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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.

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

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: 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.

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.

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.

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.

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; 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.

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.

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.

This case study reports the training of an elite 25-km open-water swimmer and the daily heart rate variability (HRV) changes during the 19-week period leading to his world champion title. Training load was collected every day and resting HRV was recorded every morning. The swimmer’s characteristics were V̇O2max: 58.5 ml·min−1·kg−1, maximal heart rate: 178 beats per minute, and maximal ventilation: 170 L·min−1. Weekly training volume was 85±21 km, 39±8% was at [La]b4 mmol·L−1 (Z3). In the supine position, the increase in training volume and Z2 training were related to increases in rMSSD and HF. In the standing position, an increase in parasympathetic activity and decrease in sympathetic activity were observed when Z1 training increased. Seasonal changes indicated higher values in the LF/HF ratio during taper, whereas higher values in parasympathetic indices were observed in heavy workload periods. This study reports extreme load of an elite ultra-endurance swimmer. Improvements in parasympathetic indices with increasing Z2 volume indicate that this training zone was useful to improve cardiac autonomic activity, whereas Z1 training reduced sympathetic activity.

Cesarean delivery rates at extreme prematurity have regularly increased over the past years, and few previous studies have investigated severe maternal morbidity associated with extreme preterm cesarean delivery.The aim of this study was to evaluate whether gestational age26 weeks of gestation (weeks) was associated with severe maternal morbidity and mortality (SMMM) of preterm cesarean deliveries in comparison with cesarean deliveries between 26 and 34 weeks.The Etude Epidémiologique sur les petits âges gestationnels (EPIPAGE) 2 is a national prospective population-based cohort study of preterm births in 2011. We included mothers with cesarean deliveries between 22 and 34 weeks, excluding those who had a cesarean delivery for the second twin only and those with pregnancy terminations. SMMM was analyzed as a composite endpoint defined as the occurrence of at least 1 of the following complications: severe postpartum hemorrhage defined by the use of a blood transfusion, intensive care unit admission, or death. To assess the association of gestational age26 weeks and SMMM, we used multivariate logistic regression and a propensity score-matching approach.Among 2525 women having preterm cesarean deliveries, 116 before 26 weeks and 2409 between 26 and 34 weeks, 407 (14.4%) presented with SMMM. The SMMM occurred in 31 mothers (26.7%) who were at gestational age26 weeks vs 376 (14.2%) between 26 and 34 weeks (P .001). Cluster multivariate logistic regression showed significant association of gestational age26 weeks and SMMM (adjusted odds ratio [aOR], 2.50; 95% confidence interval [CI], 1.42-4.40) and propensity score-matching analysis was consistent with these results (aOR, 2.27; 95% CI, 1.31-3.93).Obstetricians should know about the higher SMMM associated with cesarean deliveries before 26 weeks, integrate this knowledge into decisions regarding cesarean delivery, and be prepared to manage the associated complications.

ObjectiveAtrial fibrillation (AF) is one of the most common side effects of ibrutinib, a drug that has dramatically improved the prognosis of chronic B-cell malignancies such as chronic lymphocytic leukaemia (CLL). The true incidence of ibrutinib-related AF (IRAF) is not well known and its therapeutic management poses unique challenges especially due to the inherent risk of bleeding. We aimed to determine the incidence and predictors of IRAF, and to analyse its management and outcome.MethodsA standardised monitoring was applied at two cardio-oncology clinics in consecutive patients referred before and during ibrutinib therapy. The primary endpoint was the incidence of IRAF. The excess of AF incidence with ibrutinib was studied by comparing the incidence of IRAF with the expected incidence of AF in general population and in patients with CLL not exposed to ibrutinib.Results53 patients were included. The incidence of IRAF was 38% at 2 years and the risk was 15-fold higher than the AF risk in both the general population and patients with CLL not exposed to ibrutinib (p2 at treatment initiation identified patients at high risk of developing IRAF. No major bleeding events occurred in patients on ibrutinib, although the majority of patients with IRAF were treated with anticoagulants.ConclusionsThis cardio-oncology study showed that the risk of IRAF was much higher than previously reported. The majority of cases occurred in asymptomatic patients justifying close monitoring.

