A randomized double-blind placebo-controlled trial of low-dose interleukin-2 in relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is associated with regulatory T cells (Tregs) insufficiency while low-dose interleukin-2 (IL2LD) activates Tregs and reduces disease activity in autoimmune diseases. METHODS: We aimed at addressing whether IL2LD improved Tregs from MS patients. MS-IL2 was a single-center double-blind phase-2 study. Thirty patients (mean [SD] age 36.8 years [8.3], 16 female) with relapsing-remitting MS with new MRI lesions within 6 months before inclusion were randomly assigned in a 1:1 ratio to placebo or IL-2 at 1 million IU, daily for 5 days and then fortnightly for 6 months. The primary endpoint was change in Tregs at day-5. RESULTS: Unlike previous trials of IL2LD in more than 20 different autoimmune diseases, Tregs were not expanded at day-5 in IL2LD group, but only at day-15 (median [IQR] fold change from baseline: 1.26 [1.21-1.33] in IL2LD group; 1.01 [0.95-1.05] in placebo group, p < 0.001). At day-5, however, Tregs had acquired an activated phenotype (fold change of CD25 expression in Tregs: 2.17 [1.70-3.55] in IL2LD versus 0.97 [0.86-1.28] in placebo group, p < 0.0001). Regulator/effector T cells ratio remained elevated throughout treatment period in the IL2LD group (p < 0.001). Number of new active brain lesions and of relapses tended to be reduced in IL2LD treated patients, but the difference did not reach significance in this trial not powered to detect clinical efficacy. CONCLUSION: The effect of IL2LD on Tregs in MS patients was modest and delayed, compared to other auto-immune diseases. This, together with findings that Tregs improve remyelination in MS models and recent reports of IL2LD efficacy in amyotrophic lateral sclerosis, warrants larger studies of IL2LD in MS, notably with increased dosages and/or modified modalities of administration. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT02424396; EU Clinical trials Register: 2014-000088-42.

Design of a prospective, longitudinal cohort of people living with type 1 diabetes exploring factors associated with the residual cardiovascular risk and other diabetes-related complications: The SFDT1 study.

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.

Impact of oxygen tension according to embryo stage of development: a prospective randomized study.

Human embryo culture under 2-8% O2 is recommended by ESHRE revised guidelines for good practices in IVF labs. Nevertheless, notably due to the higher costs of embryo culture under hypoxia, some laboratories perform embryo culture under atmospheric O2 tension (around 20%). Furthermore, recent meta-analyses concluded with low evidence to a superiority of hypoxia on IVF/ICSI outcomes. Interestingly, a study on mice embryos suggested that oxidative stress (OS) might only have an adverse impact on embryos at cleavage stage. Hence, we aimed to demonstrate for the first time in human embryos that OS has a negative impact only at cleavage stage and that sequential culture conditions (5% O2 from Day 0 to Day 2/3, then «conventional¼ conditions at 20% O2 until blastocyst stage) might be a valuable option for human embryo culture. 773 IVF/ICSI cycles were included in this randomized clinical trial from January 2016 to April 2018. At Day 0 (D0), patients were randomized using a 1:2 allocation ratio between group A (20% O2; n = 265) and group B (5% O2; n = 508). Extended culture (EC) was performed when ≥ 5 Day 2-good-quality-embryos were available (n = 88 in group A (20% O2)). In subgroup B, 195 EC cycles were randomized again at Day 2 (using 1:1 ratio) into groups B' (5% O2 until Day 6 (n = 101)) or C (switch to 20% O2 from Day 2 to Day 6 (n = 94). Fertilization rate, cleavage-stage quality Day 2-top-quality-embryo (D2-TQE), blastocyst quality (Day 5-top-quality-blastocyst (D5-TQB) and implantation rate (IR) were compared between groups A and B (= cleavage-stage analysis), or A(20% O2), B'(5% O2) and C(5%-to-20% O2). Overall, characteristics were similar between groups A and B. Significantly higher rates of early-cleaved embryos, top-quality and good-quality embryos on Day 2 were obtained in group B compared to group A (P < 0.05). This association between oxygen tension and embryo quality at D2 was confirmed using an adjusted model (P < 0.05). Regarding blastocyst quality, culture under 20% O2 from Day 0 to Day 6 (group A) resulted in significantly lower Day 5-TQB number and rates (P < 0.05) compared to both groups B' and C. Furthermore, blastocyst quality was statistically equivalent between groups B' and C (P = 0.45). At Day 6, TQB numbers and rates were also significantly higher in groups B' and C compared to group A (P < 0.05). These results were confirmed analyzing adjusted mean differences for number of Day 5 and Day 6 top quality embryos obtained in group A when compared to those respectively in groups B' and C (P < 0.05). No difference in clinical outcomes following blastocyst transfers was observed. These results would encourage to systematically culture embryos under hypoxia at least during early development stages, since OS might be detrimental exclusively before embryonic genome activation.

