French Centers Research Articles

Impact of transfusion on platelet aggregation and biomarkers in myocardial infarction patients with anemia: an ancillary study of the randomized REALITY trial

Abstract Importance Higher rates of thrombotic events have been reported in patients with myocardial infarction (MI) requiring blood transfusion. The impact of transfusion strategies on biomarkers of thrombosis and inflammation is still unknown. Objective Compare the impact of a liberal vs a restrictive transfusion strategy in anemic MI patients on P2Y12 mediated platelet reactivity and biomarkers of thrombosis and inflammation. Design and Setting: Prespecified ancillary study of the multicentric randomized REALITY trial, performed in 6 French centers between February 2018 and September 2019 (Figure). Patients randomized to a liberal (hemoglobin ≤10g/dL) or a restrictive (hemoglobin ≤8g/dL) transfusion strategy had platelet reactivity measured at baseline and after randomization. Participants: One hundred anemic acute MI patients from the REALITY trial (666 randomized patients). Measurements: Measurements of platelet reactivity included a centralized blinded VASP-PRI assay and PRU measured locally using encrypted VerifyNow assay. Biomarkers of thrombosis (P-selectin, PAI-1, vWF) and inflammation (TNF-α) were also measured. The primary endpoint was the change in the VASP-PRI (difference from baseline and post randomization) between the two randomized groups. Results Among 100 patients included (n=50 in each group), the most frequent P2Y12 inhibitors used was clopidogrel (48%) while 16% of the patients did not receive any P2Y12 inhibitors. Transfused patients received on average 2.4±1.6 units of packed red blood cells. We found no differences between groups in change in P2Y12-mediated platelet aggregation before and after randomization, measured either by the VASP PRI (difference 4.3%; 95% CI (-5.4% to 14.1%)) or by the PRU (difference 23.5; 95% CI (-20.8 to 67.8)). Similar results were found in transfused patients (n=71) regardless of the randomized group, VASP PRI (difference 1.6%; 95% CI (-6.7% to 10.0%)) or PRU (difference -17.6; 95% CI (-41.0 to 5.7)). We did not find an impact of transfusion strategy or transfusion itself in the levels of P-selectin, PAI-1, vWF and TNF-α. Conclusion and Relevance A liberal or a restrictive transfusion strategy does not impact platelet reactivity and biomarkers in MI patients with anemia, supporting the lack of clinically relevant difference in thrombotic risk between both strategies.

Impact of the antiplatelet strategy following patent foramen ovale percutaneous closure

Abstract Background Temporary dual antiplatelet therapy (DAPT) is recommended following patent foramen ovale (PFO) percutaneous closure although its benefit, compared to single antiplatelet therapy (SAPT), has not been demonstrated in this setting. Objective We aimed at assessing outcomes following PFO closure according to the antiplatelet strategy at discharge. Methods The ambispective AIR-FORCE cohort included consecutive patients from 7 centers in France and Canada undergoing PFO closure and discharged without anticoagulation. Patients treated in French and Canadian centers were mostly discharged with DAPT and SAPT, respectively. The primary endpoint was the composite of death, stroke, transient ischemic attack, peripheral embolism, myocardial infarction, or BARC type ≥2 bleeding with up to 5 years of follow-up. The impact of the antiplatelet strategy on outcomes was evaluated with a marginal Cox model (cluster analyses per country) with inverse probability weighting according to propensity score. Results A total of 1,532 patients were included from 2001 to 2022, of whom 599 (39.1%) were discharged with SAPT and 933 (60.9%) with DAPT, for ≤3 months in 894/923 (96.9%) cases (Table 1). After a median follow-up of 2.4[1.1-4.4] years, a total of 58 events were observed. In the weighted analysis the rate of the primary endpoint up to 5 years was 7.8% in the SAPT strategy and 7.3% in the DAPT strategy (weighted hazard ratio 1.04, 95% confidence interval 0.59-1.83) (Figure 1). Results were consistent in a sensitivity analysis. Conclusion The strategy of antiplatelet strategy following PFO closure did not seem to impact clinical outcomes, thus challenging the current recommendations of temporary DAPT.Table 1.Baseline characteristicsFigure 1.Central illustration