BACKGROUND Surgical treatment of secondary mitral regurgitation (SMR) is controversial. AIM To analyse outcome after undersizing annuloplasty (UA) and mitral valve replacement (MVR). METHODS Consecutive patients operated on for severe SMR, with left ventricular ejection fraction (LVEF)

International audience; The clinical venous thromboembolism (VTE) pattern often shows wide heterogeneity within relatives of a VTE-affected family, although they carry the same thrombophilia defect. It is then mandatory to develop additional tools for assessing VTE risk in families with thrombophilia. This study aims to assess whether common environmental and genetic risk factors for VTE contribute to explain this heterogeneity. A total of 2,214 relatives from 651 families with known inherited thrombophilia were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2013. A thrombophilia screening was systematically performed in all included relatives. According to the severity of the thrombophilia defect, individuals were split into three groups: no familial defect, mild thrombophilia, and severe thrombophilia. In addition, common genetic factors (ABO blood group and 11 polymorphisms selected on the basis of their association with VTE in the general population) were genotyped. Furthermore, body mass index and smoking were collected. VTE incidence was 1.74, 3.64, and 6.40 per 1,000 person-years in individuals with no familial defect, mild thrombophilia, and severe thrombophilia, respectively. Five common risk factors were associated with VTE in this population: obesity, smoking, ABO blood group, and F11_rs2036914 and FGG_rs2066865 polymorphisms. These common factors were then included into a three-level risk score. The score was highly efficient for assessing VTE risk in mild thrombophilia patients by identifying two groups with different VTE risk; individuals with low score had the same risk as individuals with no familial defect whereas individuals with high score had the same risk as individuals with severe thrombophilia. An overall score including the five items plus the thrombophilia status was built and displayed an area under the receiver operating characteristic curve of 0.702 for discriminating VTE and non-VTE relatives. In conclusion, integrating common environmental and genetic risk factors improved VTE risk assessment in relatives from families with thrombophilia. Ã Equally contributed to the article.

International audience; Background Iron deficiency (ID) is common in heart failure (HF), and is associated with unfavourable clinical outcomes. Although it is recommended to screen for ID in HF, there is no clear consensus on the optimal timing of its assessment. Aim To analyse changes in iron status during a short-term follow-up in patients admitted for acute HF. Methods Iron status (serum ferritin concentration and transferrin saturation) was determined in 110 consecutive patients (median age: 81 years) admitted to a referral centre for acute HF, at three timepoints (admission, discharge and 1 month after discharge). ID was defined according to the guidelines. Results The prevalence rates of ID at admission, discharge and 1 month were, respectively, 75% (95% confidence interval [CI] 67–83%), 61% (95% CI: 52–70%), and 70% (95% CI: 61–79%) (P = 0.008). Changes in prevalence were significant between admission and discharge (P = 0.0018). Despite a similar ID prevalence at admission and 1 month (P = 0.34), iron status changed in 25% of patients. Between admission and discharge, variation in C-reactive protein correlated significantly with that of ferritin (ρ = 0.30; P = 0.001). Advanced age, anaemia, low ferritin concentration and low creatinine clearance were associated with the persistence of ID from admission to 1 month. Conclusions Iron status is dynamic in patients admitted for acute HF. Although ID was as frequent at admission as at 1 month after discharge, iron status varied in 25% of patients.; Contexte La carence martiale (CM) est fréquente dans l’insuffisance cardiaque (IC) et associée à un pronostic défavorable. Bien qu’il soit recommandé de la dépister au cours de l’IC, il n’existe pas de consensus quant au moment optimal de réalisation du bilan martial. Nous avons analysé l’évolution du bilan martial au cours du suivi à court terme de patients hospitalisés pour IC aiguë. Méthodes Un bilan martial (taux sérique de ferritine et coefficient de saturation de la transferrine) a été effectué chez 110 patients consécutifs (âge médian : 81 ans) admis pour IC aiguë dans un centre de référence à trois moments différents (admission, sortie et 1 mois après la sortie). La carence martiale était définie conformément aux guidelines. Résultats Les taux de prévalence de la CM à l’admission, à la sortie et à 1 mois étaient respectivement de 75 % (intervalle de confiance [IC] 95 %, 67 % 83 %), 61 % (IC : 95 %, 52 % 70 %) et 70 % (IC : 95 %, 61 % 79 %) (p = 0,008). Ces changements de prévalence étaient significatifs entre l’admission et la sortie (p = 0,0018). Malgré une prévalence de la CM similaire entre l’admission et 1 mois (p = 0,34), le bilan martial avait changé chez 25 % des patients. Entre l’admission et la sortie, la variation de la protéine C-réactive était significativement corrélée à celle de la ferritine (ρ = 0,30; p = 0,001). L’âge avancé, l’anémie, un faible taux de ferritine et la faible clairance de la créatinine étaient associés à la persistance de la CM entre l’admission et 1 mois. Conclusions Le bilan martial est dynamique chez les patients admis pour une IC aiguë. Bien que la CM soit aussi fréquente à l’admission qu’à 1 mois après la sortie, le bilan martial varie chez 25 % des patients.