COgnitive enhancement and consumption of psychoactive Substances among Youth Students (COSYS): a cross-sectional study in France.

OBJECTIVES: This descriptive and analytical study investigated the consumption rates of psychoactive substances among individuals aged 18-25 years in France. More specifically, it enabled assessment of the extent of the neuroenhancement (NE) phenomenon among students in France (including study of the misuse of psychostimulant medicines). STUDY DESIGN: COgnitive enhancement and consumption of psychoactive Substances among Youth Students (COSYS) is a cross-sectional survey of students in France. METHODS: Between January and June 2017, a questionnaire was mailed to students. All questionnaires were completed anonymously and included questions regarding the use of all kind of psychoactive substances, motivations for use and socio-economic situations. Statistics for all variables and the results of a multiple correspondence analysis (MCA) are presented. RESULTS: This study recorded 46,203 respondents, mostly in universities (>60%), mostly women (63.4%), with an average age of 21.4 years. In terms of substance use, medications were cited in the third position after alcohol and tobacco by women (22.48%) and in the fourth position after alcohol, tobacco and cannabis by men (15.14%). Among medications, opiates were the most frequently used, followed by benzodiazepines. Students who declared a non-medical use (NMU) of drugs obtained these through various ways (e.g. family medicine cabinet, a friend, a dealer or via the Internet), or by increasing their recommended doses (e.g. codeine). In total, 18.6% of students consumed psychoactive substances for 'stress management' and 14.1% for 'sleep management'. Results indicated that NE in students is a problem, with 18.6% of students in the COSYS survey confirming the use of psychoactive substances for this reason. There was a very low prevalence for psychostimulant medications (0.57% of men), mostly NMU (67%). MCA yielded three different profiles (doping candidate, experimenter and psychiatric profile) of psychostimulant users, which complicates the implementation of prevention programmes. CONCLUSIONS: It is evident that NMU and 'conventional' use of medications are highly prevalent in French students, especially females. NMU is associated with substance use disorders, psychopathology and suicidality. Social norms and social media increase NMU of psychoactive substances, but also provide a potential platform for anti-NMU campaigns. CLINICAL TRIAL REGISTRATION NUMBER: NCT02954679.

Security and reliability of CUSTOMBONE cranioplasties: A prospective multicentric study.

BACKGROUND: Repairing bone defects generated by craniectomy is a major therapeutic challenge in terms of bone consolidation as well as functional and cognitive recovery. Furthermore, these surgical procedures are often grafted with complications such as infections, breaches, displacements and rejections leading to failure and thus explantation of the prosthesis. OBJECTIVE: To evaluate cumulative explantation and infection rates following the implantation of a tailored cranioplasty CUSTOMBONE prosthesis made of porous hydroxyapatite. One hundred and ten consecutive patients requiring cranial reconstruction for a bone defect were prospectively included in a multicenter study constituted of 21 centres between December 2012 and July 2014. Follow-up lasted 2 years. RESULTS: Mean age of patients included in the study was 42±15 years old (y.o), composed mainly by men (57.27%). Explantations of the CUSTOMBONE prosthesis were performed in 13/110 (11.8%) patients, significantly due to infections: 9/13 (69.2%) (p<0.0001), with 2 (15.4%) implant fracture, 1 (7.7%) skin defect and 1 (7.7%) following the mobilization of the implant. Cumulative explantation rates were successively 4.6% (SD 2.0), 7.4% (SD 2.5), 9.4% (SD 2.8) and 11.8% (SD 2.9%) at 2, 6, 12 and 24 months. Infections were identified in 16/110 (14.5%): 8/16 (50%) superficial and 8/16 (50%) deep. None of the following elements, whether demographic characteristics, indications, size, location of the implant, redo surgery, co-morbidities or medical history, were statistically identified as risk factors for prosthesis explantation or infection. CONCLUSION: Our study provides relevant clinical evidence on the performance and safety of CUSTOMBONE prosthesis in cranial procedures. Complications that are difficulty incompressible mainly occur during the first 6 months, but can appear at a later stage (>1 year). Thus assiduous, regular and long-term surveillances are necessary.