Machine learning to detect recreational drugs use in cardiac intensive care units

Abstract Background While recreational drugs use is known to be a strong risk factor of acute cardiovascular events, there is no available prediction tool to detect it in patients admitted to intensive cardiac care units (ICCU), and urinary testing is not routinely performed. Machine learning (ML) methods could provide an accurate model for detection of recreational drugs use. Purpose To assess the feasibility of recreational drugs use detection in patients admitted to ICCU using a ML model with clinical, biological, ECG, and echocardiographic data. Methods From 7 to 22 April 2021, a systematic screening for all traditional recreational drugs (cannabis, opioids, cocaine, amphetamines, 3,4-methylenedioxymethamphetamine [MDMA]) was performed by urinary testing prospectively in all consecutive patients admitted to ICCU in 39 French centres. We compared several ML algorithms to detect recreational drugs use from clinical, biological, ECG and echocardiographic data. The study population was divided in an internal (31 centres, 80% of the population) and an external (8 centres, 20% of the population) cohorts. The internal cohort was divided in a training (70% of the cohort) and a testing (30% of the cohort) dataset. XGBoost algorithm was used for feature selection to avoid overfitting, and gain interpretability. Final performance of the algorithms were evaluated on the external validation cohort and compared against a standard logistic regression model, using receiver operating characteristics (ROC) and precision-recall (PR) curves and area-under-the curves (AUC). Results Of 1,499 consecutive included in the cohort (63±15 years, 70% male), 161 (11%) had a positive test for recreational drugs (cannabis: 9.1%, opioids: 2.1%, cocaine: 1.7%, amphetamines: 0.7%, MDMA: 0.6%, Figure 1). Of the patients with a positive test, only 57% reported using recreational drugs. Out of 165 clinical, biological, ECG, and echocardiographic features, 9 variables were selected as being the most important in detecting drugs use: age, systolic pulmonary artery pressure, body mass index, hemoglobin, NT-pro BNP, temperature, active smoker status, heart rate, and mean blood pressure. The random forest model showed the best performance compared with the other ML models (AUROC=0.82; and PR-AUC=0.62, Figure 2), and with a traditional model using logistic regression (AUROC 0.82 vs. 0.80, and PR-AUC 0.62 vs 0.46; both p<0.001) to detect recreational drugs use. The random forest model also exhibited a good performance for detecting recreational drugs use in the external validation cohort (AUROC=0.76 and PR-AUC=0.44). Conclusions In a large ICCU registry, our ML algorithm including clinical, biological, ECG and echocardiographic data exhibited a higher performance to detect recreational drugs use than traditional statistical methods. Knowing the high rate of underreporting in this study, it is crucial to validate the performance of this ML tool in further larger studies.Model developmentModel performances

Standard modifiable risk factors and mortality in patients with ST-segment elevation myocardial infarction: findings from the FRENCHIE cohort