International audience; Bivalirudin is associated with an increased risk of acute stent thrombosis (AST) compared to unfractionated heparin (UFH) in acute coronary syndrome patients (ACS) during short-duration percutaneous coronary intervention (PCI). The mechanisms involved are unknown. We aimed to investigate the antithrombotic efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we prospectively enrolled 30 patients undergoing PCI for a non– ST elevation ACS. They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg) or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at the time of PCI. The VASP index and activated partial thromboplastin time (aPTT) were used to assess the course of platelet reactivity (PR) and antithrombotic activity. The two groups were similar regarding baseline, angiographic, and interventional characteristics. There was no difference between the two groups in the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4 h after the LD of ticagrelor. The level of antithrombotic activity was significantly lower in the bivalirudin group compared to the UFH group (p < 0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to the excess in thrombotic acute events observed during short-duration PCI.

Objective To evaluate whether gestational age was associated with the severe maternal morbidity (SMM) of preterm cesarean delivery between 22 and 34 weeks of gestation (weeks). Material and methods We performed an observational retrospective cohort study in two tertiary university hospitals in 2018. We included all mothers of preterm infants born by caesarean delivery between 22 and 34 weeks, excluding mothers with multiple births greater than two, with pregnancy terminations or stillbirths, and who died unrelated to obstetrical causes. The principal endpoint, SMM, was a composite outcome (classical uterine incision, postpartum hemorrhage defined by blood loss ≥ 500 mL, blood transfusion, any injury to adjacent organs, unplanned procedure/need for reintervention, Intensive Care Unit (ICU) stay longer than 24 h, postpartum fever, and/or death). Results Among the 252 women, SMM occurred in 89 (35.3 %) cases. After multivariate analysis, gestational age was independently associated with SMM (adjusted Odds Ratio [aOR] 0.87; 95 % Confidence Interval [CI] 0.78−0.97). The other variables statistically associated with SMM were type of pregnancy with a negative association with twin pregnancy (aOR, 0.44; 95 % CI, 0.20−0.93) and a positive association with general anesthesia (aOR, 2.52; 95 % CI, 1.25−5.13). A sensitivity analysis was performed and found an association, at the limit of significance, between gestational age Conclusion Lower gestational age was associated with the risk of SMM for preterm caesarean delivery between 22 and 34 weeks. Obstetricians should integrate this knowledge into their shared decision-making processes with parents.

International audience; Objectives:To investigate whether adenosine A2A receptors lead to vasodilation and positive inotropic function under stimulation and whether they play a role in the control of blood pressure in patients with cardiogenic shock.Design:Prospective observational study.Setting:Monocentric, Hopital Nord, Marseille, France.Subjects:Patients with cardiogenic shock (n = 16), acute heart failure (n = 16), and acute myocardial infarction (n = 16).Interventions:None.Measurements and Main Results:Arterial adenosine plasma level and A2A receptor expression on peripheral blood mononuclear cells were evaluated by mass spectrometry and Western blot, respectively, at admission and after 24 hours. Hemodynamic parameters, including systemic vascular resistance, were also assessed. Mean adenosine plasma level at admission was significantly higher in patients with cardiogenic shock (2.74 ± 1.03 µM) versus acute heart failure (1.33 ± 0.27) or acute myocardial infarction (1.19 ± 0.27) (normal range, 0.4–0.8 µM) (p < 0.0001). No significant correlation was found between adenosine plasma level and systemic vascular resistance. Mean adenosine plasma level decreased significantly by 24 hours after admission in patients with cardiogenic shock (2.74 ± 1.03 to 1.53 ± 0.68; p < 0.001). Mean A2A receptor expression was significantly lower in patients with cardiogenic shock (1.18 ± 0.11) versus acute heart failure (1.18 ± 0.11 vs 1.39 ± 0.08) (p = 0.005).Conclusions:We observed high adenosine plasma level and low A2A receptor expression at admission in patients with cardiogenic shock versus acute heart failure or acute myocardial infarction. This may contribute to the physiopathology of cardiogenic shock.

