Publications by authors named "Noémie Resseguier"

68 Publications

Severe maternal morbidity in preterm cesarean delivery: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2021 Apr 21;261:116-123. Epub 2021 Apr 21.

Department of Obstetrics and Gynecology, Nord Hospital, APHM, Chemin des Bourrely, 13015, Marseille, France; EA3279, CEReSS, Health Service Research and Quality of Life Center, Aix-Marseille University, 13284, Marseille, France.

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 < 26 weeks; 42,132 delivering between 26 and 34 weeks) were included. SMM occurred in 607 women (17.6 %) < 26 weeks and 4,483 women (10.6 %) between 26 and 34 weeks. Gestational age < 26 weeks was associated with an increased risk of SMM (RR, 1.65; 95 % CI [Confidence Interval], 1.52-1.78; I = 40 %). Gestational age < 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 < 25 weeks was also associated with SMM in preterm cesarean delivery (RR, 1.66; 95 % CI, 1.50-1.83; I = 3%).

Conclusions: Gestational age < 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.
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http://dx.doi.org/10.1016/j.ejogrb.2021.04.022DOI Listing
April 2021

Impact of Platelet Reactivity in ACS Patients on Clinical Outcomes with Triple Antithrombotic Therapy.

J Clin Med 2021 Apr 8;10(8). Epub 2021 Apr 8.

Department of Cardiology, ARCHANTEC, School of Medicine, Aix Marseille University, 13007 Marseille, France.

Optimal antithrombotic therapy after percutaneous coronary intervention (PCI) in patients on oral anticoagulants (OAC) remains a clinical conundrum. In fact, combining an OAC with dual antiplatelet therapy (triple antithrombotic therapy, TAT) increases the risk of bleeding. Clopidogrel is the only thienopyridine recommended in TAT patients. Whether its response plays a relevant role in this setting remains uncertain. We aimed to evaluate the level of platelet reactivity inhibition (PRI) achieved by oral TAT in Acute Coronary Syndrome (ACS) patients undergoing PCI and its relationship with outcomes. We performed a multicenter prospective observational study and assessed PRI by vasodilator-stimulated phosphoprotein (VASP) index following a loading dose of clopidogrel. The primary endpoint was the incidence of major adverse cerebral or cardiovascular events (MACCE) at six months based on High on Treatment Platelet Reactivity (HTPR, VASP > 50%). The secondary endpoint was the incidence of bleeding at six months based on Low on Treatment Platelet Reactivity (LTPR, VASP < 16%). 491 patients were followed up for six months: 7.7% experienced MACCE and 17.3% experienced bleeding. There was no significant relationship between HTPR and MACCE, neither between LTPR and bleeding. Vitamin-K antagonist (VKA) treatment was associated with more MACCE and bleeding events, and the majority of events occurred within the first months. VASP index failed to predict outcomes in post-ACS patients with TAT. We confirm that direct acting OAC should be prioritized over VKA in TAT regimen.
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http://dx.doi.org/10.3390/jcm10081565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068113PMC
April 2021

Rapid deployment versus trans-catheter aortic valve replacement in intermediate-risk patients: A propensity score analysis.

J Card Surg 2021 Jun 9;36(6):2004-2012. Epub 2021 Mar 9.

Department of Cardiac Surgery, La Timone Hospital, Marseille, France.

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/m , 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.
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http://dx.doi.org/10.1111/jocs.15483DOI Listing
June 2021

In Vitro Co-Exposure to CeO Nanomaterials from Diesel Engine Exhaust and Benzo()Pyrene Induces Additive DNA Damage in Sperm and Cumulus Cells but Not in Oocytes.

Nanomaterials (Basel) 2021 Feb 13;11(2). Epub 2021 Feb 13.

IMBE, CNRS, IRD, Avignon Université, Aix Marseille Univ., 13005 Marseille, France.