Abstract Background Improvements in the treatment of the 4 main standard modifiable cardiovascular (CV) risk factors (SMuRFs), hypertension (HTN), diabetes, hypercholesterolemia, and smoking, have led to better survival in patients with acute myocardial infarction (AMI). Recent large observational studies have reported that an increasing and sizable proportion of AMI patients have no SMuRF, and these SMURFless patients have (counterintuitively) worse outcomes than patients with at least one SMuRF. Purpose Using a French nationwide MI registry, we aimed to describe the proportion, characteristics and in-hospital mortality of ST-segment elevation MI (STEMI) patients according to the burden of SMuRFs. Methods The French Cohort of Myocardial Infarction Evaluation (FRENCHIE) is a large ongoing MI cohort, which collects data from all patients hospitalized for AMI < 48 h of symptom onset in 21 french centres. For the present analysis, patients with STEMI and without prior coronary artery disease (CAD) admitted in 2019 and 2020 were studied. SMuRFless patients were compared to patients with 1 SMuRF or ≥2 SMuRFs. Results Among 4692 STEMI patients, 986(21%) were SMuRFless, 2001(43%) had 1 SMuRF, and 1705(36%) had ≥2 SMuRFs . Among patients with SMuRFs, smoking (51.8%) and HTN (51.1%) were the most frequent SMuRF and HTN+hypercholesterolemia (10.3%) and HTN+smoking (8.3%) the most frequent SMuRFs associations. When compared with patients with 1 or ≥ 2 SMuRFs, SMuRFless patients were characterized by older age (64.1 vs 60.2 and 62.8 y, respectively), but lower rate of female sex (21.7 vs 22.2 and 26.2%, respectively), LVEF<40% (24.5 vs 26.7 and 26.2%), and lower admission CRP (14.8±38.3 vs 15.3±38.7 and 17.3±40.1 mg/L, respectively). There was a slight increase in BMI with increasing SMURFs (0 SMURF : 26±3.9 ; 1 SMuRF : 26.3±4.5 ; ≥2 SMuRFs : 28.0±5 kg/m²). As expected, SMuRFless patients were less frequently under chronic CV medications (7.9 vs 23.5 and 57.7%, respectively). However, acute STEMI medications were similar across the 3 groups. Crude in-hospital mortality showed a trend toward an increase with the number of SMuRFs (p = 0.123). By multivariate logistic regression analysis, the number of SMURFs was associated with increasing in-hospital mortality (Figure). In stratified analyses, the odds were similar for both sexes. Conclusion In French patients with an inaugural STEMI, one in 5 patient was SMURFless. The burden of risk factors was independently correlated to worse in-hospital survival. These observations emphasize the importance of standard RF on acute MI outcomes.SMuRF and in-hospital death(forest plot)

The HFA PEFF diagnostic algorithm poorly correlates with invasive LV filling pressure in HF PEF

Abstract Background Heart failure with preserved ejection fraction (HFPEF) patients typically have elevated LV filling pressures, whether at rest and/or on exercise. In 2020, the HFA-ESC proposed a process to detect HFPEF called HFA–PEFF diagnostic algorithm, which has not been validated against invasive right heart catheterization (RHC). Purpose The purpose of this work was to compare this algorithm against LV filling pressures invasively calculated. Methods PH-HF registry enrolled 663 patients with HF from which 276 had preserved ejection fraction with and without pulmonary hypertension explored at 11 French centres between 2011 and 2021. Patients meeting the 2021 ESC definition of heart failure underwent both RHC at steady state under optimal medical therapy and a complete ultrasound study within 24 hours. From 4 domains, the HFA–PEFF score was calculated with the use of major and minor criteria. A score ≥5 points is considered to be diagnostic, while between 2-4, further investigations are requested. The score was compared to pulmonary wedge pressure. Results Mean age age was 69,5±12.4 years, 35,1% male, mean left ventricular ejection fraction was 62,5±7,2%. Wedge pressure was 20,5±7,5 mm Hg and HFA-PEFF score averaged 4,9±1,2 with 181 patients (66%) above 5. Sensitivity and specificity were 68% and 46%, respectively. The figure 1 demonstrates the misclassification of patients, particularly those with high HFA-PEFF score but normal left ventricular filling pressure (lower right), that are badly categorized. Conclusions The HFA-PEFF score poorly correlates with invasive measurement of LV filling pressure. Patients with high score may require more careful attention as they are often misclassified.Figure 1

Neuropsychological assessment in pediatric epilepsy surgery: A French procedure consensus

Neuropsychological assessment is a mandatory part of the pre- and post-operative evaluation in pediatric epilepsy surgery. The neuropsychology task force of the ILAE - French Chapter aims to define a neuropsychological procedure consensus based on literature review and adapted for French practice. They performed a systematic review of the literature published between 1950 and 2023 on cognitive evaluation of individuals undergoing presurgical work-up and post-surgery follow-up and focused on the pediatric population aged 6–16. They classified publications listed in the PubMed database according to their level of scientific evidence. The systematic literature review revealed no study with high statistical power and only four studies using neuropsychological scales in their French version. Afterwards, the experts defined a neuropsychological consensus strategy in pediatric epilepsy surgery according to the psychometric determinants of cognitive tests, specificity of epilepsy, surgery context, French culture and literature reports. A common French neuropsychological procedure dedicated to pediatric epilepsy surgery is now available. This procedure could serve as a guide for the pre- and post-surgical work-up in French centers with pediatric epilepsy surgery programs. The main goal is to anticipate the functional risks of surgery, to support the postoperative outcome beyond the seizure-related one, while taking into consideration the plasticity and vulnerability of the immature brain and allowing the possibility of collaborative studies.

