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Research questionsPatients with severe pulmonary hypertension associated with chronic lung disease have a poor prognosis. Targeted-pulmonary arterial hypertension therapies might improve exercise capacity and outcome, but there are no guidelines of treatments which are not recommended because of an unproven benefit, with discordant results from few studies in this context.The aim of our study was to evaluate targeted pulmonary arterial hypertension therapies for severe group 3 pulmonary hypertension patients.Study Design and MethodsWe conducted an observational retrospective monocentre study on patients with severe group 3 pulmonary hypertension diagnosed on right heart catheterization treated with targeted therapies. Primary outcome was an improvement of the distance on 6-minute walk test of at least 30 meters. Secondary endpoints included changes in hemodynamic (pulmonary vascular resistance and mean pulmonary arterial pressure) and identification of potential predictive factors of therapeutic response.Results139 patients were enrolled. Most patients had monotherapy with phosphodiesterase 5 inhibitors (n=128; 92%). Mean change in 6MWD was+1.5 meters after treatment (p=0.59). Forced Expiratory Volume in one second and Forced Vital Capacity were not predictive factors for response. We found a significant improvement of pulmonary vascular resistances and mean pulmonary arterial pressure respectively of −1.0 UI Wood (pConclusionOral targeted-pulmonary arterial hypertension therapies do not improve exercise capacity in patients with severe pulmonary hypertension associated with chronic lung disease but could improve hemodynamic parameters.

Introduction Usually benign, pituitary tumors (PT) can be invasive and aggressive with a propensity to progress and/or recur. Trouillas's clinicopathological classification attempts to predict the evolutionary risk of a PT. In this study, we assessed the prognostic value of this classification in an independent patient cohort and analyzed its impact on treatment strategies. Patients and methods In this study, 607 patients operated on between 2008 and 2018 for a PT were included. Grading was established based on invasion, proliferative activity (Ki-67, mitotic index) and p53 positivity. The therapeutic management following surgery was analyzed. Progression-free survival (PFS) of the graded tumors was estimated (Kaplan–Meier method and log-rank test) and a multivariate analysis was performed (Cox regression model). Results Grading identified non-invasive PT without (grade 1a: 303 cases) or with proliferative activity (grade 1b: 53 cases) and invasive PT without (grade 2a: 202 cases) or with proliferative activity (grade 2b: 49 cases). The mean follow-up was 47 ± 30 months (median: 38 months). Progression/recurrence occurred in 127 cases. Grades were significant and independent predictors of PFS (P Discussion Grading of a PT according to Trouillas's classification predicts its risk of progression and should advocate for a personalized therapeutic approach in invasive and proliferative tumors. Significance statement This is the first study to assess, on a cohort of 607 well-characterized patients, the real-life therapeutic impact of the five-tiered clinicopathological classification of pituitary tumors. First, we validate that pituitary tumor grades predict the evolutionary risk of the tumor, with a significant higher risk of progression/recurrence in invasive and/or proliferative tumors (mean follow-up: 47 ± 30 months, median: 38 months). Moreover, our study provides evidence that patients with proliferative tumors have a higher risk to be retreated after primary surgery and point toward the fact that radiotherapy can successfully control tumor growth in case of progression or recurrence. Our findings advocate for a personalized therapeutic approach in clinically aggressive pituitary tumors.

BackgroundMore than half of infants with complex congenital heart disease (CHD) will have a neurodevelopmental disorder of multifactorial causes. The preoperative period represents a time-window during which neonates with complex CHD are in a state of hypoxia and hemodynamic instability, which fosters the emergence of brain injuries and, thus, affects early brain networks and neurodevelopmental outcomes. Currently, there is no consensus regarding the optimal age for cardiac surgery in terms of neurodevelopmental outcomes, and its definition is a real challenge. Our aim is to determine the relationship between cardiac surgical timing and long-term neurodevelopmental outcomes for various types of complex CHD.MethodsWe hypothesize that earlier surgical timing could represent a neuroprotective strategy that reduces perioperative white matter injuries (WMIs) and postoperative morbidity, leading to improved neurodevelopmental outcomes in infants with complex CHD. Firstly, our prospective study will allow us to determine the correlation between age at the time of surgery (days of life) and neurodevelopmental outcomes at 24 months. We will then analyze the correlation between age at surgery and (i) the incidence of WMIs (through pre- and postoperative MRIs), (ii) postoperative morbidity, and (iii) the duration of the hospital stay.Implications and DisseminationThis research protocol was registered in the Clinical Trial Registry (National Clinical Trial: NCT04733378). This project aims to help launch the first Neurocardiac Investigation Clinic in Marseille — AP-HM — to propose an overall personalized monitoring and treatment program for patients operated on for complex CHD.

Background After a type A aortic dissection repair, a patent false lumen in the descending aorta is the most common situation encountered, and is a well-known risk factor for aortic growth, reinterventions and mortality. The aim of this study was to analyze the long-term results of residual aortic dissection (RAD) at a high-volume aortic center with prospective follow-up. Methods In this prospective single-center study, all patients operated for type A aortic dissection between January 2017 and December 2022 were included. Patients without postoperative computed tomography scans or during follow-up at our center, and patients without RAD were excluded. The primary endpoint was all-cause mortality during follow-up for patients with RAD. The secondary endpoints were perioperative mortality, rate of distal aneurysmal evolution, location of distal aneurysmal evolution, rate of distal reinterventions, outcomes of distal reinterventions, and aortic-related death during follow-up. Results In total, 200 survivors of RAD comprised the study group. After a mean follow-up of 27.2 months (1–66), eight patients (4.0%) died and 107 (53.5%) had an aneurysmal progression. The rate of distal reintervention was 19.5% (39/200), for malperfusion syndrome in seven cases (3.5%) and aneurysmal evolution in 32 cases (16.0%). Most reinterventions occurred during the first 2 years (82.1%). Twenty-seven patients were treated for an aneurysmal evolution of RAD including aortic arch with hybrid repair in 21 cases and branched aortic arch endoprosthesis in six cases. In the hybrid repair group, there was no death, and the rate of morbidity was 28.6% (6/21) (one minor stroke, one pulmonary complication, one recurrent paralysis with complete recovery and three major bleeding events). In the branched endograft group, there was no death, no stroke, and no paraplegia. There was one case (16.7%) of carotid dissection. Complete aortic remodeling or complete FL thrombosis on the thoracic aorta was found in 18 cases (85.7%) and in five cases (83.3%) in the hybrid and branched endograft groups, respectively. Conclusions: Despite a critical course in most cases of RAD, with a high rate of aneurysmal evolution and reintervention, the long-term mortality rate remains low with a close follow-up and a multidisciplinary management in an expert center.

International audience; Background Although the triple positivity of antiphospholipid antibodies (aPL) is important for classifying high-risk patients, interpretation of aPL positivity, namely the lupus anticoagulant (LA), anti-cardiolipin (aCL), and anti-beta2-glycoprotein I autoantibodies (aB2GPI) remains challenging for thrombotic risk stratification. Objective To compare biological and clinical data between triple aPL- and single aCL-positive patients. Methods Of the 6500 patients assayed for aPL in daily practice within 3 years, we retrospectively analyzed data from 161 patients that were either triple aPL-positive or single aCL-positive with 5 years' follow-up for 121 of them. Results Whatever triple or single aPL positivity, we found a high prevalence of "carrier" patients (43%), which led us to question the clinical relevance of the triple aPL positivity. This result also justified the need to identify high-risk profiles. In asymptomatic patients, high risk of thrombotic events is associated with (1) two positive tests for LA or a Rosner Index >27 combined with both aCL-IgG and aB2GPI-IgG positivity, (2) persistent single aCL positivity without an associated autoimmune disease. In symptomatic patients, we demonstrated differences in the phenotype of patients and their therapeutic anticoagulation according to the number of positive aPL but we did not find differences in the number of clinical events, recurrence, or relapse, even in the absence of treatment. Conclusion This study shows that the thrombotic risk does not necessarily increase with the number of positive tests and raises the question of the therapeutic management of single aCL-positive patients.