Benzo(a)pyrene (BP) 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 (CeO NMs), which are used in nano-based diesel additives to decrease the emission of toxic compounds and to increase fuel economy. The toxicity of CeO NMs on reproductive organs and cells has also been shown. However, the effect of the combined interactions of BP and CeO NMs on reproduction has not been investigated. Herein, human and rat gametes were exposed in vitro to combusted CeO NMs or BP or CeO NMs and BP in combination. CeO 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 CeO NMs (1 µg·L) or BP (1.13 µmol·L) in all cell types considered compared to unexposed cells. Co-exposure to the CeO NMs-BP 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.
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http://dx.doi.org/10.3390/nano11020478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918929PMC
February 2021

Smartwatch Electrocardiogram and Artificial Intelligence for Assessing Cardiac-Rhythm Safety of Drug Therapy in the COVID-19 Pandemic. The QT-logs study.

Int J Cardiol 2021 05 29;331:333-339. Epub 2021 Jan 29.

Institut Cardiovasculaire Paris-Sud, Hôpital Privé Jacques Cartier, Ramsay, Massy, France.

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 <50 ms in 98.2% of patients.

Conclusion: In real-world epidemic conditions, AI-QTc duration measured by SW-ECG is in fair agreement with manual measurements on 12‑lead ECGs. Following further validation, AI-assisted SW-ECGs may be suitable for QTc interval monitoring.

Registration: ClinicalTrial.govNCT04371744.
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http://dx.doi.org/10.1016/j.ijcard.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845555PMC
May 2021

Prosthesis-patient mismatch is an independent predictor of congestive heart failure after transcatheter aortic valve replacement.

Arch Cardiovasc Dis 2021 Jan 25. Epub 2021 Jan 25.

Department of Cardiac Surgery, La Timone Hospital, 264, rue Saint-Pierre, 13005 Marseille, France.

Background: Little is known about the effect of prosthesis-patient mismatch (PPM) on outcomes 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)≤0.85cm/m, and severe PPM by an iEOA<0.65cm/m. 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; P=0.01), a lower iEOA (0.73±0.08 vs 1.11±0.22 cm/m; P<0.001) and a higher mean gradient (14±4.6 vs 11.9±3.9mmHg; P<0.001). CHF occurred in 16.5% vs 7% (P=0.03). By multivariable analysis, PPM was independently associated with CHF (hazard ratio [HR] 3.17, 95% confidence interval [CI] 1.17 to 8.55; P=0.032), especially in patients with mitral regurgitation≥2/4 (HR>100, 95%CI>100 to>1000; P<0.01). PPM did not correlate with all-cause mortality (HR 0.90, 95%CI 0.22 to 3.03; P=0.86).

Conclusions: PPM after S3-THV implantation is strongly associated with CHF at 1 year, but is not correlated with overall mortality.
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http://dx.doi.org/10.1016/j.acvd.2020.11.005DOI Listing
January 2021

CeO Nanomaterials from Diesel Engine Exhaust Induce DNA Damage and Oxidative Stress in Human and Rat Sperm In Vitro.

Nanomaterials (Basel) 2020 Nov 24;10(12). Epub 2020 Nov 24.

IMBE, CNRS, IRD, Avignon Université, Aix Marseille University, 13005 Marseille, France.

Cerium dioxide nanomaterials (CeO 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 CeO NMs in the priority list of nanomaterials that require urgent evaluation, and the potential hazard of aged CeO NM exposure remains unexplored. Herein, human and rat sperm cells were exposed in vitro to a CeO NM-based diesel additive (called Envirox), burned at 850 °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 µg·L) using the alkaline comet assay (ACA). We also showed a significant increase in oxidative stress in human sperm after in vitro exposure to 1 µg·L aged CeO NMs evaluated by the HDCF-DA probe. Electron microscopy showed no internalization of aged CeO 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 CeO NMs could exert in vitro biological effects on human spermatozoa and generate ROS.
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http://dx.doi.org/10.3390/nano10122327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760532PMC
November 2020

Phenotypic Characteristics and Development of a Hospitalization Prediction Risk Score for Outpatients with Diabetes and COVID-19: The DIABCOVID Study.

J Clin Med 2020 Nov 20;9(11). Epub 2020 Nov 20.

Department of Endocrinology, Metabolic Diseases and Nutrition, Pôle ENDO, APHM, 13005 Marseille, France.