État des lieux en 2023 du registre France PCI

The French PCI Registry collects up to 150 clinical, procedural, and one-year follow-up data on all coronary angiographies and angioplasties performed in the 61 participating centers in September 2023. Thanks to the support of the GACI, the DGOS, the ARS, and numerous hospitals, the registry is continuing to expand its coverage across the entire territory, with 90 centers expected to participate in 2024, accounting for nearly half of the French centers. The high quality of this data has already led to the publication of 18 studies in international journals, and around twenty others are currently being written. The online publication of comprehensive and comparative annual reports, along with the implementation of quality indicators to assess practices, would enhance the performance of all participating centers and ultimately benefit our coronary patients.

Abstract 11958: Incidence and Predictors of In-Hospital Complications After Myocardial Infraction in Contemporary Clinical Practice: Findings From the FRENCHIE Myocardial Infarction Cohort

Introduction: It is important to identify patients presenting with myocardial infarction eligible for early hospital discharge in order to avoid prolonged hospitalizations and reduce costs. Hypothesis: From a contemporary French nationwide MI cohort, we aimed to analyze incidence and correlates of in-hospital MI complications. Methods: French Cohort of Myocardial Infarction Evaluation (FRENCHIE) is a large ongoing MI registry, which collects data from all patients admitted for MI < 48h of symptom onset in 21 French centers. In-hospital complications were collected and patients who experienced complications were compared to those who did not. Results: Overall, 9692 patients presenting with MI were enrolled (5325 STEMI (55%) and 4367 NSTEMI). Among these, 2755 (28%) presented at least one complication during hospitalization. The median length of stay was 4 days [3-7]. The complications were: high degree AV block (2.4%), atrial arrhythmias (7.7%), ventricular arrhythmias (5%), reinfarction (including stent thrombosis) (0.9%), stroke (0.6%), mitral valve and chordae rupture/tear (1.4%), ventricular free wall rupture (0.1%), ventricular septal defect (0.2%), tamponade (0.2%), heart failure (Killip class >1) (15.4%) including cardiogenic shock (3.2%) and need for assistance (1.3%), LV thrombus (1.5%), acute renal failure (4.2%), major bleeding (0.7%) and in-hospital death (2.9%). Independent predictors of the absence of any complications were: younger age (OR=0.97 and 95%CI=[0.96-0.97]), absence of PAD (1.4 [1.2-1.8]), absence of AF (2 [1.6-2.5], absence of HF (2.3 [1.7-3.1]), presentation as NSTEMI (as compared to STEMI) (1.6 [1.4-1.8]), successful PCI (0.6 [0.5-0.7]), heart rate (0.98 [0.98-0.99]), systolic blood pressure (1.01 [1.00-1.01]), creatinine (0.98 [0.97-0.99]), hemoglobin (1.06 [1.03-1.10]), leucocytes (0.94 [0.93-0.96]) and CRP (0.99 [0.99-1.00]). Conclusions: In-hospital complications after MI are still frequent (more than 1/4 of patients) and driven by atrial arrhythmias and heart failure. Patients presenting with inaugural NSTEMI successfully revascularized, with no history of cardiovascular disease, and normal heart rate, systolic blood pressure and biology parameters may be targeted for early discharge.