Place: United States; This study's objective was to correlate the abnormalities in brain MRIs performed at corrected-term age for minor or moderate neurocognitive disorders in children school-age born extremely premature (EPT) and without serious sequelae such as autism, cerebral palsy, mental impairment. Data were issued from a cross-sectional multicenter study (GP-Qol study, number NCT01675726). Clinical examination and psychometric assessments were performed when the children were between 7 and 10 years old during a day-long evaluation. Term-equivalent age brain MRIs on EPT were analyzed with a standardized scoring system. There were 114 children included in the study. The mean age at the time of evaluation, was 8.47 years old (± 0.70). 59% of children with at least one cognitive impairment and 53% who had a dysexecutive disorder. Only ten EPT (8.7%) presented moderate to severe white and grey matter abnormalities. These moderate to severe grey matter abnormalities were associated with at least two abnormal executive functions [OR 3.08 (95% CI 1.04-8.79), p = 0.04] and language delay [OR 3.25 (95% CI 1.03-9.80), p = 0.04]. These results remained significant in the multivariate analysis. Moderate to severe ventricular dilatation abnormalities (15%, n = 17) were associated with ideomotor dyspraxia [OR 7.49 (95% CI 1.48-35.95), p = 0.02] and remained significant in multivariate analysis [OR 11.2 (95% CI 1.45-131.4), p = 0.02]. Biparietal corrected diameters were moderate abnormal in 20% of cases (n = 23) and were associated to visuo spatial integration delay [OR 4.13 (95% CI 1.23-13.63), p = 0.02]. Cerebral MRI at term-equivalent age with scoring system analysis can provide information on long-term neuropsychological outcomes at school-age in EPTs children having no severe disability.

OBJECTIVES The aim of this study was to describe the epidemiology of patients undergoing diagnostic and/or curative surgical pulmonary resections for lung opacities suspected of being localized primary lung cancers without preoperative tissue confirmation. METHODS We performed a single-centre retrospective study of a prospectively implemented institutional database of all patients who underwent pulmonary resection between January 2010 and December 2020. Patients were selected when surgery complied with the Fleischner society guidelines. We performed a multivariable logistic regression to determine the preoperative variables associated with malignancy. RESULTS Among 1392 patients, 213 (15.3%) had a final diagnosis of benignancy. We quantified futile parenchymal resections in 29 (2.1%) patients defined by an anatomical resection of >2 lung segments for benign lesions that did not modified the clinical management. Compared with patients with malignancies, patients with benignancies were younger (57.5 vs 63.9 years, P CONCLUSIONS Futile parenchymal lung resection for suspicious opacities without preoperative tissue diagnosis is rare (2.1%) while surgery for benign lesions represented 15.3% and has a satisfactory safety profile with very low postoperative morbi-mortality.

Health of people with severe haemophilia (PwSH) improves thanks to the advancements in haemophilia care, giving them more opportunities in occupational integration. However, there is little literature on the occupational integration of PwSH.The main objective of our study was to assess the occupational integration of PwSH and to compare it with that of the general population. The secondary objective was to study the association between individual characteristics (sociodemographic, clinical and psycho-behavioural) and occupational integration of PwSH.A multicentre, non-interventional, cross-sectional study was conducted in 2018-2020 on PwSH, aged over 18 and under 65 years and included in the FranceCoag registry. Measurements included indicators of occupational integration, sociodemographic, clinical and psycho-behavioural characteristics. The indicators of occupational integration were compared with those of the general population, using indirect standardization. The data of the general population were available from the National Institute of Statistics and Economic Studies (INSEE). Determinants of occupational integration were explored using structural equation modelling.Of 1262 eligible people, 588 were included. PwSH had a lower employment rate than the general population (standardized ratio, .85; 95% CI, .77-.94). There were more PwSH at tertiary education level than expected (standardized ratio, 1.38; 95% CI, 1.17-1.61). HIV infection, poor physical health and mental health concerns were associated with a higher risk of unemployment in PwSH.Employment rate of PwSH is lower than that of the general population despite their higher education level. Target interventions focusing on determinants of difficult occupational integration could be helpful for PwSH.

Background There are insufficient studies comparing rapid deployment aortic valve replacement (RDAVR) and trans-aortic valve replacement (TAVR) in intermediate-risk patients with severe aortic stenosis (AS). Aims We compared 2-year outcomes between RDAVR with INTUITY and TAVR with SAPIEN 3 in intermediate-risk patients with AS. Methods Inclusion criteria were patients with severe AS at a EuroSCORE II ≥ 4%, who received RDAVR or TAVR implantation and clinical evaluation by the Heart Team. Regression adjustment for the propensity score was used to compare RDAVR and TAVR. Primary outcome was the composite criterion of death, disabling stroke, or rehospitalization. Secondary outcomes major bleeding complications postoperation, paravalvular regurgitation ≥ 2, patient-prosthesis mismatch, and pacemaker implantation. Results A total of 152 patients were included from 2012 to 2018: 48 in the RDAVR group and 104 in the TAVR group. The mean age was 82.7 ± 6.0,51.3% patients were female, the mean EuroSCORE II was 6.03 ± 1.6%, mean baseline LVEF was 56 ± 13%, mean indexed effective orifice area was 0.41 ± 0.1 cm/m2 , and the mean gradient was 51.7 ± 14.7 mmHg. RDAVR patients were younger (79.5 ± 6 years vs. 82.6 ± 6 years; p = .01), and at higher risk (EuroSCORE II, 6.61 ± 1.8% vs. 5.63 ± 1.5%; p = .005), Twenty-two patients (45.99%) in the RDAVR group and 32 (66.67%) in the TAVR group met the composite criterion. Through the 1:1 propensity score matching analysis, there was a significant difference between the groups, favoring RDAVR (HR = 0.58 [95% CI: 0.34-1.00]; p = .04). No differences were observed in terms of patient-prosthesis mismatch (0.83 [0.35-1.94]; p = .67), major bleeding events (1.33 [0.47-3.93]; p = .59), paravalvular regurgitation ≥ 2 (0.33[0-6.28]; p = .46), or pacemaker implantation (0.84 [0.25-2.84]; p = .77) CONCLUSION: RDAVR was associated with better 2-year outcomes than TAVR in intermediate-risk patients with severe symptomatic AS.

Background Laparoscopy is the gold standard approach in numerous surgical procedures. A new generation of robotized instruments has been developed to compensate for the ergonomic constraints of conventional instruments. The main objective was to compare the learning curves of novices for intracorporeal suturing on a laparoscopy pelvitrainer, using either a robotized needle holder or conventional needle holders. The post-training performances under ergonomically difficult conditions were also analyzed. Materials and methods Fifth-year medical students were randomized in group A using a robotized needle holder (JAIMY; Endocontrol, Grenoble, France) and group B using straight conventional needle holders. They undertook four training sessions (intracorporeal knot-tying task) followed by an evaluation session (intracorporeal knots-tying task, frontal suture, and hexagonal suture). Results Twenty participants were included. The performances of the two groups (n = 10) were not significantly different at baseline. During the training sessions, there was a learning curve with a plateau at the third session for both the groups. At the final evaluation session, there was no significant difference between group A and group B for the intracorporeal knot-tying task (median fundamentals of laparoscopic surgery score: 468 versus 474.5 respectively; P = 0.762). There was a significant difference between group A and group B for the frontal suture (median global score: 15.75 versus 3.75 respectively; P = 0.005) but not for the hexagonal suture (median global score: 18 versus 15 respectively; P = 0.284). Conclusions Learning curves were equally fast using the robotized needle holder versus conventional instruments and led to equivalent performances. Under ergonomically difficult conditions, the robotized needle holder provided an advantage relative to conventional instruments.

BACKGROUND Postoperative pulmonary complications are associated with increased morbidity. Identifying patients at higher risk for such complications may allow preemptive treatment. METHODS Patients with an American Society of Anesthesiologists (ASA) score >1 and who were scheduled for major surgery of >2 hours were enrolled in a single-center prospective study. After extubation, lung ultrasound was performed after a median time of 60 minutes by 2 certified anesthesiologists in the postanesthesia care unit after a standardized tracheal extubation. Postoperative pulmonary complications occurring within 8 postoperative days were recorded. The association between lung ultrasound findings and postoperative pulmonary complications was analyzed using logistic regression models. RESULTS Among the 327 patients included, 69 (19%) developed postoperative pulmonary complications. The lung ultrasound score was higher in the patients who developed postoperative pulmonary complications (12 [7-18] vs 8 [4-12]; P < .001). The odds ratio for pulmonary complications in patients who had a pleural effusion detected by lung ultrasound was 3.7 (95% confidence interval, 1.2-11.7). The hospital death rate was also higher in patients with pleural effusions (22% vs 1.3%; P < .001). Patients with pulmonary consolidations on lung ultrasound had a higher risk of postoperative mechanical ventilation (17% vs 5.1%; P = .001). In all patients, the area under the curve for predicting postoperative pulmonary complications was 0.64 (95% confidence interval, 0.57-0.71). CONCLUSIONS When lung ultrasound is performed precociously