IntroductionSevere haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life.Methods and analysisWe present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14–17 years) with those from a group of young adults (aged 20–29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants’ views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag.Ethics and disseminationThe study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public.Trial registration numberNCT02866526; Pre-results.

Infections of cardiac implantable electronic devices (CIEDs) have increased over the past decade. However, the impact of the climate on CIED infections is unknown. To determine whether there is a seasonal variation in CIED infections. In this single-center observational study, retrospective analysis of prospectively collected data was performed. Timone Hospital in Marseille (south-east France) is a tertiary care institution and the regional reference center for management of CIED infections. All consecutive patients with CIED extractions for infectious reasons were included over a 12-year period. We noted the mean temperature (°C), precipitation (mm) and the incidence of CIED infections over this period. Among 612 patients [mean (standard deviation) age, 72.4 (13.0) years; 74.0% male], 238 had endocarditis alone (38.9%), 249 had pocket infection alone (40.7%), and 125 had both (20.4%). We found bacterial documentation in 428 patients (70.0%), commensal in 245 (40.0%). The incidence of CIED infections was positively associated with high temperature (regression coefficient = 0.075; P = 0.01) and precipitation (regression coefficient = 0.022; P 0.01). Seasonal variation was specific of pocket infections, whether they were associated with endocarditis or not. Subgroups with infection seasonality were: women, elderly people ( 75 years), late CIED infection and skin commensal bacterial infections. We found a seasonal variation in pocket infections, whether associated with endocarditis or not. Infections were associated with elevated temperatures and precipitation. Therefore, specific prevention strategy should be discussed in high-risk patients.

Objective To investigate the headache characteristics and clinical features of elderly migraine patients at a tertiary headache center. Methods We retrospectively reviewed 239 records of migraine patients, over the age of 64 at the first visit, who had migraine as defined by the International Classification of Headache Disorders 3rd edition (beta version) from 2006 to 2015 based on the Marseille registry at Timone Hospital. Results 13.8% (33/239) patients had migraine with aura only, 13.0% (31/239) had both diagnoses. Of the patients who presented with migraine with aura, 13.4% (32/239) presented with aura without headache. Unilateral pain location was reported by 58.6% (140/239) of patients and the throbbing type of pain was present in 50.2% (120/239) of our study group. Photo- and phonophobia were observed in 77.4% (185/239) and 79.5% (190/239) of patients. Seventy-nine out of 239 (30.1%) patients were found to have probable medication overuse. Within this group, 31.65% (25/79) overused triptan and 70.9% (56/79) overused combination analgesics. We found higher frequencies of migraine for patients whose age at onset of migraine was younger than 18 years, and low frequency migraine was reported more frequently in the later onset group (P = .0357). Discussion We assess the headache characteristics of elderly migraine patients who were seen at our tertiary headache center and report the high frequency of probable medication overuse headache in this study group. Finally, we suggest that age of onset is an important factor in the clinical profile of these patients.

Essentials Acute coronary syndrome (ACS) with atrial fibrillation (AF) is a therapeutic challenge. Dual and triple antithrombotic therapy showed a similar thrombotic risk in ACS patients with AF. The omission of aspirin during the first month did not increase the rate of ischemic events. Replacement of vitamin K antagonist by dabigatran leads to an increased thrombotic risk. SUMMARY Background Dual antithrombotic therapy comprising a vitamin K antagonist (VKA) plus clopidogrel reduces the incidence of major bleeding compared with triple therapy (VKA + clopidogrel + aspirin) in acute coronary syndrome (ACS) patients with atrial fibrillation (AF), with a similar thrombotic risk. The oral thrombin inhibitor dabigatran (150 mg twice a day) showed superiority over VKA in non-valvular AF, but data supporting its use in AF patients presenting with ACS are limited. Objective We sought to evaluate the efficacy of dabigatran vs. VKA in the management of AF patients undergoing percutaneous coronary intervention for an ACS. Methods In this open-label study, 133 consecutive patients received dabigatran plus clopidogrel. Another cohort of 133 patients treated with VKA plus clopidogrel was used as the control group. Results After propensity score adjustment, the cumulative incidence of major adverse cardiovascular events over 24 months was higher with dabigatran vs. VKA (adjusted hazard ratio, 2.28; 95% confidence interval, 1.46-3.56). Similar rates of major bleeding were found (adjusted hazard ratio, 1.17; 95% confidence interval, 0.46-2.96). Conclusions In AF patients presenting with ACS, replacement of VKA by dabigatran concurrently with clopidogrel is associated with an increased thrombotic risk, without a reduction in major bleeding.