Abstract 14994: A Propensity Score Analysis of Early and Long-Term Outcomes After Ticagrelor or Clopidogrel in Elderly Patients With Acute Myocardial Infarction: The Fast-MI 2015 Registry

Introduction: Guidelines recommend ticagrelor (T) over clopidogrel (C) in AMI patients, irrespective of age. Real-world evidence in the very elderly is limited. Question: Whether T is superior to C for elderly patients regarding early and long-term outcomes in real-life conditions. Goal: To analyze in-hospital, one- and 5-year outcomes according to use of T or C in AMI patients ≥80 yo. Methods: FAST-MI 2015 included consecutive AMI patients over 1 month in 204 French centers. Patients ≥80 yo, receiving C or T ≤48 hours of admission were studied. Propensity scores (PS) for receiving T or C was used in multivariable analyses and for PS matching. Results: Of 5291 patients in the registry, 995 (19%) were ≥80 yo, of whom 870 (87%) met the inclusion criteria. Mean age was 85±4 years (86 ± 4 for C-treated; 84±3 for T-treated), 51% were women (50.5% and 53% respectively for C and T), and 40% had STEMI (33% and 49% respectively). PS-adjusted HRs for T vs C were 1.26, 95%CI 0.65-2.44 for 30-day death, 1.09, 95% CI 0.71-1.67 for death at one year and 0.86, 95% CI 0.67-1.11 at 5 years. After PS matching, the two cohorts (N=293 each) were well balanced for all baseline characteristics including medications given at the acute stage. In-hospital complications, including major bleeding, re-MI, stroke and death were similar for T and C. Thirty-day, one-year, and 5-year mortality were similar for the 2 medications, with a trend favouring T over time, suggesting the possibility of undetected confounders (Figure). In hospital survivors, however, T at discharge was associated with improved 5-year survival (PS-adjusted HR 0.64, 95%CI 0.46-0.90), compared with C. Conclusions: In this real-world population of elderly (mean age 85 years) patients with AMI, initial use of ticagrelor was not associated with improved survival, compared with clopidogrel. In hospital survivors, however, ticagrelor at discharge was associated with reduced long-term mortality.

French Interventional Radiology Centers' Uptake of Transradial Approach and Outpatient Hepatocellular Carcinoma Intra-Arterial Treatments.

This study aims to investigate the uptake of transradial approach (TRA) and outpatient setting for transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) in the treatment of hepatocellular carcinoma (HCC) among French interventional radiology centers. This cross-sectional study was based on a 34-question survey assessing center activity, radial access, and outpatient care. The survey was developed by a working group, tested by two external experts, and distributed to active members of two French radiological societies via a web-based self-reporting questionnaire in March 2022. The survey remained open for eight weeks, with two reminder emails sent to non-responders. Only one answer per center was considered. Of the 44 responding centers, 39% (17/44) performed TRA for TACE and/or TARE, with post-procedure patient comfort as main motivation. Among the 27 centers not performing TRA, 33% (9/27) reported a lack of technical experience, but all 27 intended to adopt TRA within two years. Only six centers performed TACE or TARE in an outpatient setting. Reasons limiting its implementation included TACE for HCC not being a suitable intervention (61%, 27/44) and organizational barriers (41%, 18/44). Among centers not performing outpatient TACE or TARE, 34% (13/38) said "No," 34% (13/38) said "Maybe," and 32% (12/38) said "Yes" when asked about adopting it within two years. French interventional radiologists have low TRA uptake for HCC treatment, but TRA adoption potential exists. Respondents were uncertain about performing TACE or TARE in an outpatient setting within a 2-year horizon.

Efficacy of Chemo-Free Combination Therapy with BRAF Inhibitor and Rituximab in Classic Hairy Cell Leukemia: Insights from the French Experience