Diabetes mellitus (DM) has been identified as a risk factor for severe COVID-19. DM is highly prevalent in the general population. Defining strategies to reduce the health care system burden and the late arrival of some patients thus seems crucial. The study aim was to compare phenotypic characteristics between in and outpatients with diabetes and infected by COVID-19, and to build an easy-to-use hospitalization prediction risk score. This was a retrospective observational study. Patients with DM and laboratory- or CT-confirmed COVID-19, who did ( = 185) and did not ( = 159) require hospitalization between 10 March and 10 April 2020, were compared. Data on diabetes duration, treatments, glycemic control, complications, anthropometrics and peripheral oxygen saturation (SpO) were collected from medical records. Stepwise multivariate logistic regressions and ROC analyses were performed to build the DIAB score, a score using no more than five easy-to-collect clinical parameters predicting the risk of hospitalization. The DIAB score was then validated in two external cohorts ( = 132 and = 2036). Hospitalized patients were older (68.0 ± 12.6 vs. 55.2 ± 12.6 years, < 0.001), with more class III obesity (BMI ≥ 40 kg/m, 9.7 vs. 3.5%, = 0.03), hypertension (81.6 vs. 44.3%, < 0.0001), insulin therapy (37% vs. 23.7%, = 0.009), and lower SpO (91.6 vs. 97.3%, < 0.0001) than outpatients. Type 2 DM (T2D) was found in 94% of all patients, with 10 times more type 1 DM in the outpatient group (11.3 vs. 1.1%, < 0.0001). A DIAB score > 27 points predicted hospitalization (sensitivity 77.7%, specificity 89.2%, AUC = 0.895), and death within 28 days. Its performance was validated in the two external cohorts. Outpatients with diabetes were found to be younger, with fewer diabetic complications and less severe obesity than inpatients. DIAB score is an easy-to-use score integrating five variables to help clinicians better manage patients with DM and avert the saturation of emergency care units.
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http://dx.doi.org/10.3390/jcm9113726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699790PMC
November 2020

Hemodynamic Profiles of Cardiogenic Shock Depending on Their Etiology.

J Clin Med 2020 Oct 22;9(11). Epub 2020 Oct 22.

Cardiology Department, APHM, Mediterranean Association for Research and Studies in Cardiology (MARS Cardio), Centre for CardioVascular and Nutrition Research (C2VN), Aix-Marseille Univ, INSERM 1263, INRA 1260, Hopital Nord, 13015 Marseille, France.

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): 1895-2277) vs. 2622 (2264-2993) dynes-s·cm·m ( = 0.002). A trend toward a higher CI was observed: respectively 2.13 (1.88-2.18) vs. 1.78 (1.65-1.96) L·min·m ( = 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.
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http://dx.doi.org/10.3390/jcm9113384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690259PMC
October 2020

Left atrial dysfunction as marker of poor outcome in patients with hypertrophic cardiomyopathy.

Arch Cardiovasc Dis 2021 Feb 7;114(2):96-104. Epub 2020 Oct 7.

Cardiology Department, La Timone Hospital, AP-HM, 13005 Marseille, France; IHU-Méditerranée Infection, Aix-Marseille University, IRD, AP-HM, MEPHI, 13005 Marseille, France. Electronic address:

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±278pg/mL. By echocardiography, left ventricular (LV) ejection fraction (EF) was 67±10%, LV thickness 21±5mm and European Society of Cardiology HCM risk score 3±3%, with 109 patients (36%) presenting obstructive HCM (LV outflow gradient 21±32mmHg). LA diameter was 41±8mm [with 109 (36%) presenting LA diameter ≥40mm], LA volume index 50±26mL/m, PALS 24±13%, PACS 11±7% and LA peak systolic strain rate (LASRs) 1.7±0.6 s. 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<0.0001]. After comprehensive adjustment, PALS remained strongly associated with worse outcome, adjusted hazard ratio 0.86 (95% CI 0.79-0.94; P=0.0008).

Conclusions: The present study, by gathering a unique HCM cohort, suggests a strong link between LA dysfunction and poor outcome, to be further investigated.
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http://dx.doi.org/10.1016/j.acvd.2020.06.004DOI Listing
February 2021

Endometrioma ethanol sclerotherapy could increase IVF live birth rate in women with moderate-severe endometriosis.