Prognostic value of longitudinal strain and ejection fraction in Friedreich's ataxia.

BACKGROUND: Friedreich's ataxia (FA) is a rare autosomal recessive mitochondrial disease most commonly due to a triplet repeat expansion guanine-adenine-adenine (GAA) in the FXN gene. Cardiac disease is the major cause of death, patients with reduced left ventricular ejection fraction (LVEF) having the worse prognosis. Longitudinal strain (LS) appeared to be a better predictor of outcome than LVEF in different diseases. We compared the prognostic value of LS measured from the 4 chambers view to LVEF. METHODS: From 2003 to 2017 consecutive patients with FA were included and LS analysis was retrospectively performed. RESULTS: We studied 140 patients, with a median age of 34 (26-41) years (Q1-Q3) with age at onset of 14 (11-19) years and GAA repeats on the shorter allele of 600 (467-783) pb. Mean LS was 19.9 ± 5.0% and LVEF 64 ± 8%. After a mean follow-up of 7.4 ± 3.9 years, 14 patients died. In univariate Cox analysis, all-cause mortality was associated with: LS (HR 0.83; 95%CI, 0.75-0.91, p = 0.0002), LVEF (HR 0.30; 95%CI, 0.19-0.49, p < 0.0001), GAA repeats on the shorter allele (HR 1.29; 95%CI, 1.10-1.51, p = 0.002), age at onset (HR 0.87; 95%CI, 0.77-0.98, p = 0.018), LVSystolic Diameter (HR 1.17; 95%CI, 1.09-1.26, p < 0.0001), LVMass index (HR 1.02; 95%CI, 1.00-1.04, p = 0.027), and LVDiastolic Diameter (HR1.12; 95%CI, 1.01-1.23, p = 0.028). In multivariate analysis, LVEF was the only independent predictor of mortality (HR 0.41; 95%CI, 0.23-0.74, p = 0.0029). CONCLUSION: In FA, LS was not an independent predictor of mortality, LVEF remained the only independent predictor in the present study.

A Reappraisal of Outcome of Elective Surgery After Successful Non-Operative Management of an Intra-Abdominal Abscess Complicating Ileocolonic Crohn's Disease: A Subgroup Analysis of a Nationwide Prospective Cohort.

BACKGROUND AND AIMS: Few prospective data exist on outcomes of surgery in Crohn's disease [CD] complicated by an intra-abdominal abscess after resolution of this abscess by antibiotics optionally combined with drainage. METHODS: From 2013 to 2015, all patients undergoing elective surgery for CD after successful non-operative management of an intra-abdominal abscess [Abscess-CD group] were selected from a nationwide multicentre prospective cohort. Resolution of the abscess had to be computed tomography/magnetic resonance-proven prior to surgery. Abscess-CD group patients were 1:1 matched to uncomplicated CD [Non-Penetrating-CD group] using a propensity score. Postoperative results and long-term outcomes were compared between the two groups. RESULTS: Among 592 patients included in the registry, 63 [11%] fulfilled the inclusion criteria. The abscess measured 37 ±â€…20 mm and was primarily managed with antibiotics combined with drainage in 14 patients and nutritional support in 45 patients. At surgery, a residual fluid collection was found in 16 patients [25%]. Systemic steroids within 3 months before surgery [p = 0.013] and the absence of preoperative enteral support [p = 0.001] were identified as the two significant risk factors for the persistence of a fluid collection. After propensity score matching, there was no significant difference between the Abscess-CD and Non-Penetrating-CD groups in the rates of primary anastomosis [84% vs 90% respectively, p = 0.283], overall [28% vs 15% respectively, p = 0.077] and severe postoperative morbidity [7% vs 7% respectively, p = 1.000]. One-year recurrence rates for endoscopic recurrence were 41% in the Abscess-CD and 51% in the Non-Penetrating-CD group [p = 0.159]. CONCLUSIONS: Surgery after successful non-operative management of intra-abdominal abscess complicating CD provides good early and long-term outcomes.