Background: Hairy cell leukemia (HCL) is a rare form of leukemia. The introduction of purine analogs has revolutionized its prognosis, leading to a life expectancy closer to that of the general population. However, patients experience relapses and require other treatment options. The BRAF V600E mutation is present in 80-100% of patients with HCL, which has prompted the use of BRAF inhibitors (vemurafenib or dabrafenib) in this condition. Recently, the combination of vemurafenib with rituximab has shown efficacy with durable responses in relapsed patients. Here, we present, for the first time, real-life data on the combination of a BRAF inhibitor with rituximab through a retrospective study involving 9 French centers. Data collection was completed by July 1, 2023. Results: We collected data from 17 patients with a male-to-female ratio of 13:4; the median age was 69 years (38-90), and 6 patients were aged over 75. The median number of previous treatments was 4 (0-7), and 3 patients were treatment-naive because they were deemed ineligible for purine analogs based on age or performance status. All 14 relapsed patients had previously received purine analogs once or multiple times (1-3). The median progression-free survival (PFS) after purine analogs was 48 months, and the median PFS after the last line of therapy was 24 months. Five patients were exposed to moxetumumab pasudotox, and 3 patients received single-agent vemurafenib previously. The BRAF V600E mutation was tested and positive for 16 patients. In our cohort, 13 patients received a combination of vemurafenib with rituximab (V+R), and 4 patients received a combination of dabrafenib with rituximab (D+R). All patients received the same regimen (Tiacci, NEMJ 2021), which included an induction phase (V+R or D+R for 8 weeks) followed by rituximab consolidation (4 injections every 15 days), except for one patient who received a rituximab sequence followed by vemurafenib. At the time of analysis, 15 out of 17 patients had completed the treatment, and the remaining 2 had completed the induction phase. Fourteen patients initiated treatment at the standard dose (960 mg bid for vemurafenib and 150 mg bid for dabrafenib), and 3 patients at a reduced dose (240-480 mg bid for vemurafenib). Toxicity of any grade was reported in 15 out of 17 patients, with 3 of them experiencing grade 3-4 toxicity. Skin toxicity was the most frequent, recorded in 12 patients (grade 1-2), leading to temporary treatment interruption in 2 patients and dose reduction in 6 patients. Other toxicities included musculoskeletal, hepatic, hematological, and cardiac, with only one patient experiencing a grade 2 infection during treatment. No secondary cancers were reported during or after treatment. Treatment was discontinued due to toxicity in 5 patients, with 4 of them resuming treatment later. Eight patients required a dosage reduction, with a median final vemurafenib dosage of 480 mg bid. At the end of treatment, 14 patients achieved a complete hematological response, and 1 patient achieved a partial response. Among the 9 patients with early response data, the median time for platelet recovery was 15 days, and for neutrophil recovery, it was 14 days. End-of-treatment bone marrow aspiration and/or biopsy was performed for 8 patients, showing a complete response in 7 patients. With a median follow-up of 12 months (4-56), only 2 patients had progressed, and as of the last update, no patients had died, and the 2 relapsed patients achieved a complete response after a new line of therapy. Conclusion: Despite a limited median follow-up of 12 months, the combination of a BRAF inhibitor with rituximab proves to be an effective regimen in heavily treated patients with HCL, achieving a 100% overall response rate. Our study confirms a rapid hematological response and an acceptable toxicity profile, even in elderly patients. The most frequent toxicity observed was cutaneous toxicity, mainly grade 1-2, and it never led to a definitive treatment discontinuation. A comparison of the two BRAF inhibitors in terms of efficacy or toxicity cannot be established due to the small sample size of patients treated with dabrafenib. Lastly, the combination of rituximab with vemurafenib or dabrafenib appears to be an interesting option in frontline treatment for patients ineligible for purine analogs.

Real World Data of Axicabtagene Ciloleucel As Second Line Therapy for Patients with Large B Cell Lymphoma: First Results of a Lysa Study from the French Descar-T Registry