PLoS One 2020 28;15(9):e0239846. Epub 2020 Sep 28.

Department of Obstetrics Gynecology and Reproductive Medicine, Pôle femmes parents enfants, IVF Unit/ CECOS, AP-HM La Conception University Hospital, Marseille, France.

Objective: To 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.

Methods: This 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.

Results: Seventy-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.

Conclusions: EST is an interesting technique to improve IVF success rates in women with moderate-severe endometriosis. EST could be discussed before IVF in infertile women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239846PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521758PMC
November 2020

Effect of early hyperoxemia on the outcome in servere blunt chest trauma: A propensity score-based analysis of a single-center retrospective cohort.

J Crit Care 2021 Jun 13;63:179-186. Epub 2020 Sep 13.

Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Nord Hospital, Department of Anesthesiology and Critical Care, Marseille, France.

Purpose: Our study aimed to explore the association between early hyperoxemia of the first 24 h on outcomes in patients with severe blunt chest trauma.

Materials And Methods: In a level I trauma center, we conducted a retrospective study of 426 consecutive patients. Hyperoxemic groups were classified in severe (average PaO ≥ 200 mmHg), moderate (≥150 and < 200 mmHg) or mild (≥ 100 and < 200 mmHg) and compared to control group (≥60 and < 100 mmHg) using a propensity score based analysis. The first endpoint was the incidence of a composite outcome including death and hospital-acquired pneumonia occurring from admission to day 28. The secondary endpoints were the incidence of death, the number of hospital-acquired pneumonia, mechanical ventilation-free days and intensive care unit-free day at day 28.

Results: The incidence of the composite endpoint was lower in the severe hyperoxemia group(OR, 0.25; 95%CI, 0.09-0.73; P < 0.001) compared with control. The 28-day mortality incidence was lower in severe (OR, 0.23; 95%CI, 0.08-0.68; P < 0.001) hyperoxemia group (OR, 0.41; 95%CI, 0.17-0.97; P = 0.04). Significant association was found between hyperoxemia and secondary outcomes.

Conclusion: In our cohort early hyperoxemia during the first 24 h of admission after severe blunt chest trauma was not associated with worse outcome.
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http://dx.doi.org/10.1016/j.jcrc.2020.09.008DOI Listing
June 2021

Influence of polycyclic aromatic hydrocarbon exposure on IVF: now is the time to focus on women.

Reprod Biomed Online 2020 Aug 28;41(2):161-169. Epub 2020 Apr 28.

Aix Marseille Univ, Avignon Université, CNRS, IRD, IMBE, Marseille, France; Laboratoire de Biologie de la Reproduction - CECOS, Pole Femmes-Parents-Enfants, AP-HM La Conception, Marseille, France.

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.
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http://dx.doi.org/10.1016/j.rbmo.2020.03.022DOI Listing
August 2020

Objective assessment of obstetrics residents' surgical skills in caesarean: Development and evaluation of a specific rating scale.

J Gynecol Obstet Hum Reprod 2021 Jan 19;50(1):101812. Epub 2020 May 19.

Department of Obstetrics and Gynecology, Nord Hospital, APHM, Chemin des Bourrely, 13015, Marseille, France; EA 3279, Public Health, Chronic Diseases and Quality of Life, Research Unit, Aix-Marseille University, 13284, Marseille, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jogoh.2020.101812DOI Listing
January 2021

Lower gestational age is associated with severe maternal morbidity of preterm cesarean delivery.

J Gynecol Obstet Hum Reprod 2020 Sep 23;49(7):101764. Epub 2020 Apr 23.

Department of Obstetrics and Gynecology, Nord Hospital, APHM, chemin des Bourrely, 13015, Marseille, France; EA3279, CEReSS, Health Service Research and Quality of Life Center, Aix-Marseille University, 13284, Marseille, France. Electronic address:

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 < 28 weeks and SMM (aOR, 1.80; 95 % CI, 0.99-3.27, p = 0.05).

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.
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http://dx.doi.org/10.1016/j.jogoh.2020.101764DOI Listing
September 2020

Left-ventricular non-compaction-comparison between different techniques of quantification of trabeculations: Should the diagnostic thresholds be modified?