Prognosis associated with initial care of increased fasting glucose in early pregnancy: A retrospective study.

AIM: To evaluate whether the initial care of women with fasting plasma glucose (FPG) levels at 5.1-6.9mmol/L before 22 weeks of gestation (WG), termed 'early fasting hyperglycaemia', is associated with fewer adverse outcomes than no initial care. METHODS: A total of 523 women with early fasting hyperglycaemia were retrospectively selected in our department (2012-2016) and separated into two groups: (i) those who received immediate care (n=255); and (ii) those who did not (n=268), but had an oral glucose tolerance test (OGTT) at or after 22 WG, with subsequent standard care if hyperglycaemia (by WHO criteria) was present. The number of cases of large-for-gestational age (LGA) infants, shoulder dystocia and preeclampsia with initial care of early fasting hyperglycaemia were compared after propensity score modelling and accounting for covariates. RESULTS: Of the 268 women with no initial care, 134 had hyperglycaemia after 22 WG and then received care. Women who received initial care vs those who did not were more likely to be insulin-treated during pregnancy (58.0% vs 20.9%, respectively; P<0.00001), gained less gestational weight (8.6±5.4kg vs 10.8±6.1kg, respectively; P<0.00001), had a lower rate of preeclampsia [1.2% vs 2.6%, respectively; adjusted odds ratio (aOR): 0.247 (0.082-0.759), P=0.01], and similar rates of LGA infants (12.2% vs 11.9%, respectively) and shoulder dystocia (1.6% vs 1.5%, respectively). When initial FPG levels were ≥5.5mmol/L (prespecified group, n=137), there was a lower rate of LGA infants [6.7% vs 16.1%, respectively; aOR: 0.332 (0.122-0.898); P=0.03]. CONCLUSION: Treating women with early fasting hyperglycaemia, especially when FPG is ≥5.5mmol/L, may improve pregnancy outcomes, although this now needs to be confirmed by randomized clinical trials.

Initially untreated fasting hyperglycaemia in early pregnancy: prognosis according to occurrence of gestational diabetes mellitus after 22 weeks' gestation: a case-control study.

AIMS: To evaluate the percentage of women with untreated fasting hyperglycaemia in early pregnancy who develop gestational diabetes mellitus after 22 weeks' gestation, the determinants of gestational diabetes development in such women and the prognosis of early fasting hyperglycaemia according to whether the women go on to develop gestational diabetes. METHODS: From a large cohort of women who delivered in our hospital between 2012 and 2016, we retrospectively selected all those who had untreated early fasting hyperglycaemia and separated them into a 'gestational diabetes' and a 'no-gestational diabetes' group according to oral glucose tolerance test results after 22 weeks' gestation. We compared the incidence of a predefined composite outcome (preeclampsia or large-for-gestational-age infant or shoulder dystocia or neonatal hypoglycaemia) in both groups. RESULTS: A total of 268 women (mean fasting plasma glucose 5.3 ± 0.3 mmol/l at a mean ± sd of 10.2 ± 4.2 weeks' gestation) were included. Gestational diabetes developed in 134 women and was independently associated with early fasting plasma glucose ≥ 5.5 mmol/l [odds ratio 3.16 (95% CI 1.57, 6.33)], age ≥ 30 years [odds ratio 2.78 (95% CI 1.46, 5.31)], preconception obesity [odds ratio 2.12 (95% CI 1.11, 4.02)], family history of diabetes [odds ratio 1.87 (95% CI 1.00, 3.50)] and current employment [odds ratio 0.46 (95% CI 0.26, 0.83)]. Despite treatment, gestational diabetes induced a significant increase in the composite outcome as compared to no gestational diabetes (odds ratio 2.16 [95% CI 1.08, 4.34]). The association disappeared after adjustment for risk factors. CONCLUSIONS: Only half of the women with early fasting hyperglycaemia and no specific care subsequently developed gestational diabetes, and these women had a poor prognosis despite gestational diabetes treatment. Poor prognosis was mostly attributable to risk factors. Our results suggest that only women with certain risk factors should be screened for early fasting hyperglycaemia.