Summary Background Guidelines recommend careful screening and treatment of coronary artery disease (CAD) in heart failure with preserved or mid-range ejection fraction (HFpEF/HFmEF). Aim We aimed to determine the prevalence and characteristics of CAD using a prospective systematic coronary angiography approach. Methods A systematic coronary angiography protocol was applied in consecutive patients admitted for HFpEF/HFmEF during a 6-month period in a single centre. History of CAD and results of angiography, including revascularization, were reported. Results Of the 164 patients with HFpEF/HFmEF who were included, an angiography assessment was applied in 108 (66%) (median age: 79 years [interquartile range: 70–85 years]; 54% were women). In our analysis, 64% (95% confidence interval [CI] 55–73%) of patients had a significant coronary stenosis corresponding to a global CAD prevalence of 80% (95% CI 73–88%). The prevalence of CAD was similar for HFpEF and HFmEF. The left main coronary artery presented a significant stenosis in 6.5% of cases and 39% of patients had a two- or three-vessel disease. The rate of significant coronary stenosis was non-significantly higher in patients with a history of CAD. Patients with HFpEF/HFmEF with and without CAD did not differ in clinically meaningful ways, in terms of symptoms or laboratory and echocardiography results. This strategy led to complete revascularization in 36% of patients with significant stenosis and in 23% of all patients with HFpEF/HFmEF. Conclusions Our study differs from others in that we used a systematic angiography approach. The results suggest a much higher prevalence of CAD in HFpEF/HFmEF than previously reported and should encourage clinicians to aggressively identify this co-morbidity.

Background. - An optimal maximum time of 60 minutes has been recommended in recent guide lines for the first evaluation and treatment of patients with acute heart failure (AHF); however, this has not been tested prospectively. Aim. - To analyze the impact of a time-to-treatment (TTT) strategy of < 60 minutes on the in-hospital outcome of patients with AHF. Methods. - During a single 1-month period, we consecutively enrolled all patients hospitalized with AHF in a prospective cohort. In this pilot study, TTT was defined as the time between the first medical contact to the onset of the first medical intervention. The primary outcome was a composite including in-hospital death or worsening AHF. Results. - Of the 74 patients included, 23 (31%) had a TTT of < 60 minutes. Although these patients were more likely to have a more severe episode of AHF, the primary outcome occurred only in patients with a TTT of >= 60 minutes. The primary outcome was significantly associated with a TTT of >= 60 minutes (P=0.036), low systolic blood pressure (P

Background The rapid and reliable exclusion of myocardial revascularization is a major unmet clinical need in patients with suspected coronary artery disease ( CAD ) and non‐contributive electrocardiography and troponin. Non‐invasive tests have high rates of false positives and negatives, and there is no biomarker to assess myocardial ischemia. The presence of spare adenosine A 2A receptors (A 2 A R )—characterized by a high dissociation constant/half maximal effective concentration ( K D / EC 50 ) ratio—expressed on peripheral blood mononuclear cells ( PBMC ) has been associated with ischemia during exercise stress testing in patients with CAD . In this work, we investigated the diagnostic accuracy of spare A 2 A R versus fractional flow reserve ( FFR ) in patients with suspected CAD . Methods and Results Sixty patients with suspected CAD , but non‐contributive electrocardiography and troponin, were consecutively enrolled in this prospective study. The binding ( K D ), functional response (cyclic adenosine monophosphate [ cAMP ] production; EC 50 ) on PBMC A 2 A R were compared with FFR results. Patients were divided into 3 groups: 17 (group 1) with normal coronary angiography (n=13) or stenosis CAD and non‐significant FFR (group 2); and 22 with CAD and significant FFR (group 3). Median K D / EC 50 was 6‐fold higher in group 3 (4.20; interquartile range: 2.81–5.00) than group 2 (0.66; interquartile range: 0.47–1.25) and 7‐fold higher than group 1 (0.60; interquartile range: 0.30–0.66). Conclusions In patients with suspected CAD and non‐contributive electrocardiography and troponin, the absence of spare A 2 A R on PBMC may help to rule out myocardial ischemia. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 03218007.

We would like to thank Dr. Bayman and Dr. Brennan for their interesting comments about our study.