Arch Cardiovasc Dis 2020 May 2;113(5):321-331. Epub 2020 Apr 2.

Cardiology Department, La Timone Hospital, AP-HM, 13005 Marseille France; Aix Marseille Université, IRD, APHM, MEPHI, IHU - Méditerranée Infection, 13005 Marseille, France. Electronic address:

Background: Diagnosis of left ventricular non-compaction (LVNC) is challenging, and different imaging techniques propose different criteria.

Aim: To compare the value of two-dimensional transthoracic echocardiography (2D-TTE) and cardiac magnetic resonance (CMR) criteria in diagnosing LVNC, and to test a new trabecular quantification method obtained by 2D-TTE, exploring its relationship with CMR non-compacted mass quantification.

Methods: From a multicentre French study, we selected 48 patients with LVNC and 20 with dilated cardiomyopathy (DCM) who underwent 2D-TTE and CMR. Current 2D-TTE (Jenni et al.) and CMR criteria (Petersen et al., Jacquier et al.), were tested. A new 2D-TTE method of trabecular quantification (percentage of trabecular area) was also proposed, and compared with current criteria.

Results: The best cut-off values for the diagnosis of LVNC were a non-compacted/compacted ratio≥2.3 (Petersen et al.), a trabeculated left ventricular mass≥20% (Jacquier et al.) and a non-compacted/compacted ratio≥1.8 (Jenni et al.). Lowering the threshold for the criterion of Jenni et al. from>2 to ≥1.8 improved its sensitivity from 69% to 98%. The 2D-TTE percentage of trabecular area was 25.9±8% in the LVNC group vs. 9.9±4.4% in the DCM group (P<0.05), and was well correlated with CMR non-compacted mass (r=0.65; P<0.05). A 15.8% threshold value for 2D-TTE percentage of trabecular area predicted LVNC diagnosis with a specificity of 95% and a sensitivity of 92%; its sensitivity was better than that for the criteria of Jenni et al. (P<0.01) and Petersen et al. (P=0.03).

Conclusions: Revision of the current threshold for the criterion of Jenni et al. from>2 to ≥1.8 is necessary to improve LVNC diagnosis in patients with left ventricular dysfunction. A new 2D-TTE trabecular quantification method improves TTE diagnosis of LVNC.
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http://dx.doi.org/10.1016/j.acvd.2020.01.004DOI Listing
May 2020

Lung Ultrasound Findings in the Postanesthesia Care Unit Are Associated With Outcome After Major Surgery: A Prospective Observational Study in a High-Risk Cohort.

Anesth Analg 2021 01;132(1):172-181

Department of Anesthesia and Intensive Care Medicine, and Centre d 'Investigation Clinique, Nord Hospital, Aix Marseille University, APHM, Marseille, France.

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 <2 hours after extubation, detection of immediate postoperative alveolar consolidation and pleural effusion by lung ultrasound is associated with postoperative pulmonary complications and morbi-mortality. Further study is needed to determine the effect of ultrasound-guided intervention for patients at high risk of postoperative pulmonary complications.
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http://dx.doi.org/10.1213/ANE.0000000000004755DOI Listing
January 2021

Health Status of French Young Patients with Inborn Errors of Metabolism with Lifelong Restricted Diet.

J Pediatr 2020 05 4;220:184-192.e6. Epub 2020 Mar 4.

Department of Epidemiology and Health Economics, AP-HM/EA 3279 CEReSS (Centre d'Etude et de Recherche sur les Services de Santé et la Qualité de vie), Aix-Marseille Univ, Marseille, France.

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.
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http://dx.doi.org/10.1016/j.jpeds.2020.01.059DOI Listing
May 2020

Learning Intracorporeal Suture on Pelvitrainer Using a Robotized Versus Conventional Needle Holder.

J Surg Res 2020 07 27;251:85-93. Epub 2020 Feb 27.

Department of Obstetrics and Gynecology, Assistance Publique - Hôpitaux de Marseille, La Conception Hospital, Aix Marseille Université, Marseille, France.