Performance of a selective screening strategy for diagnosis of hyperglycaemia in pregnancy as defined by IADPSG/WHO criteria.

AIM: Our study evaluated the performance of a selective screening strategy for hyperglycaemia in pregnancy (HIP) based on the presence of risk factors (RFs; body mass index≥25kg/m2, age≥35years, family history of diabetes, personal history of HIP or macrosomic infant) to diagnose HIP and to predict HIP-related events. METHODS: Women with no known diabetes who had undergone complete universal screening (early, before 22weeks of gestation and, if normal, in the second part of pregnancy) at our department (2012-2016) were selected, resulting in four groups of women according to the presence of HIP and/or RFs, with a predefined composite endpoint (preeclampsia or large-for-gestational-age infant or shoulder dystocia). RESULTS: Included were 4518 women: 23.5% had HIP and 71.1% had at least one RF. The distribution among our four groups was: HIP-/RF- (n=1144); HIP-/RF+ (n=2313); HIP+/RF- (n=163); and HIP+/RF+ (n=898). HIP was more frequent when RFs were present rather than absent (33.1% vs 15.4%, respectively; P<0.001). Incidence of the composite endpoint differed significantly (P<0.0001) across groups [HIP-/RF- 6.3%; HIP-/RF+ 13.2%; HIP+/RF- 8.6%; and HIP+/RF+ 17.1% (HIP effect: P<0.05; RF effect: P<0.001; interaction HIP * RF: P=0.94)] and significantly increased with the number of RFs (no RF: 6.3%, 1 RF: 10.8%, 2 RFs: 14.7%, 3 RFs: 28.0%, 4-5 RFs: 25.0%; P<0.0001). CONCLUSION: RFs are predictive of HIP, although 15.4% of women with HIP have no RFs. Also, irrespective of HIP status, RFs are predictive of HIP-related events, suggesting that overweight/obesity, the only modifiable RFs, could be targets of interventions to improve pregnancy prognosis.

Use of a navigation system in endonasal surgery: Impact on surgical strategy and surgeon satisfaction. A prospective multicenter study.

OBJECTIVES: Surgical navigation systems (SNS) are now widely used in endoscopic endonasal surgery. Benefit, however, has not been fully studied. The objective of this study was to evaluate the impact of an SNS in terms of performance of the surgical procedure and of surgeon satisfaction, in a prospective multicenter study. MATERIALS AND METHODS: A multicenter prospective study included patients undergoing endoscopic endonasal surgery using the electromagnetic DigiPointeur® (DGP) SNS in 16 French hospitals. An observation form, completed by the surgeon immediately at end of procedure, included type of procedure, and any changes in strategy or extent of surgery related to use of the SNS. Surgeon satisfaction was rated on an analog scale, with self-assessment of stress experienced during the procedure. RESULTS: The study included 311 patients operated on by 36 surgeons in 16 French hospitals. Ethmoidectomy was the most frequent procedure (90%); tumor resection was performed in 5.1% of cases. The SNS enabled more extensive surgery in 81% of cases, in particular by identifying and opening additional cells (57% of cases). Mean satisfaction was 8.6/10; surgeons reported decreased surgical stress thanks to the SNS in 95% of cases. CONCLUSION: In this observational study, the use of an SNS increased the extent of surgery in 81% of cases, and had a positive impact on the stress perceived by the surgeon in 95% of cases.

Prospective, multicentric, comparative study between sleeve gastrectomy and Roux-en-Y gastric bypass, 277 patients, 3 years follow-up.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en Y gastric bypass (LRYGB) are commonly performed, but few studies have shown superiority of one strategy over the other. OBJECTIVE: Simultaneously compare LSG and LRYGB in terms of weight loss and morbimortality over a 36-month follow-up period. SETTING: University hospital and bariatric surgery centers, France. METHODS: Prospective, comparative study between LSG and RYGBP. The primary endpoint of this study was a joint hypothesis during the 36-month follow-up: the first primary outcome pertained to the frequency of patients with an excess weight loss (EWL) greater than 50% (% EWL>50%) after LSG or RYGB; the second primary outcome was defined as a composite endpoint of at least one major complication. Secondary objectives were regression of comorbidities and improvement in quality of life. RESULTS: Two hundred and seventy-seven patients were included (91 RYGBP, 186 LSG). The mean age was 41.1±11.1 years, and average preoperative body mass index of 45.3±5.5kg/m2. After 36months, the %EWL>50% was not inferior in the case of LSG (82.2%) relative to LRYGB (82.1%); while major complications rates were significantly higher in LRYGB (15.4%) vs. LSG (5.4%, P=0.005). After 36months, all secondary objectives were comparable between groups while only gastroesophageal reflux disease (GERD) increased in LSG group and decreased in LRYGB group. CONCLUSIONS: LSG was found non-inferior to LRYGB with respect to weight loss and was associated with lower risk of major complications during a 3-year follow-up. But GERD increased in LSG group and decreased in LRYGB group.