Fcγ receptors (FcγRs) interact with the C-reactive protein (CRP) and mediate activation of inflammation-related pathogenic mechanisms affecting cardiovascular health. Our study evaluated whether FcγRIIA and FcγRIIIA profiles are associated with the recurrence of adverse cardiovascular events during the first year after a primary acute coronary syndrome (ACS). The primary endpoint was the recurrence of cardiovascular events (RCE), identified as a composite outcome comprising acute heart failure (AHF) and major adverse cardiovascular events (MACE). We obtained blood samples of 145 ACS patients to measure hsCRP circulating levels, to identify FcγRIIA-131RH rs1801274 and FcγRIIIA-158FV rs396991 polymorphisms, to analyze circulating monocytes and NK cell subsets expressing CD16 and CD32, and to detect serum-mediated FCGR2A-HH activation by luciferase reporter assays. The hsCRP, CD32-expression, and Fc-R mediated activation levels were similar in all patients regardless of their MACE risk. In contrast, the hsCRP levels and the proportion of CD14+ circulating monocytes expressing the CD32 receptor for CRP were significantly higher in the patients who developed AHF. The FCGR2A rs1801274 HH genotype was significantly more common in patients who developed RCE and MACE than in RCE-free patients and associated with an enhanced percentage of circulating CD32+CD14+ monocytes. The FCGR2A-HH genotype was identified as an independent predictor of subsequent RCE (OR, 2.7; p = 0.048; CI, 1.01–7.44) by multivariate analysis. These findings bring preliminary evidence that host FCGR2A genetic variants can influence monocyte CD32 receptor expression and may contribute to the fine-tuning of CD32-driven chronic activating signals that affect the risk of developing RCEs following primary ACS events.

IntroductionPolycystic ovarian syndrome (PCOS) is the most frequent etiology of anovulation, hyperandrogenism and infertility in women. Its pathophysiology remains poorly elucidated. Hyperprolactinemia (hPRL) is common in women of reproductive age and may partially mimic the clinical phenotype of PCOS. The simultaneous finding of both conditions is therefore not rare, however there are conflicting studies on whether a link exists between them.Materials and MethodsWe conducted a retrospective monocentric study between 2015 and 2021 and among women who were referred for possible PCOS, we selected those who met the ESHRE/Rotterdam definition criteria. hPRL was defined as two values above the upper limit of normal with at least one measurement in our centre.ResultsA total of 430 women were selected, of whom 179 met the PCOS criteria. 50 out of 179 patients (27.9%) had at least one elevated value of PRL and 21 (11.7%) had hPRL according to our definition. Among the 21 women of the PCOS/hPRL cohort, 5 (23.8%) had a microprolactinoma and all of them had PRL level ≥ 60 ng/ml. The remaining cases were macroprolactinemia (n=5), iatrogenic hPRL (n=4), primary hypothyroidism (n=1) or unexplained (n=6) despite exhaustive investigations. The metoclopramide test resulted in an increase of basal PRL < 300% in all prolactinomas and ≥ 300% in all the other etiologies.ConclusionhPRL was a common finding in PCOS women, secondary to a microprolactinoma in a quarter of cases. Metoclopramide test performed in women with hPRL below 60 ng/ml appeared as a helpful tool 1) to discriminate pituitary causes from others etiologies, 2) to potentially avoid unnecessary pituitary MRI.

Hemodialysis (HD) patients are at risk for severe COVID-19 and cannot comply with social distancing. SARS-COV2 seroprevalence in French patients and caregivers after the first wave of COVID-19 is unknown. SeroCOVIDial is a prospective study conducted between June and December 2020. SARS-COV2 seroprevalence was evaluated by a rapid serological test (BIOSYNEX) in HD patients and caregivers, and the presence or not of anti-SARS-COV2 neutralizing or non-neutralizing antibodies in patients was also determined by ELISA and seroneutralization. In June 2020, 451 HD patients and 238 caregivers were included. Overall SARS-COV2 seroprevalence was 8.4% (patients) and 6.7% (caregivers), and was 87.1% (patients) and 90.0% (caregivers) in participants with a previously documented SARS-COV2 infection. Overall seroprevalence reached 13.8% (patients) and 12.6% (caregivers) following the second epidemic wave. During the follow-up, 38 (8.4%) patients died (9 of COVID-19). Among the 44 (10.6%) patients who became infected, only two were seropositive at M0. The levels of anti-SARS-COV2 antibodies decreased over time in patients and caregivers. The BIOSYNEX test showed 82.9% sensitivity and 97.7% specificity. Prevalence of anti-SARS-COV2 antibodies was low in HD patients and caregivers after the first epidemic wave but rose after the second wave. A rapid serological test showed good performances and could be useful for future monitoring of anti-SARS-COV2 antibodies.

International audience; School-aged extremely preterm (EPT) children have multiple specific neurocognitive/behavioral disorders that are often associated with other disorders; this manifests a true neurobehavioral “phenotype” of prematurity. To determine a profile of cognitive/behavioral impairments in a population of school-aged EPT children (7–10 years-old) without major disabilities, a cross-sectional study was conducted in five medical centers. An algorithm distributed the study population according to four WISC-IV subtests, five NEPSY-2 subtests, and two variables of figure of Rey. The behavior (SDQ), anxiety (Spielberg STAI-C), and generic QoL (Kidscreen 10 and VSP-A) were also evaluated. The study included 231 school-aged EPT children. Three neurobehavioral “phenotypes” were defined according to their severity: 1 = moderately, 2 = minor, and 3 = unimpaired. In all the profiles, the working memory, perceptual reasoning, as well as mental flexibility, were close to or below average, and their emotional behavior was always troubled. Self-esteem and school-work were the most impacted QoL areas. The unimpaired neurobehavior exhibited emotional behavioral impairment and executive dysfunction. The profile analysis defined distinct outcome groups and provided an informative means of identifying factors related to developmental outcomes. The QoL deterioration is determined by the severity of the three neurobehavioral “phenotypes”, which is defined as well as by dysexecutive and/or behavioral disorders.

Benzo(a)pyrene (BaP) is a recognized reprotoxic compound and the most widely investigated polycyclic aromatic hydrocarbon in ambient air, it is widespread by the incomplete combustion of fossil fuels along with cerium dioxide nanomaterials (CeO2 NMs), which are used in nano-based diesel additives to decrease the emission of toxic compounds and to increase fuel economy. The toxicity of CeO2 NMs on reproductive organs and cells has also been shown. However, the effect of the combined interactions of BaP and CeO2 NMs on reproduction has not been investigated. Herein, human and rat gametes were exposed in vitro to combusted CeO2 NMs or BaP or CeO2 NMs and BaP in combination. CeO2 NMs were burned at 850 °C prior to mimicking their release after combustion in a diesel engine. We demonstrated significantly higher amounts of DNA damage after exposure to combusted CeO2 NMs (1 µg·L−1) or BaP (1.13 µmol·L−1) in all cell types considered compared to unexposed cells. Co-exposure to the CeO2 NMs-BaP mixture induced additive DNA damage in sperm and cumulus cells, whereas no additive effect was observed in rat oocytes. This result could be related to the structural protection of the oocyte by cumulus cells and to the oocyte’s efficient system to repair DNA damage compared to that of cumulus and sperm cells.

Background QTc interval monitoring, for the prevention of drug-induced arrhythmias is necessary, especially in the context of coronavirus disease 2019 (COVID-19). For the provision of widespread use, surrogates for 12‑lead ECG QTc assessment may be useful. This prospective observational study compared QTc duration assessed by artificial intelligence (AI-QTc) (Cardiologs®, Paris, France) on smartwatch single‑lead electrocardiograms (SW-ECGs) with those measured on 12‑lead ECGs, in patients with early stage COVID-19 treated with a hydroxychloroquine−azithromycin regimen. Methods Consecutive patients with COVID-19 who needed hydroxychloroquine−azithromycin therapy, received a smartwatch (Withings Move ECG®, Withings, France). At baseline, day-6 and day-10, a 12‑lead ECG was recorded, and a SW-ECG was transmitted thereafter. Throughout the drug regimen, a SW-ECG was transmitted every morning at rest. Agreement between manual QTc measurement on a 12‑lead ECG and AI-QTc on the corresponding SW-ECG was assessed by the Bland-Altman method. Results 85 patients (30 men, mean age 38.3 ± 12.2 years) were included in the study. Fair agreement between manual and AI-QTc values was observed, particularly at day-10, where the delay between the 12‑lead ECG and the SW-ECG was the shortest (−2.6 ± 64.7 min): 407 ± 26 ms on the 12‑lead ECG vs 407 ± 22 ms on SW-ECG, bias −1 ms, limits of agreement −46 ms to +45 ms; the difference between the two measures was, Highlights • Artificial intelligence fairly interpreted QTc • Single lead smartwatch ECG is an option for home monitoring ECG • Because of social distancing necessity with COVID-19, home monitoring ECG is crucial.