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.
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http://dx.doi.org/10.1016/j.jss.2020.01.016DOI Listing
July 2020

Specific cognitive correlates of the quality of life of extremely preterm school-aged children without major neurodevelopmental disability.

Pediatr Res 2020 10 12;88(4):642-652. Epub 2020 Feb 12.

EA3279, Self-Perceived Health Assessment Research Unit, Faculty of Medicine, Marseille, 13385, France.

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 (Vécu et Santé Perçue 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.
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http://dx.doi.org/10.1038/s41390-020-0795-8DOI Listing
October 2020

Femoral Versus Nonfemoral Peripheral Access for Transcatheter Aortic Valve Replacement.

J Am Coll Cardiol 2019 12;74(22):2728-2739

Department of Cardiology, La Cavale Blanche University Hospital Centre, Optimization of Physiological Regulations, Science and Technical Training And Research Unit, University of Western Brittany, Brest, France.

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.
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http://dx.doi.org/10.1016/j.jacc.2019.09.054DOI Listing
December 2019

Interest of IgG and IgM antiprothrombin autoantibodies in the exploration of antiphospholipid syndrome: a 5-year retrospective study.

Rheumatology (Oxford) 2020 07;59(7):1539-1544

AP-HM, Hôpital de la Conception, Pôle de Biologie, Service d'immunologie.

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.
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http://dx.doi.org/10.1093/rheumatology/kez453DOI Listing
July 2020

Speckle tracking quantification of lung sliding for the diagnosis of pneumothorax: a multicentric observational study.

Intensive Care Med 2019 09 29;45(9):1212-1218. Epub 2019 Jul 29.

Department of Anesthesiology and Intensive Care Medicine, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Hôpital Nord, Marseille, France.

Purpose: Lung ultrasound is used for the diagnosis of pneumothorax, based on lung sliding abolition which is a qualitative and operator-dependent assessment. Speckle tracking allows the quantification of structure deformation over time by analysing acoustic markers. We aimed to test the ability of speckle tracking technology to quantify lung sliding in a selected cohort of patients and to observe how the technology may help the process of pneumothorax diagnosis.

Methods: We performed retrospectively a pleural speckle tracking analysis on ultrasound loops from patients with pneumothorax. We compared the values measured by two observers from pneumothorax side with contralateral normal lung side. The receiver operating characteristic (ROC) curve was constructed to evaluate the performance of maximal pleural strain to detect the lung sliding abolition. Diagnosis performance and time to diagnosis between B-Mode and speckle tracking technology were compared from a third blinded observer.

Results: We analysed 104 ultrasound loops from 52 patients. The area under the ROC curve of the maximal pleural strain value to identify lung sliding abolition was 1.00 [95%CI 1.00; 1.00]. Specificity was 100% [95%CI 93%; 100%] and sensitivity was 100% [95%CI 93%; 100%] with the best cut-off of 4%. Over 104 ultrasound loops, the blinded observer made two errors with B-Mode and none with speckle tracking. The median diagnosis time was 3 [2-5] seconds for B-Mode versus 2 [1-2] seconds for speckle tracking (p = 0.001).

Conclusion: Speckle tracking technology allows lung sliding quantification and detection of lung sliding abolition in case of pneumothorax on selected ultrasound loops.
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http://dx.doi.org/10.1007/s00134-019-05710-1DOI Listing
September 2019

Training Organization, Physiological Profile and Heart Rate Variability Changes in an Open-water World Champion.

Int J Sports Med 2019 Aug 9;40(8):519-527. Epub 2019 Jul 9.

Fédération Française de Natation, Seine Saint-Denis, Pantin, France.

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 V̇O: 58.5 ml·min·kg, maximal heart rate: 178 beats per minute, and maximal ventilation: 170 L·min. Weekly training volume was 85±21 km, 39±8% was at [La]<2 mmol · L (Z1), 53±8% was at [La] 2-4 mmol·L (Z2), and 8±4% was at [La]>4 mmol·L (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.
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http://dx.doi.org/10.1055/a-0877-6981DOI Listing
August 2019

Common Risk Factors Add to Inherited Thrombophilia to Predict Venous Thromboembolism Risk in Families.