Angiotensin II receptor blockers, steroids and radiotherapy in glioblastoma-a randomised multicentre trial (ASTER trial). An ANOCEF study.

BACKGROUND: Glioblastomas (GBMs) induce a peritumoural vasogenic oedema impairing functional status and quality of life. Steroids reduce brain tumour-related oedema but are associated with numerous side-effects. It was reported in a retrospective series that angiotensin receptor blockers might be associated with reduced peritumoural oedema. The ASTER study is a randomised, placebo-controlled trial to assess whether or not the addition of Losartan to standard of care (SOC) can reduce steroid requirement during radiotherapy (RT) in patients with newly diagnosed GBM. PATIENTS AND METHODS: Patients with a histologically confirmed GBM after biopsy or partial surgical resection were randomised between Losartan or placebo in addition to SOC with RT and temozolomide (TMZ). The primary objective was to investigate the steroid dosage required to control brain oedema on the last day of RT in each arm. The secondary outcomes were steroids dosage 1 month after the end of RT, assessment of cerebral oedema on magnetic resonance imaging, tolerance and survival. RESULTS: Seventy-five patients were randomly assigned to receive Losartan (37 patients) or placebo (38 patients). No difference in the steroid dosage required to control brain oedema on the last day of RT, or one month after completion of RT, was seen between both arms. The incidence of adverse events was similar in both arms. Median overall survival was similar in both arms. CONCLUSIONS: Losartan, although well tolerated, does not reduce the steroid requirement in newly diagnosed GBM patients treated with concomitant RT and TMZ. Trial registration number NCT01805453 with ClinicalTrials.gov.

Early screening for gestational diabetes mellitus is not associated with improved pregnancy outcomes: an observational study including 9795 women.

AIMS: In addition to screening for hyperglycaemia during pregnancy after 24 weeks of gestation (WG), the current guidelines also suggest screening in early pregnancy and referring women with early gestational diabetes mellitus (eGDM) or overt diabetes (OD) for immediate care. Our aim was to evaluate this strategy. METHODS: This study evaluated, at our hospital (2012-2016), whether the incidence of a predefined composite outcome (preeclampsia, large-for-gestational-age infant, shoulder dystocia) and secondary outcomes was different when women were screened only after 22WG ('late screening only') or before 22WG and treated for eGDM or OD if present, with repeat screening after 22WG if absent ('early ± late screening'). RESULTS: Early ± late screening (n = 4605, 47.0%) increased between 2012 and 2016 (P < 0.0001) and was associated with more risk factors for GDM than late screening only. Glycaemic status differed in both groups (early ± late screening: eGDM 10.3%, GDM 12.1%, OD 0.9% vs. late screening only: GDM 16.8%, OD 1.2%; P < 0.001), with a higher rate of insulin therapy (8.9% vs. 6.0%; P < 0.001) and less gestational weight gain (11.1 ± 5.4 kg vs. 11.4 ± 5.5 kg; P = 0.013) in the early ± late screening group. Rates of those meeting the composite criterion were similar in both groups [11.6% vs. 12.0%, respectively; odds ratio (OR): 1.040, 95% confidence interval (CI): 0.920-1.176; P = 0.53] and remained comparable after adjusting for Propensity Scores (OR: 1.046, 95% CI: 0.924-1.185; P = 0.4790). Rates for secondary outcomes were also similar in both groups. CONCLUSION: While a strategy including early measurement of fasting plasma glucose during pregnancy increases the incidence and care of hyperglycaemia during pregnancy, it may not significantly improve pregnancy outcomes.