International audience; Background: The detection of additional autoantibodies is of great concern in systemic sclerosis (SSc) when those included in the ACR/EULAR classification are negative. In this context, the interest of antifibrillarin (anti-U3RNP) autoantibodies (AFAs) in the routine evaluation of SSc remains unclear. We aimed to assess the relevance of AFAs and their clinical association in SSc patients. Methods: In a multicenter observational retrospective study, we collected immunological and clinical data associated with AFA positivity in SSc (n = 42) and non-SSc patients (n = 13). Patients with SSc negative for AFAs (n = 83) were considered as a control group. AFAs were detected by indirect immunofluorescence (IIF) using HEp-2 cells, EliA or immunoblot techniques. Results: We confirmed a typical nuclear IIF pattern and showed that AFAs are mostly exclusive towards SSc conventional autoantibodies. Although also observed in non-SSc patients, high levels of AFAs with the ELiA technique allowed the diagnosis of SSc. Compared to AFA-negative SSc patients, AFA-positive SSc patients more frequently exhibited visceral involvements. They more frequently suffered from the diffuse cutaneous form and had a higher global severity of the disease. Conclusions: We demonstrate the usefulness of quantifying AFAs in the immunological exploration of SSc, especially when patients are seronegative for SSc conventional autoantibodies and display a typical IIF pattern. AFAs might constitute an interesting marker of SSc severity.

International audience; Objective: To develop a modified version of Objective Structured Assessment of Technical Skill (OSATS) rating scale for evaluation of surgical skills specific to caesarean and to assess its relevance in documenting the residents’ learning curve during their training. Secondarily, to verify the scale’s stability to caesarean’s level of difficulty and comparing self-assessment to hetero-assessment in order to propose a practical application of this rating scale during residency.Study Design: We conducted a multicentre observational prospective study, from May 2018 to November 2018. All residents at that time could participate and fill in the rating scale after caesarean. Senior surgeons had to fill in the same rating scale. We analysed correlation between self-assessments and hetero-assessments and sensitivity to change of the rating scale. Analysis of feature’s relevance was performed by principal component analysis, factor analysis and reliability analysis.Results: In total, 234 rating scales were completed evaluating 18 residents. Our study demonstrated that our rating scale could be used to evaluate surgical skills of residents during caesarean and distinguish their year of residency (p < 0.001) with a high correlation between self and hetero-assessment (Intraclass Correlation coefficient for global score: 0.78; 95% CI 0.68−0.86). The principal component analysis revealed two dimensions corresponding to the two parts of the rating scale and the factorial analysis allowed us to confirm distribution of features according to these two dimensions. Cronbach’s alpha allowed us to highlight the percentage of representation of the scale’s features in relation to all potential theoretical features (0.93, 95% CI 0.82−0.95).Conclusion: Our rating scale could be used for self-assessment during residency and as a hetero-assessment tool for validating defined stages of the internship.

International audience; Although bicuspid aortic valve (BAV) is one of the most common congenital heart diseases, clinical data associated with valve dysfunction are still limited. We evaluated clinical characteristics and echocardiography of French patients with BAV associated with leaking and stenosis degeneration. We initiated a prospective registry from 2014 to 2018 at a tertiary center. A total of 223 patients (168 males [75%], age 53 ± 17 years) were enrolled. Among these patients 83% had left–right coronary cusps fusion, 80% Sievers type 1 BAV and 49% showed aortic dilatation. Twenty-four patients (11%) had normal valve function, 66 patients (31%) had aortic stenosis (AS), 91 patients (41%) had aortic regurgitation (AR) and 40 patients (17%) had AR and AS. BAV phenotype did not predict neither AS nor AR (all p > 0.1). By multivariable analysis, age > 50 (41.6[10.3–248.2], p

Place: Ireland; International audience; OBJECTIVE: More than half of extremely preterm infants are delivered by cesarean section. Few data are available about severe maternal morbidity (SMM) of these extremely preterm cesarean. The objective was to determine whether gestational age under 26 weeks of gestation (weeks) was associated with an increased risk of SMM compared with gestational age between 26 and 34 weeks in women having a cesarean delivery. MATERIAL AND METHODS: We searched MEDLINE, ISI Web of Science, the Cochrane Database, PROSPERO, and ClinicalTrials.gov on January 31, 2020. The search strategy clustered terms describing SMM and preterm cesarean delivery. No restrictions on language, publication status, and study design were applied. Abstracts were included if there was sufficient information to assess study quality. The authors of all identified studies were contacted to request for aggregated data. Relative risks (RR) were calculated using the inverse variance method. The primary outcome was SMM as defined in each study. We analyzed data on preterm cesarean deliveries between 22 and 34 weeks. The protocol was registered in PROSPERO (registration: CRD42019128644). RESULTS: Six studies involving 45,572 women (3,440 delivering \textless 26 weeks; 42,132 delivering between 26 and 34 weeks) were included. SMM occurred in 607 women (17.6 %) \textless 26 weeks and 4,483 women (10.6 %) between 26 and 34 weeks. Gestational age \textless 26 weeks was associated with an increased risk of SMM (RR, 1.65; 95 % CI [Confidence Interval], 1.52-1.78; I(2) = 40 %). Gestational age \textless 26 weeks remained associated with SMM in the subgroup analyses depending on the type of the study (prospective or retrospective), country of the study (European or non-European), and high quality of the study. A sensitivity analysis showed that gestational age \textless 25 weeks was also associated with SMM in preterm cesarean delivery (RR, 1.66; 95 % CI, 1.50-1.83; I(2) = 3%). CONCLUSIONS: Gestational age \textless 26 weeks was associated with an increased risk of SMM in women having a preterm cesarean delivery. Obstetricians and neonatologists should be aware of the increased risk of SMM in cesarean.

Sevoflurane, a volatile anesthetic, is used when extremely preterm neonates (EPT) undergo painful procedures. Currently, no existing studies analyze sevoflurane’s long-term effects during the EPT’s immediate neonatal period. Our primary objective was to compare the EPT’s neurocognitive development regardless of any sevoflurane exposure prior to 45 weeks corrected gestational age (GA). We analyzed those live discharges, less than 28 weeks GA, who were either exposed, unexposed, and/or multiply exposed to sevoflurane before 45 weeks GA. All data were obtained from a cross-sectional multicenter study (GPQoL study, NCT01675726). Children, both exposed and non-exposed to sevoflurane, were sampled using a propensity-guided approach. Neurological examinations (Touwen), cognitive and executive functions (WISC IV, NEPSY, Rey figure), and assessments when the children were between 7 and 10 years old, were correlated to their neonatal sevoflurane exposure. There were 139 children in the study. The mean gestational age was 26.2 weeks (±0.8) GA and the mean birth weight was 898 g (±173). The mean age of their evaluation was 8.47 years old (±0.70). Exposure to sevoflurane to the mean corrected age 27.10 (3.37) weeks GA had a significant correlation with cerebral palsy (adjusted odds ratio (aOR): 6.70 (CI 95%: 1.84–32.11)) and other major disorders (cerebral palsy and/or severe cognitive retardation) (aOR: 2.81 [95% CI: 1.13–7.35]). Our results demonstrate the possibility of long-term effects on EPT infants who had a sevoflurane exposure before 45 weeks corrected GA. However, these results will require further confirmation by randomized controlled trials.

Objective To investigate the determinants of quality of life (QoL) in children with inborn errors of metabolism with restricted diet (IEMRDs) using a single theory-based multidimensional model. Study design In this multicenter cross-sectional study, data from children with IEMRDs (except phenylketonuria) aged 8 to 17 years and their parents were collected from January 2015 to December 2017. Measurements included a child’s self-reported QoL, self-rated behavioral problems and anxiety, and parental anxiety. Based on hypotheses from a literature-built theoretical model linking demographic, clinical, family environment and psychosocial characteristics to QoL either directly or indirectly, associations of these factors with a child's self-rated QoL were examined using a structural equation modeling (SEM) approach. Results A total of 312 children (mean [SD] age, 12.2 [2.6] years; 160 [51%] boys) were included. Higher trait anxiety and behavioral problems in children were the most important factors associated with poorer QoL (standardized path coefficients = −0.71 and −0.23, respectively). Additionally, higher parent trait anxiety, younger age at diagnosis, and having a disease requiring an emergency diet were associated with poorer QoL in these children. The final model fit the data closely according to conventional goodness-of-fit statistics and explained 86% of QoL variance. Conclusions Psychosocial factors appear to be major determinants of QoL impairment in children with IEMRDs. These factors should be particularly addressed in clinical practice as part of the global treatment plan for a child with IEMRD. Future studies based on longitudinal design should consider coping strategies when exploring potential predictive factors of QoL.