Background and Significance: Axicabtagene ciloleucel (axi-cel) has demonstrated superior efficacy as second-line therapy (2L) over standard of care chemo-immunotherapy in transplant-eligible patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). In ZUMA-7 trial, 180 patients were randomized to receive axi-cel in 2L, achieving an estimated 4-year overall survival of 54% after a median follow-up of 47 months. In the ALYCANTE phase II study, 62 transplant-ineligible patients with R/R LBCL were treated with axi-cel as 2L, resulting in a 3-month complete metabolic response rate of 71% with a median progression free survival of 11.8 months. Here, we report the first real-world data of axi-cel as 2L for patients with early R/R LBCL treated in French centers. Study Design and Methods: DESCAR-T is a French nationwide registry collecting real-life data of all patients treated with approved CAR T-cell therapies (NCT04328298). All patients were informed before inclusion in the registry. The goal of the present analysis was to describe patients' characteristics, treatment course, and outcomes of all patients consecutively included in DESCART registry since July 2022, and infused with axi-cel according to the early access program supported by French authorities for patients with LBCL in early relapse (< 1 year) or refractory after a first line treatment. Results: Between July 2022 and March 2023, axi-cel was ordered and leukapheresis was performed for 85 patients. The first axi-cel infusion was performed in September 2022 and enrollment increased rapidly with 51 new patients waiting for a leukapheresis at the time of data cut-off in March 2023. No manufacturing failures occurred, at the data cut-off, 78 patients were infused with axi-cel in 22 centers, and 7 patients died before axi-cel infusion (5 because of progression, 2 from other cause). Among the 78 patients infused, 48 (61.5%) were male, median age was 60 years (range: 23-79), 35% were over 65 years old and 5% over 70 years old. Most patients had primary refractory disease (n = 58, 74.3%), a good performance status (n = 62, 79.5% ECOG 0-1), stage III-IV disease (n = 59, 75.6%) and elevated LDH (n = 48, 61.5%). The median time between leukapheresis and axi-cel infusion was 36 days, and 65 patients (83%) received bridging therapy, primarily immuno-chemotherapy (n = 57, 73%). At the time of lymphodepletion, patients had progressive (n = 35, 54%) or stable disease (n = 6, 9%), with only 23 patients (29%) responding to bridging therapy. The median follow-up since CAR-T-cells infusion was 1.1 month (range: 0-6). Safety information was reported for 65 patients: CRS occurred in 95% of patients, however only 3 patients (<5%) had a grade 3 or higher CRS. Neurotoxicity occurred in 43% of the cases, with 6 patients (9%) presenting grade 3 or higher toxicity. Furthermore, 13 patients (21%) were transferred to intensive care unit. Four patients (5%) died, 3 from lymphoma progression (missing data for the remaining patient). Among the 52 patients with at least 1 month of follow-up: the overall response and complete response rates at 1 month were 76.9% and 57.7% respectively (Figure 1). Conclusion: These preliminary results demonstrated that axi-cel in 2L for R/R LBCL is feasible and safe in real-life for transplant and non-transplant eligible patients. Although follow-up of our population remains short, early assessments of response are in line with those described in ZUMA-7 study. Inclusion in DESCART registry is on-going and updated results with at least 3 months of follow-up since infusion will be presented at the meeting.

Combination Chemotherapy in Patients with Newly Diagnosed Blastic Plasmacytoid Dendritic Cell Neoplasms (BPDCN): First Results of a Prospective French Trial (LpDessai)