[Hydroxychloroquine to obtain pregnancy without adverse obstetrical events in primary antiphospholipid syndrome: French phase II multicenter randomized trial, HYDROSAPL]. / Évaluation du bénéfice de l'utilisation d'hydroxychloroquine pour l'obtention d'une grossesse à terme non compliquée en cas de syndrome des antiphospholipides primaire : étude de phase II multicentrique randomisée en double insu versus placebo, HYDROSAPL.

Antiphospholipid syndrome is defined by the presence of thrombosis and/or obstetrical adverse events (≥3 recurrent early miscarriage or fetal death or a prematurity<34 weeks of gestation) associated with persistent antiphospholipid antibodies. The pregnancy outcome has been improved by the conventional treatment (aspirin 100mg/day with low molecular weight heparin [LMWH] from 30 to 75% of uncomplicated pregnancies. In PROMISSE study, 19% of pregnancies had at least one obstetrical adverse event despite treatment (maternal, fetal or neonatal complications) in relation with APS. In the European registry of babies born from APS mothers, maternal and foetal adverse events were observed in 13% of cases, with prematurity in 14% despite treatment. The presence of lupus erythematosus, a history of thrombosis, presence of lupus anticoagulant and APL triple positivity are considered as factors associated with unfavorable obstetrical outcome. Hydroxychloroquine (HCQ) has anti-inflammatory and anti-thrombotic properties. Studies in vitro have shown that HCQ is able to restore the placental expression of Annexin V, which has an anticoagulant effect and to prevent the placental injury induced by APL. HCQ used for lupus erythematosus decrease the thrombotic risk and its value for thrombotic APS has been raised in an open labelled French study. In European retrospective study, the addition of HCQ to conventional treatment improved refractory obstetrical APS. Its use during the pregnancy of patients with lupus erythematosus, the evidence of good safety during the pregnancy and follow-up of children born to mothers exposed to HCQ demonstrate an overall good safety profile for mothers and the fetus. This clinical trial is designed to assess the interest of the addition of hydroxychloroquine to conventional treatment in APS during the pregnancy.

Effect of preoxygenation using non-invasive ventilation before intubation on subsequent organ failures in hypoxaemic patients: a randomised clinical trial.

BACKGROUND: Previous data showed that non-invasive ventilation (NIV) applied for 3 min before tracheal intubation ensured better oxygenation compared with using a non-rebreather bag-valve-mask. We aimed to determine whether preoxygenation using NIV is effective in reducing the incidence of organ dysfunction in hypoxaemic, critically ill patients in intensive care. METHODS: A multicentre, randomised, open-label trial evaluating 100% FiO2 administered with NIV (99 patients) vs with face mask (102 patients) for 3 min before tracheal intubation. The primary endpoint was the maximal value of Sequential Organ Failure Assessment score within 7 days after intubation. RESULTS: The median (inter-quartile range) values of the maximal value of the Sequential Organ Failure Assessment score within 7 days post-intubation were not significantly different between the two randomised groups: nine (6-12) in the NIV group vs 10 (6-12) in the face mask group (P=0.65). In patients treated by NIV prior to the randomisation, there was a significant increase in the occurrence in adverse events in patients randomised to face mask [odds ratio=5.23 (1.61;16.99), P=0.0059]. CONCLUSIONS: This study failed to demonstrate any benefits of using NIV as a preoxygenation method to reduce organ dysfunction compared with usual preoxygenation in hypoxaemic, critically ill patients requiring tracheal intubation for invasive ventilation. NIV should not be discontinued for preoxygenation in the cases of patients treated by NIV before the decision to intubate. CLINICAL TRIAL REGISTRATION: NCT00472160.

Outcomes of endoscopic ethmoidectomy performed on a day-case basis: a prospective bi-centric study.