Cerium dioxide nanomaterials (CeO2 NMs) are widely used in nano-based diesel additives to decrease the emission of toxic compounds, but they have been shown to increase the emission of ultrafine particles as well as the amount of released Ce. The Organization for Economic Cooperation and Development included CeO2 NMs in the priority list of nanomaterials that require urgent evaluation, and the potential hazard of aged CeO2 NM exposure remains unexplored. Herein, human and rat sperm cells were exposed in vitro to a CeO2 NM-based diesel additive (called EnviroxTM), burned at 850 &deg, C to mimic its release after combustion in a diesel engine. We demonstrated significant DNA damage after in vitro exposure to the lowest tested concentration (1 &micro, g&middot, L&minus, 1) using the alkaline comet assay (ACA). We also showed a significant increase in oxidative stress in human sperm after in vitro exposure to 1 &micro, 1 aged CeO2 NMs evaluated by the H2DCF-DA probe. Electron microscopy showed no internalization of aged CeO2 NMs in human sperm but an affinity for the head plasma membrane. The results obtained in this study provide some insight on the complex cellular mechanisms by which aged CeO2 NMs could exert in vitro biological effects on human spermatozoa and generate ROS.

Background: There is insufficient evidence regarding the comparison of Rapid Deployment aortic valve replacement(RDAVR) to TAVR in intermediate-risk patients with severe symptomatic aortic stenosis(AS) Aims: We compare the 2-years outcomes between RDAVR with INTUITY and TAVR with SAPIEN 3 in intermediate-risk patients with AS. Methods: Inclusion criteria: severe AS implanted with RDAVR or TAVR; EUROSCORE II ≥ 4% and clinical evaluation by Heart Team. Regression adjustment for the propensity score was used to compare RDAVR with TAVR(1:1). Primary endpoint: composite criterion of death, disabling stroke or rehospitalization. Secondary endpoints: occurrence of major bleeding post-operative complications, paravalvular regurgitation (PVR)≥2 and patient-prosthesis mismatch(PPM) at 1 month and pacemaker implantation at 2 years. Results: A total of 152 patients were included from 2012 to 2018: 48 in the RDAVR group and 104 in the TAVR group. Mean age was 82.7±6, 51.3% were female, mean Euroscore II was 6.03±1.6% and mean baseline LVEF was 56±13%,mean indexed iEOA was 0.41±0.1cm/m2, mean gradient was 51.7±14.7mmHg. Patients with RDAVR were younger(79.5±6vs82.6±6,p=0.01), at higher risk (EUROSCORE2 6,61±1,8%vs5,63±1,5%, p=0.005), combined surgery was performed in 28 patients(58.3%). Twenty-two patients(45.99%) met the primary outcome in the RDAVR group and 32 patients(66.67%) in the TAVR group. By 1:1propensity score matching analysis, there was a significant difference between both groups in favor of RDAVR(HR=0.58[95%CI:0.34;1.00],p=0.04). No difference were observed in PPM occurrence(0.83;[0.35-1.94];p=0.67),major bleeding events(1.33;[0.47-3.93];p=0.59),PVR≥2(0.33[0-6.28],p=0.46), and pacemaker implantation (0.84[0.25-2.84],p=0.77).Conclusion: RDAVR is associated with better 2-years outcomes than TAVR in intermediate-risk patients with severe symptomatic AS.

Background We examined how specific cognitive behavioral impairments impacted quality of life (QoL) within a large multicenter cohort of 7-10 year olds surviving extremely preterm (EPT) without major neurodevelopmental disability. Methods Between 7 and 10 years of age, two generic, self-proxy, and parental evaluations were obtained. QoL measurement questionnaires (Kidscreen-10/VSPA (Vecu et Sante Percue de l'Enfant et de l'Adolescent)) were used and compared to a reference population. The general and specific cognitive functions, such as executive functions, behavior and anxiety, and clinical neurologic examination, were also assessed. Results We analyzed 211 school-aged EPT children. The mean gestational age was 26.2 (±0.8) weeks, birth weight was 879 g (±181) and the mean age was 8.4 years (±0.87). Children with a Full-Scale Index Quotient ≥89, who were considered as normal, had a lower QoL. Specific cognitive impairments: comprehensive language delay, visuo-spatial integration defect, and dysexecutive disorders) were the QoL correlates in the domains of school performance and body image. Conclusions School and health care professionals need to increase their focus on EPT children's lower so as to recognize the preterm behavioral/cognitive phenotype and their potential need for supportive measures. Research on preventive interventions is warranted to investigate if these long-term effects of an EPT birth can be attenuated in neonatal period and after.

Summary Background The incremental prognostic value of left atrial (LA) dysfunction, emerging in various clinical contexts, remains poorly explored in hypertrophic cardiomyopathy (HCM). Objective To assess LA strain correlation with outcome in HCM. Methods A cohort of all 307 consecutive patients presenting with HCM between 2007 and 2017 (54 ± 17 years; 34% women), with comprehensive echocardiography at diagnosis and LA peak longitudinal strain (PALS) and LA peak contraction strain (PACS) measurement, was enrolled and occurrence of HCM related cardiac events analysed. Results Clinically, atrial fibrillation (AF) was present in 13%, New York Heart Association functional class II–III in 54%, and B-type natriuretic peptide (BNP) concentration was 199 ± 278 pg/mL. By echocardiography, left ventricular (LV) ejection fraction (EF) was 67 ± 10%, LV thickness 21 ± 5 mm and European Society of Cardiology HCM risk score 3 ± 3%, with 109 patients (36%) presenting obstructive HCM (LV outflow gradient 21 ± 32 mmHg). LA diameter was 41 ± 8 mm [with 109 (36%) presenting LA diameter ≥ 40 mm], LA volume index 50 ± 26 mL/m2, PALS 24 ± 13%, PACS 11 ± 7% and LA peak systolic strain rate (LASRs) 1.7 ± 0.6 s−1. In addition to AF, age, BNP, LVEF and LV thickness were all independent determinants of lower PALS, with odd ratios almost unchanged after adjustment (all P ≤ 0.0004). At a mean follow-up of 21 (range 18–23) months, patients with adverse cardiac events (n = 65) presented with more impaired LA function (all P ≤ 0.0005), with a significant association between impaired PALS and worse outcome, hazard ratio 0.94 [95% confidence interval (CI) 0.92–0.97, P Conclusions The present study, by gathering a unique HCM cohort, suggests a strong link between LA dysfunction and poor outcome, to be further investigated.

ObjectiveTo examine the impact of ethanol sclerotherapy (EST) for endometrioma on in vitro fertilization (IVF) cumulative live birth rates (CLBR) in women with moderate-severe endometriosis.MethodsThis retrospective cohort study included women with moderate-severe endometriosis (revised American Fertility Society stage III-IV) and endometrioma who underwent IVF with the ultra-long agonist protocol. We compared two groups: women undergoing EST for endometrioma before IVF (EST group), and women whose endometrioma was left in situ during IVF (No-EST group). The primary outcome was the CLBR per IVF cycle, including fresh and frozen embryo transfers. The secondary endpoints included the complication rate, number of mature oocytes retrieved, clinical pregnancy rate and pregnancy loss rate.ResultsSeventy-four women were included in the study, with 37 in the EST group and 37 in the No-EST group, representing 67 and 69 IVF cycles, respectively. The population and cycle characteristics were comparable between the two groups, especially the ovarian response to stimulation. The CLBR was significantly increased in the EST group compared to the No-EST group (31.3% vs. 14.5%, p = 0.03). The clinical and biochemical pregnancy rates were significantly increased in the EST group (37.3% vs. 15.9%, p = 0.01 and 43.3% vs. 23.2%, p = 0.01, respectively). Multivariate analysis revealed a significantly increased chance of live birth in women exposed to EST before IVF with an adjusted OR of 2.68 (95% confidence interval, CI: 1.13-6.36, p = 0.02). In the EST group, we reported one major complication Clavien and Dindo classification grade III, complication involving an ovarian abscess that required a laparoscopic drainage.ConclusionsEST is an interesting technique to improve IVF success rates in women with moderate-severe endometriosis. EST could be discussed before IVF in infertile women.

