cardiac iron overload. This results probably from massive consummation of iron through effective erythropoiesis, making toxic free iron (NTBI) less available in the circulation. In addition, since iron overload in SCA results from a massive outflow of hemoglobin (Hb) due to intravascular hemolysis and transfusion, the heme/Hb-bound iron must be efficiently handled in liver macrophages, limiting its release in the bloodstream. In Thal patients, underlying defects in erythropoietic processes, together with low hepcidin that stimulates intestinal iron absorption and increases NTBI, must provoke more organ damages. Hepcidin levels were high in MDS patients, suggesting that transfusion-dependent iron overload was a more effective regulator of hepcidin production than dyserythropoiesis. The % of T2* Finally, we observe that, in opposition with previous reports, SCA patients undergoing eythrocytapheresis may experience severe iron overload and need iron chelation. Table 1. Thal SCA G1 SCA G2 MDS p Age at beginning of transfusion (yrs) 8.5[0-45] 7[0-45] 16.5[1-55] 66[38-83] Disclosures De Montalembert: Addmedica: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau. Guerci-Bresler:ARIAD: Speakers Bureau; BMS: Speakers Bureau; Novartis: Speakers Bureau; PFIZER: Speakers Bureau.

Objectif Les anomalies de SHOX ont des consequences phenotypiques variables telles qu’une petite taille idiopathique ou la dyschondrosteose de Leri-Weill. Le but de notre etude multicentrique observationnelle etait de decrire les phenotypes et les genotypes d’une grande population avec anomalie de SHOX, ou de ses regions regulatrices, et d’identifier une possible correlation phenotype-genotype. Materiel et methodes Les phenotypes et les genotypes ont ete recueillis entre 2009 et 2013 dans 7 laboratoires francais utilisant la technique MLPA a visee diagnostique. Le sequencage du gene a parfois ete effectue pour detecter une mutation ponctuelle quand la MLPA etait normale. Resultats Au total, 305 patients ont ete ainsi diagnostiques, 91,3 % avaient une dyschondrosteose clinique. La taille mediane en DS etait de –2,1. Les filles etaient diagnostiquees plus tot que les garcons (12,7 vs 15,2 ans, p = 0,04), etaient plus petites (–2,4 DS vs –2,0 DS, p = 0,007) et avaient plus frequemment une deformation de Madelung (78,2 % vs 21,7 %, p = 0,0004). Les anomalies genetiques etaient: 40,3 % de deletions de SHOX ± PAR1, 33,7 % de deletions de PAR1, 5,9 % de duplications de PAR1, 2,0 % de duplications de SHOX + PAR1 et 18 % de mutations ponctuelles. Chez les filles, les deletions etaient plus frequemment associees avec une deformation de Madelung, un avant-bras court et des signes radiologiques que les duplications (p = 0,02, p = 0,006 et p = 0,008). Conclusion Nous avons realise une description de la population francaise mutee pour SHOX et demontre que les phenotypes chez les garcons sont moins severes que chez les filles.