Evaluation of endoscopic ethmoidectomy performed as a day-case in terms of security, quality, and satisfaction of the patient. This prospective observatory bi-centric study over 1 year included 74 patients undergoing an ethmoidectomy respecting the eligibility criteria of ambulatory care. We recorded patients' demographic data, operative details, satisfaction, postoperative course, and follow-up results. Nasal symptoms were evaluated by SNOT-22 on preoperative appointment and postoperatively at D30. No non-absorbable nasal packing was used, eventually in the case of preoperative-bleeding absorbable gelatine packing. The postoperative follow-up took place at D1 by phone call and at D10 and D30 to assess complications, Visual Analogue Scale, and state of ethmoidal corridors by endoscopic exam. Patients benefited of bilateral ethmoidectomy in 82.4 % cases associated with septoplasty in 42 %. The majority (95 %) was discharged on the same day. Only one patient had bleeding at D0 and was kept in standard hospitalization, such as three other patients for medical or organizational reasons not related to surgery. At D1, 23 % described postoperative light bleeding but needed no revisit and pain was estimated at 1.3 (VAS). No readmission was observed, and no major complication was noted. SNOT-22 decreased successfully by 56 %, statistically related to postoperative treatment of corticosteroids and in the case of Samter triad. 97 % of patients were satisfied of the ambulatory care. These results suggest that within an experienced and dedicated day-case medical and paramedical team, ethmoidectomy can be safely performed on a day-case basis with high quality of taking care and satisfaction of patients.

Comparison of scores associating symptoms and rescue medication use for evaluating the efficacy of allergy immunotherapy in seasonal allergic rhinoconjunctivitis: results from five trials.

BACKGROUND: Over the past decade, regulatory bodies and scientific societies recommended, as primary efficacy outcome, a score that reflects both symptom severity and use of rescue medication for clinical trials in allergy immunotherapy (AIT). OBJECTIVE: We sought to compare the results obtained with two subject-specific scores, the Combined Score (CS) and the Adjusted Symptom Score (AdSS), for assessment of AIT in seasonal allergic rhinoconjunctivitis due to birch and grass pollen allergens. METHODS: CS and AdSS were evaluated in subjects receiving a 300IR dose of allergen extract daily, by sublingual route, in four clinical trials with the 5-grass pollen tablet (NCT00367640, NCT00409409, NCT00955825 and NCT00418379) and one with the birch pollen solution (NCT01731249). The CS is derived from the Rhinoconjunctivitis Total Symptom Score (RTSS) and the Rescue Medication Score (RMS) giving equal weight to symptoms and medication use. The AdSS is a symptom score adjusting for rescue medication use. Efficacy end-points were analysed using an analysis of covariance linear model. RESULTS: In all trials, despite the different constructs of the two scores, Combined Score or Adjusted Symptom Score were similarly reduced in the 300IR group compared to the placebo group. Treatment effect was consistently demonstrated with both scores, CS and AdSS, used as either daily scores or average of the daily scores over the pollen season. Minor differences with the same statistical conclusions were observed between the results, leading to the same interpretation. CONCLUSIONS AND CLINICAL RELEVANCE: The two scores, combined and adjusted scores, for evaluation of clinical efficacy of AIT have led to similar results, with similar statistical conclusions and similar interpretation.

Muscle MRI STIR signal intensity and atrophy are correlated to focal lower limb neuropathy severity.

OBJECTIVES: The objective is to determine if muscle MRI is useful for assessing neuropathy severity. METHODS: Clinical, MRI and electromyography (EMG) examinations were performed in 17 patients with focal lower limb neuropathies. MRI Short Tau Inversion Recovery (STIR) signal intensity, amyotrophy, and muscle fatty infiltration measured after T1-weighted image acquisition, EMG spontaneous activity (SA), and maximal voluntary contraction (MVC) were graded using semiquantitative scores and quantitative scores for STIR signal intensity and were correlated to the Medical Research Council (MRC) score for testing muscle strength. Within this population, subgroups were selected according to severity (mild versus severe), duration (subacute versus chronic), and topography (distal versus proximal) of the neuropathy. RESULTS: EMG SA and MVC MRI amyotrophy and quantitative scoring of muscle STIR intensity were correlated with the MRC score. Moreover, MRI amyotrophy was significantly increased in severe, chronic, and proximal neuropathies along with fatty infiltration in chronic lesions. CONCLUSIONS: Muscle MRI atrophy and quantitative evaluation of signal intensity were correlated to MRC score in our study. Semiquantitative evaluation of muscle STIR signal was sensitive enough for detection of topography of the nerve lesion but was not suitable to assess severity. Muscle MRI could support EMG in chronic and proximal neuropathy, which showed poor sensitivity in these patients.