Research question Is polycyclic aromatic hydrocarbon (PAH) exposure associated with the reproductive outcomes of IVF treatment? Design A prospective, small-scale monocentric cohort study of couples who underwent IVF treatment between January 2018 and June 2019. Both members of each couple answered a questionnaire on PAH exposure and provided urine samples to measure urinary 1-hydroxypyrene (1-OHP) the day before oocyte retrieval and semen collection for fertilization. To assess the specific PAH exposure of gamete cells, immunostaining was conducted on both spermatozoa and granulosa cells obtained during IVF with an anti-benzo(a)pyrene diol epoxide (BPDE) monoclonal antibody that recognizes BDPE-DNA adducts. To assess DNA damage, a comet assay on spermatozoa was conducted. The PAH exposure was compared between couples who had positive HCG and couples who had negative HCG on day 14 after embryo transfer. Results Eighteen couples were included. The mean 1-OHP level in women whose HCG tests were positive (n = 6) was significantly lower than that in women with negative HCG tests (0.098 [0.042–0.170] versus 0.177 [0.067–0.812] μg/g creatinine; P = 0.048). The presence of BPDE-DNA adducts in granulosa cells of women with a negative (29.7 [16.2–57.5] arbitrary units) or positive HCG test (20.3 [9.3–23.3] arbitrary units) were not significantly different (P = 0.092). The urinary 1-OHP levels of men and BPDE-DNA adducts in spermatozoa showed no differences between groups. Conclusions This exploratory research should encourage further studies to determine the effect of women's exposure to PAHs on reproductive outcomes of IVF treatment.

The prognosis of patients with pancreatic cancer remains poor and novel therapeutic targets are required urgently. Treatment resistance could be due to the tumour microenvironment, a desmoplastic stroma consisting of cancer-associated fibroblasts and tumour-infiltrating lymphocytes (TILs). The aim of the study was to evaluate the prognostic value of TILs and cancer-associated fibroblasts (CAFs) in pancreatic cancer of the body and tail.Using tissue microarray from resected left-sided pancreatic cancer specimens, the immunohistochemistry of TILs (cluster of differentiation (CD) 45, CD3, CD4, FoxP3 and CD8), CAFs (vimentin and α-smooth muscle actin (αSMA)) and functional markers (PD-L1 and Ki-67) was examined, and the association with disease-free (DFS) and overall (OS) survival investigated using a computer-assisted quantitative analysis. Patients were classified into two groups, with low or high levels or ratios, using the 75th percentile value as the cut-off.Forty-three patients were included in the study. Their median DFS and OS were 9 and 27 months respectively. A high CD4/CD3 lymphocyte ratio was associated with poorer DFS (8 months versus 11 months for a low ratio) (hazard ratio (HR) 2·23, 95 per cent c.i. 1·04 to 4·61; P = 0·041) and OS (13 versus 27 months respectively) (HR 2·62, 1·11 to 5·88; P = 0·028). A low αSMA/vimentin ratio together with a high CD4/CD3 ratio was correlated with poorer outcomes. No significant association was found between Ki-67, PD-L1 and survival.In patients with resected left-sided pancreatic cancer, a tumour microenvironment characterized by a high CD4/CD3 lymphocyte ratio along with a low αSMA/vimentin ratio is correlated with poorer survival.El pronóstico del cáncer de páncreas sigue siendo malo y se requieren nuevas dianas terapéuticas de forma urgente. La resistencia al tratamiento podría ser atribuida al microambiente tumoral, un estroma desmoplásico compuesto por fibroblastos asociados al cáncer y linfocitos infiltrantes de tumor. El objetivo del estudio fue evaluar el valor pronóstico de los linfocitos infiltrantes de tumor y de los fibroblastos asociados al cáncer en el cáncer de cuerpo y cola de páncreas. MÉTODOS: Utilizando microarray para el análisis de muestras de tejido obtenidas tras la resección de cáncer de páncreas del lado izquierdo, se realizó inmunohistoquímica de linfocitos infiltrantes de tumor (CD45, CD3, CD4, FoxP3 y CD8), fibroblastos asociados al cáncer (vimentina y actina del músculo liso alfa (αSMA)) y marcadores funcionales (PD-L1 y Ki67), y se investigó la asociación con la supervivencia libre de enfermedad y la supervivencia global. Los resultados se obtuvieron tras un análisis cuantitativo asistido por ordenador. Los pacientes se clasificaron en dos grupos, de bajo y alto riesgo, utilizando el valor del percentil 75 como punto de corte.Se incluyeron 43 pacientes en el estudio. En esta población, la mediana de supervivencia libre de enfermedad y de supervivencia global fueron 9 meses y 27 meses, respectivamente. Una alta proporción de linfocitos CD4/CD3 se asoció a peor supervivencia libre de enfermedad (8 meses versus 11 meses; cociente de riesgos instantáneos, hazard ratio, HR 2,2; i.c. del 95% 1,0-4,6; P = 0,041) y supervivencia global (13 meses versus 27 meses; HR 2,6; i.c. del 95% 1,1-5,9; P = 0.028). Una baja proporción αSMA/vimentina junto con una alta proporción CD4/CD3 se correlacionó con peores resultados. No se encontró asociación significativa entre Ki67, PD-L1 y la supervivencia. CONCLUSIÓN: En pacientes con cáncer de páncreas izquierdo resecado, un microambiente tumoral caracterizado por una alta proporción de linfocitos CD4/CD3 junto con una baja proporción de αSMA/vimentina se correlaciona con una peor supervivencia.

Objective To describe the health status of young patients affected by inborn errors of metabolism that require adherence to a restricted diet (IEMRDs) and to describe and compare their self- and proxy (parent)-reported quality of life (QoL) with reference values. Study design A cross-sectional study was conducted in 2015-2017 in patients affected by IEMRDs (except phenylketonuria) younger than 18 years. Data collection was based on medical records, clinical examinations, parents' and children's interviews, and self-reported questionnaires. Measurements included clinical and healthcare data, child and family environment data, and self- and proxy (parent)-reported QoL. Results Of the 633 eligible participants, 578 were recruited (50.3% boys; mean age: 8.7 years); their anthropometric status did not differ from the general population. Approximately one-half of them had at least 1 complication of the disease. Their self-reported global QoL did not differ from that of the general population. However, relations with friends and leisure activities QoL domains were negatively impacted, whereas relations with medical staff, relations with parents, and self-esteem QoL domains were positively impacted. Their proxy (parent)-reported QoL was negatively impacted. Conclusions Young patients affected by IEMRDs present a high rate of clinical complications. Although their proxy (parent)-reported QoL was negatively impacted, their self-reported QoL was variably impacted (both positively and negatively). These results may inform counseling for those who care for affected patients and their families.

International audience; Background. - Little is known about the effect of prosthesis-patient mismatch (PPM) on out-comes after transcatheter aortic valve replacement. We reported previously an increased risk of PPM with the SAPIEN 3 transcatheter heart valve (S3-THV).Aims. - To investigate the association of PPM with 1-year outcomes in patients with severe aortic stenosis (AS) implanted with S3-THV.Methods. - Moderate PPM was defined by an indexed effective orifice area (iEOA) < 0.85 cm(2)/m(2), and severe PPM by an iEOA < 0.65 cm(2)/m(2). Inclusion criteria were severe symptomatic AS and implantation with S3-THV. The primary endpoint was hospitalization for congestive heart failure (CHF) at 1 year; the secondary endpoint was all-cause mortality.Results. - A total of 208 consecutive patients were included between 2016 and 2018. Male sex was prevalent (53.8%), mean age was 81.9 +/- 6.2 years, mean EuroSCORE II was 4.35 +/- 3.37, mean LVEF was 57.9 +/- 13%. Moderate and severe PPM were observed in 69 (33.2%) and 10 (4.8%) patients. Patients with PPM were younger (80.4 +/- 7 vs 82.8 +/- 5.41 years; P=0.006), had a larger BSA (1.84 +/- 0.19 vs 1.77 +/- 0.19 m(2); P=0.01), a lower iEOA (0.73 +/- 0.08 vs 1.11 +/- 0.22 cm(2)/m(2); P= 2/4 (HR > 100, 95%CI > 100 to > 1000; P< 0.01). PPM did not correlate with alt-cause mortality (HR 0.90, 95%CI 0.22 to 3.03; P=0.86).

Objective: Impaired vascular tone plays an important role in cardiogenic shock. Doppler echocardiography provides a non-invasive estimation of systemic vascular resistance. The aim of the present study was to compare Doppler echocardiography with the transpulmonary thermodilution method for the assessment of systemic vascular resistance in patients with cardiogenic shock. Methods: This prospective monocentric comparison study was conducted in a single cardiology intensive care unit (Hopital Nord, Marseille, France). We assessed the systemic vascular resistance index by both echocardiography and transpulmonary thermodilution in 28 patients admitted for cardiogenic shock, on admission and after the introduction of an inotrope or vasopressor treatment. Results: A total of 35 paired echocardiographic and transpulmonary thermodilution estimations of the systemic vascular resistance index were compared. Echocardiography values ranged from 1309 to 3526 dynes.s.m2/cm5 and transpulmonary thermodilution values ranged from 1320 to 3901 dynes.s.m2/cm5. A statistically significant correlation was found between echocardiography and transpulmonary thermodilution ( r=0.86, 95% confidence interval (CI) 0.74, 0.93; P2/cm5 (95% CI −230.06, 6.16). Limits of agreement were −785.86, 561.96. Conclusions: Doppler echocardiography constitutes an accurate non-invasive alternative to transpulmonary thermodilution to provide an estimation of systemic vascular resistance in patients with cardiogenic shock.