TH Open 2019 Jan 28;3(1):e28-e35. Epub 2019 Jan 28.

Laboratory of Haematology, La Timone Hospital, Marseille, France.

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 _rs2036914 and _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.
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http://dx.doi.org/10.1055/s-0039-1677807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524901PMC
January 2019

Progenitor mast cells and tryptase in Q fever.

Comp Immunol Microbiol Infect Dis 2019 Jun 20;64:159-162. Epub 2019 Mar 20.

Aix-Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France; APHM, IHU Méditerranée Infection, UF Immunologie, Marseille, France.

Q fever is an infectious disease due to Coxiella burnetii. Following a primary-infection, C. burnetii may persist in some patients, leading to endocarditis and vascular infections. Mast cells (MCs), known for their role in allergic diseases, innate immunity and cardiac function, are produced by bone marrow, circulate as progenitors in the bloodstream and reach tissues for their maturation and activation. The latter may be estimated by measuring serum tryptase levels. We wondered if MC progenitors and tryptase were affected in Q fever. We showed a decrease in MC progenitor count in Q fever patients whereas serum tryptase levels were increased. Taken together, our results show alterations of MC numbers and activity in Q fever patients, suggesting that MC are involved in Q fever pathophysiology.
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http://dx.doi.org/10.1016/j.cimid.2019.03.011DOI Listing
June 2019

High incidence of atrial fibrillation in patients treated with ibrutinib.

Open Heart 2019;6(1):e001049. Epub 2019 May 8.

Department of Cardiology, Unit of Heart Failure and Valvular Heart Diseases, Mediterranean University Cardio-Oncology Center (MEDI-CO Center), Hôpital Nord, Aix-Marseille I University, Marseille, France.

Objective: Atrial 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.

Methods: A 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.

Results: 53 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 (p<0.0001). The majority of cases occurred in asymptomatic patients within the first 6 months. Left atrial volume index ≥40 mL/m 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.

Conclusions: This 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.
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http://dx.doi.org/10.1136/openhrt-2019-001049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519413PMC
May 2019

Dynamic iron status after acute heart failure.

Arch Cardiovasc Dis 2019 Jun - Jul;112(6-7):410-419. Epub 2019 Apr 18.

Heart Failure and Valvular Heart Disease Unit, Mediterranean University Cardio-Oncology (MEDI-CO) Centre, Department of Cardiology, Aix-Marseille University, hôpital Nord, AP-HM, chemin des Bourrely, 13015 Marseille, France; Inserm 1263, INRA, centre de recherche cardiovasculaire et nutrition (C2VN), Aix-Marseille University, 13385 Marseille, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.acvd.2019.02.002DOI Listing
December 2019

Preliminary results of synergy between norepinephrine and terlipressin during septic shock.

Intensive Care Med 2019 05 6;45(5):730-732. Epub 2019 Feb 6.

Service d'Anesthésie et de Réanimation, Department of Anesthesiology and Intensive Care, Hôpital Nord, Assistance Publique Hôpitaux de Marseille, Aix Marseille Université, Chemin des Bourrely, 13015, Marseille, France.

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http://dx.doi.org/10.1007/s00134-018-05514-9DOI Listing
May 2019

Association between gestational age and severe maternal morbidity and mortality of preterm cesarean delivery: a population-based cohort study.

Am J Obstet Gynecol 2019 04 8;220(4):399.e1-399.e9. Epub 2019 Jan 8.

Department of Obstetrics and Gynecology, Nord Hospital, APHM, Marseille, France; EA 3279, Public Health, Chronic Diseases and Quality of Life, Research Unit, Aix-Marseille University, Marseille, France.

Background: 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.

Objective: The aim of this study was to evaluate whether gestational age <26 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.

Materials And Methods: 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 age <26 weeks and SMMM, we used multivariate logistic regression and a propensity score-matching approach.

Results: 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 age <26 weeks vs 376 (14.2%) between 26 and 34 weeks (P < .001). Cluster multivariate logistic regression showed significant association of gestational age <26 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).

Conclusion: 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.
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http://dx.doi.org/10.1016/j.ajog.2019.01.005DOI Listing
April 2019