Objective: To compare the short- and mid-term outcomes of preterm twins by chorionicity of pregnancy. Design: Prospective nationwide population-based EPIPAGE-2 cohort study. Setting: 546 maternity units in France, between March and December 2011. Population: A total of 1700 twin neonates born between 24 and 34 weeks of gestation. Methods: The association of chorionicity with outcomes was analysed using multivariate regression models. Main outcome measures: First, survival at 2-year corrected age with or without neurosensory impairment, and second, perinatal, short-, and mid-term outcomes (survival at discharge, survival at discharge without severe morbidity) were described and compared by chorionicity. Results: In the EPIPAGE 2 cohort, 1700 preterm births were included (850 twin pregnancies). In all, 1220 (71.8%) were from dichorionic (DC) pregnancies and 480 from monochorionic (MC) pregnancies. MC pregnancies had three times more medical terminations than DC pregnancies (1.67 versus 0.51%, P < 0.001), whereas there were three times more stillbirths in MC than in DC pregnancies (10.09 versus 3.78%, P < 0.001). Both twins were alive at birth in 86.6% of DC pregnancies compared with 80.0% among MC pregnancies (P = 0.008). No significant difference according to chorionicity was found regarding neonatal deaths and morbidities. Likewise, for children born earlier than 32 weeks, the 2-year follow-up neurodevelopmental results were not significantly different between DC and MC twins. Conclusions: This study confirms that MC pregnancies have a higher risk of adverse outcomes. However, the outcomes among preterm twins admitted to neonatal intensive care units are similar irrespective of chorionicity. EPIPAGE-2 was funded by the French Institute of Public Health Research/Institute of Public Health and its partners: the French Health Ministry, the National Institute of Health and Medical Research (INSERM), the National Institute of Cancer, and the National Solidarity Fund for Autonomy (CNSA); the National Research Agency through the French EQUIPEX programme of investments for the future (reference ANR-11-EQPX-0038); and the PREMUP Foundation. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

The pathophysiology of cardiogenic shock (CS) varies depending on its etiology, which may lead to different hemodynamic profiles (HP) and may help tailor therapy. We aimed to assess the HP of CS patients according to their etiologies of acute myocardial infarction (AMI) and acute decompensated chronic heart failure (ADCHF). We included patients admitted for CS secondary to ADCHF and AMI. HP were measured before the administration of any inotrope or vasopressor. Systemic Vascular Resistances index (SVRi), Cardiac Index (CI), and Cardiac Power Index (CPI) were measured by trans-thoracic Doppler echocardiography on admission. Among 37 CS patients, 28 had CS secondary to ADCHF or AMI and were prospectively included. The two groups were similar in terms of demographic data and shock severity criteria. AMI CS was associated with lower SVRi compared to CS related to ADCHF: 2010 (interquartile range (IQR): 1895&ndash, 2277) vs. 2622 (2264&ndash, 2993) dynes-s&middot, cm&minus, 5&middot, m&minus, 2 (p = 0.002). A trend toward a higher CI was observed: respectively 2.13 (1.88&ndash, 2.18) vs. 1.78 (1.65&ndash, 1.96) L&middot, min&minus, 1&middot, 2 (p = 0.067) in AMICS compared to ADCHF. CS patients had different HP according to their etiologies. AMICS had lower SVR and tended to have a higher CI compared to ADHF CS. These differences should be taken into account for patient selection in future research.

International audience; The detection of anti-phosphatidylethanolamine autoantibodies (aPEs) has been proposed to improve the diagnosis and management of patients presenting clinical manifestations of antiphospholipid syndrome (APS), such as thrombosis, and who are persistently negative for conventional markers. After selecting the most specific ELISA for their detection, we evidenced the interest of aPEs in the exploration of thrombosis when APS conventional markers were negative through a 1-year retrospective study including 1131 consecutive patients routinely tested for aPEs. To validate this result, we assessed aPEs in a newly selected population of 77 patients with unexplained deep vein thrombosis (DVT). With a total prevalence of 19.5%, we confirmed the interest of aPE detection in patients with unexplained DVT who were devoid of other aPLs markers. Since endosomal compartment, a source of ROS production, has been recently identified as the cellular target of aPEs in vitro, we then investigated an association between aPE positivity and reactive oxygen species (ROS) production by measuring the production of thiobarbituric acid-reactive substances. We showed, for the first time, a significant association between aPE positivity and systemic ROS production in patients which led us to hypothesize a new mechanism of action of aPEs in thrombosis through a signaling related to oxidative stress.

Objectives: This study sought to describe the current practices and compare outcomes according to the use of balloon aortic valvuloplasty (BAV) or not during transcatheter aortic valve repl...

International audience; BACKGROUND:Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Guidelines recommend reconsidering surgery when this access is not feasible. However, alternative peripheral accesses exist, although they have not been accurately compared with femoral access.OBJECTIVES:This study compared nonfemoral peripheral (n-FP) TAVR with femoral TAVR.METHODS:Using the data from the national prospective French registry (FRANCE TAVI [French Transcatheter Aortic Valve Implantation]), this study compared the characteristics and outcomes of TAVR procedures according to whether they were performed through a femoral or a n-FP access, using a pre-specified propensity score-based matching between groups. Subanalysis during 2 study periods (2013 to 2015 and 2016 to 2017) and among low/intermediate-low and intermediate-high/high volume centers were performed. RESULTS:Among 21,611 patients, 19,995 (92.5%) underwent femoral TAVR and 1,616 (7.5%) underwent n-FP TAVR (transcarotid, n = 914 or trans-subclavian, n = 702). Patients in the n-FP access group had more severe disease (mean logistic EuroSCORE 19.95 vs. 16.95; p < 0.001), with a higher rate of peripheral vascular disease, known coronary artery disease, chronic pulmonary disease, and renal failure. After matching, there was no difference in the rate of post-procedural death and complications according to access site, except for a 2-fold lower rate of major vascular complications (odds ratio: 0.45; 95% confidence interval: 0.21 to 0.93; p = 0.032) and unplanned vascular repairs (odds ratio: 0.41; 95% confidence interval: 0.29 to 0.59; p < 0.001) in those who underwent n-FP access. The comparison of outcomes provided similar results during the second study period and in intermediate-high/high volume centers.CONCLUSIONS:n-FP TAVR is associated with similar outcomes compared with femoral peripheral TAVR, except for a 2-fold lower rate of major vascular complications and unplanned vascular repairs. n-FP TAVR may be favored over surgery in patients who are deemed ineligible for femoral TAVR and may be a safe alternative when femoral access risk is considered too high.

International audience; Background: Robotic assistance is increasingly being used for treatment of early stage of non-small cell lung cancer. Our objectives were to compare the morphine consumption during the postoperative 48 hours after robotic-assisted thoracic surgery and that after video-assisted thoracic surgery as well as compare the patient's haemodynamic and respiratory function during the procedures. Methods: This observational, prospective study was conducted in a single referral centre for thoracic surgery from January 2016 to March 2017. Patients who were scheduled to undergo surgical lung resection were included. A propensity score based on age, sex, American society of Anesthesiology score was used between groups. Linear regression analyses were used to determine the mean difference in the postoperative morphine consumption. We also compared the haemodynamic and respiratory function during the two procedures. Results: Among the 194 patients included, 105 (54%) and 89 (46%) underwent video and robotic surgery, respectively. Total 75 of each group were matched using the propensity score. The consumption of morphine was 23.0 (16.5-39.0) mg and 33.0 (19.3-46.5) mg (P=0.05) in the video and robotic groups, respectively. Linear regression revealed an average difference (95% Cl) of 6.76 mg (0.32-13.26) (P=0.04) in the morphine consumption after adjusting for the body mass index and local anaesthetic use. Robotic surgery was associated with worse haemodynamic and respiratory function than video surgery. Conclusions: As compared with video, robotic surgery was associated with increased use of morphine and greater alteration in the haemmlynarnic and respiratory functions.

International audience; We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc). Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography. Pulmonary function tests, main manifestations and severity of the lung disease (Medsger's severity scale) were collected. KL-6 serum concentrations were significantly higher in SSc-ILD patients than in those without ILD (p < 10(-4)) and were inversely correlated with forced vital capacity, total lung capacity and diffuse lung capacity of carbon monoxide. Serum KL-6 level superior to 872 U/ml appeared as the optimal cut-off value associated with ILD. Patients with a restrictive pulmonary syndrome and dyspnoea had significant higher KL-6 serum concentrations. SSc patients with anti-topoisomerase 1 antibodies had higher KL-6 serum levels than patients with anti-centromere antibodies (p < 10(- 4)). ILD and anti-topoisomerase 1 antibodies were independent factors associated with KL-6 in multivariate analysis. Interestingly, KL-6 serum concentrations positively increased with the patient lung severity. Our study confirms that KL-6 is an accurate biomarker for the diagnosis of SSc-ILD in a French cohort of patients. High KL-6 levels should prompt physicians to assess ILD with pulmonary imaging and pulmonary functions tests. Prospective clinical studies are still required to determine whether levels of KL-6 might predict progression of ILD as well as its usefulness in the timing of therapeutic intervention.

International audience

BackgroundPD1/L1 Immune Checkpoint Inhibitors (ICI) have significantly improved long-term outcome in about 20% of advanced Non Small Cells Lung Cancer (NSCLC) patients (pts), but 80% present primary or secondary resistance. The PIONeeR project (NCT03493581) aims to predict the response/resistance to PD1/L1 ICIs in advanced NSCLC pts through a comprehensive agnostic multiparametric and longitudinal biomarkers assessment. Data presented here are a focus on the quantification of tumor infiltration by lymphocytes, their activation as potential markers of the resistance to treatment by ICI.MethodsAdvanced NSCLC pts with available archived tumor tissue at screening visit (VS), treated with standard PD1/L1 ICIs (nivolumab, pembrolizumab or atezolizumab), alone (2nd line or more) or combined with chemotherapy (1st line), were re-biopsied at 6 weeks (V2) of treatment. PD1/L1 ICIs overall response rate (ORR) was assessed by RECIST 1.1 every 6 weeks. The multiplex IHC test ”Immunoscore® CR T Cells Exhaustion” (IS TCE) quantifies cytotoxic lymphocytes expressing three checkpoints: PD1, LAG3, TIM3, extrapolating their exhaustion status, both in the stroma and parenchyma. The unsupervised neural-network-based machine learning algorithm SOM (Self-Organizing Maps) was used to classify samples based on the 27 IS TCE variables. Statistical significance of survival differences between groups was evaluated using the log-rank test.ResultsAmong the first 100 pts, (male (64%), smokers (91,8%), ConclusionsIS TCE test may help stratifying and predicting responders to anti PD1/L1 therapy through checkpoint expressing lymphocytes quantification and spatial distribution. Additional tests performed on the PIONeeR cohort to explore other aspects of the immune response to cancer should complete these results.AcknowledgementsThis work is supported by French National Research Agency (ANR-17-RHUS-0007), a partnership of AMU, APHM, AstraZeneca, Centre Léon Bérard, CNRS, HalioDx, ImCheck Therapeutics, Innate Pharma, Inserm, Institut Paoli Calmettes and sponsored by AP HM. Drug supply is funded by AstraZeneca. Special thanks to patients and families.Trial RegistrationNCT03493581Ethics ApprovalThe study is conducted in accordance with Good Clinical Practice and the French applicable regulatory requirements (Public Health Code, article L.1121-1/La loi n° 2012–300 du 5 mars 2012 relative aux recherches impliquant la personne humaine (dite loi Jardé), the applicable subject privacy requirements, and the ethical principles that are outlined in the Declaration of Helsinski. The study was approved by the French Ethic Committee, CPP Ouest II - Angers, ref. CPP: 2028/08, Ref ANSM (French competent authority) 2018020500208, 2018072600120, 2019083000148. Freely given written informed consent was signed and obtained from each individual participating in the study, before any study specific procedure was undertaken and after the provision of information about the study by the investigator during a physician-patient consultation and sufficient time for reflection.

Aims Reimplantation of cardiac implantable electronic devices (CIEDs) after extraction due to device infection is a major issue in pacemaker-dependent patients. We compared in-hospital and long-term outcomes with two techniques: epicardial reimplantation (EPI) before CIED extraction and temporary pacing (TP) with a view to delayed endocardial reimplantation. Methods and results Two cohorts of consecutive pacemaker-dependent patients who underwent transvenous lead extraction at our tertiary centre were included in this retrospective cohort study. According to successive policies, either the EPI or the TP approach was used. In-hospital complications occurred at similar rates in the EPI (n = 59) and TP (n = 52) cohorts (37.3% vs. 32.7%, respectively; P = 0.61). Thirteen (25.0%) patients in the TP cohort eventually were reimplanted epicardially, mainly because of infection of the temporary lead. Finally, 65 patients were discharged with an epicardial device and 37 with an endocardial device. Median follow-up was 41.7 (interquartile range 34.1-51.5) months. No difference was observed in long-term mortality according to the reimplantation strategy, but use of TP was associated with a reduced risk of late endocarditis and device reintervention (hazard ratio (HR) 0.25, 95% confidence interval (CI) 0.09-0.069, P = 0.01), whereas epicardial device reimplantation was associated with an increased risk (HR 3.62, 95% CI 1.07-12.21, P = 0.04). Conclusion We observed similar in-hospital outcomes in our EPI and TP cohorts. Twenty-five percent of the patients initially paced by a TP strategy finally needed an epicardial device, mainly because of infection of their TP lead. Use of TP resulted in lower rates of late endocarditis and device reintervention.

Objectif Evaluer la qualite de vie des enfants en âge scolaire nes avant 28 SA et qui n’ont aucune incapacite majeure. Population et methode Etude transversale multicentrique (QPQoL study) incluant des nouveau-nes Resultats Quarante (7,5%) enfants gravement handicapes ont ete exclus. Parmi les 471 enfants eligibles, 169 (36%) etaient perdus de vu lors du suivi et donc 302 (64%) etaient inclus dans l’etude. Le terme moyen de naissance etait de 26.2 SA (± 0.8), le poids moyen de naissance etait de 879 g (± 181) et l’âge moyen de suivi des enfants etait de 8.4 ans (± 0.8). 48% des participants presentaient des deficiences cognitives mineures ou moderees d’apres leur Indice FSIQ. La memoire de travail, l’attention et la flexibilite mentale avaient une moyenne faible par rapport au groupe de reference. Hormis les relations familiales, l’evaluation de la qualite de vie par VSPA et Kidscreen 10 a ete significativement plus faible selon le point de vue des enfants et des parents. Les enfants ont declare une qualite de vie significativement diminuee dans les domaines suivants: les relations amicales, l’estime de soi et les loisirs, tandis que parents avaient indique: le bien-etre psychologique, le travail scolaire et la vitalite. Les enfants ayant un FSIQ ≥ 89, consideres comme normaux, avaient une qualite de vie inferieure. Des deficiences cognitives/comportementales specifiques (retard de langage, dyspraxie visuo-spatiale et troubles dysexecutifs) etaient les determinants significatifs de la qualite de vie dans les domaines des performances scolaires et de l’image corporelle. Conclusion La qualite de vie d’un enfant ne tres grand premature en âge scolaire sans deficience grave etait inferieure a celle d’une population de reference d’enfants nes a terme, tant du point de vue des parents que de celui de l’enfant. Cette evaluation devrait permettre de mieux comprendre le devenir a long terme et d’offrir un soutien adapte a l’enfant et a sa famille. Ethique This study was approved by the CPP (Committee for the Protection of Persons) (18/12/2012 ref 12.018) and is registered on ClinicalTrials.gov, number NCT01675726 .

Objectives Non-conventional aPL have been described in patients presenting clinical manifestations of antiphospholipid syndrome but negative for conventional markers. Among them, detection of autoantibodies against prothrombin has been proposed to improve diagnosis and management of these patients. However autoantibodies against prothrombin are heterogeneous and their use in clinical practice still remains unclear. The aim of this study was to evaluate the interest of IgG and IgM autoantibodies directed against the prothrombin only (aPT). Methods We retrospectively studied IgM and IgG aPT results, conventional antiphospholipid syndrome markers and clinical data of a large cohort of 441 patients referred for antiphospholipid syndrome exploration with aPT detection over a period of 5 years. Results We observed a total prevalence of 17% of aPT-positive patients (75/441). A significant association was found between aPT and thrombosis (P = 0.035), with 70% of patients having unexplained thrombosis, aPT representing the sole aPL detected. aPT positivity was significantly more frequent in venous thrombosis than in arterial thrombosis (P = 0.004). Interestingly, we demonstrated for the first time that aPT IgG levels were higher in recurrent thrombosis than in isolated thrombosis (P = 0.013), leading us to propose a predictive level of recurrence for thrombosis. Conclusion Our results show that aPT are associated with thrombosis and demonstrate the interest of assessing both IgG and IgM aPT, in particular in venous thrombosis when conventional markers are negative. Quantification of aPT could predict recurrence of thrombosis and influence subsequent treatment strategy. Prospective clinical studies are now required to confirm these results.