Introduction Blastic plasmacytoid dendritic cell neoplasms (BPDCN) are now well-characterized diseases clearly referenced in the 5 th edition of the World Health Organization (WHO) Classification of Tumors (2022) 1 but treatment remains a real challenge. There is no consensus on the first line treatment even if CD123 targeted therapies are available in the USA and some European countries. Standard chemotherapy remains largely used as first line treatment with better results of leukemia-based regimens despite a high toxicity rate in this frail population 2,3. To establish a reference chemotherapy scheme, we prospectively evaluated the efficacy and toxicity of a combination chemotherapy (idarubicin, methotrexate, L-asparaginase, and dexamethasone) in newly diagnosed BPDCN patients (pts) in France. Patients and methods This single stage phase II study enrolled consecutive adult pts with suspected BPDCN in participating French centers. BPDCN diagnosis was centrally reviewed for cytology and immunophenotype (IF) (Pr Garnache Ottou F, UMR RIGHT BESANCON) and if needed for histology (Dr Petrella T, Montréal, Canada) according to published recommendations 1,4. After giving their informed consent, patients were evaluated for tumoral involvement by PET-scan, systematic lumbar puncture, and the mSWAT score was calculated for skin extension. Patients then received three 21 days-cycles of Ida/Metho/L-asp/Dex combination, before evaluation. Eligible patients with complete response (CR), complete response with incomplete bone marrow recovery (CRi) or partial response (PR) underwent allogeneic hematopoietic stem cell transplantation (HCT). Those not eligible received consolidation chemotherapy with 28 days cycles of Metho/L-asp/Dex (Figure 1). The primary objective was the proportion of patients with CR after 3 cycles of chemotherapy. Secondary objectives were the proportion of patients with an objective response (ORR) defined as CR, CRi or PR, the minimal residual disease (MRD) in responding patients evaluated by the presence of plasmacytoid dendritic cell blast measured by flow cytometry in the bone marrow, the incidence of severe adverse events and overall survival (OS). The competent ethics committee (Comité de Protection des Personnes Île de France 8) approved the study. The Besançon University hospital promoted the trial, financed by a grant of the French National Cancer Institute (INCa-DGOS_11093). Results Twenty-eight pts, originating from 16 centers, were screened between May 2019 and March 2023. Two patients with a misdiagnosis were screen failures. Two patients did not receive the planned chemotherapy due to clinical deterioration; 24 patients (21 male, 3 female) received at least one chemotherapy cycle and 23 are analyzed with a current end-point on June 30, 2023. Median age was 65y (21-79y). ECOG status was 0-1 in 20 cases, and 2 in 3 cases. A cutaneous involvement was identified in 16 pts (70%) and an extra medullary involvement was present in 13 (62%) pts: spleen, n= 6 (25%); lymph nodes, n= 7 (30%). Twenty-three pts (90%) had a bone marrow infiltration (identified only on IF in 4 cases), and 3 cases (14%) a documented central nervous system involvement. Nine pts had to stop planned treatment due to severe adverse events (3 deaths, 4 acute renal failure and 2 grade 4 febrile neutropenia) and in 4 pts, at least one cycle had to be delayed. Among the 15 pts receiving at least 3 cycles, 12 (80% and 50% of the whole cohort) were in ORR (CR = 8, CRi = 2, PR = 2) after the 3rd cycle of chemotherapy, 2 pts did not respond. Eight of ten (80%) CR/CRi pts had a MRD < 10 -4 without any further relapse. Nine of 12 responding patients (75%) received an allogeneic HCT 1-2 months after the end of the 3 rd cycle. Global OS at 6 months for responding or failing pts were 100% and 37% respectively (Figure 2). Conclusion In selected pts, an adapted chemotherapy could offer high CR rate in pts able to follow the planned treatment but remains toxic in frail pts, with only half of the them achieving a 3 rd cycle of chemotherapy. We confirm that pts achieving ORR and receiving HCT obtain prolonged CR. MRD level seems to correlate with OS and could be a useful tool to manage treatment toxicity in BPDCN frail pts.

Real-Word Experience of CAR T-Cells in Patients with Relapsed/Refractory Follicular Lymphoma : A Descart Registry Analysis from the Lysa

Background: Anti-CD19 CAR T-cells have revolutionized the treatment of aggressive B-cell non-Hodgkin lymphomas (NHL) by demonstrating durable responses. Although follow-up remain short, axicabtagene ciloleucel (axi-cel, ZUMA-5) and tisagenlecleucel (tisa-cel, ELARA) demonstrated promising complete response rates (CRR) of 86% and 69%, respectively, in phase II trials including relapsed or refractory (R/R) follicular lymphoma (FL).. Tisa-cel and axi-cel are now approved after at least 2 lines of systemic therapy by the FDA. Few real-word evidence (RWE) data have been reported so far. Methods: Patients were eligible if aged >18 years, had FL histology (grade 1-3A) and had received at least 2 previous treatment lines for tisa-cel and 3 for axi-cel according to the French early access program label. From Dec 2021 to Jan 2023, a total of 112 patients were included in early access program by 21 French centers and in DESCAR-T registry (NCT04328298), among them 87 were infused with a CAR product. At the data cut-off on March 2023, 70 had at least 1 month of follow-up (FU) with PET-CT evaluation, and thus were considered for the safety and efficacy sets (62 tisa-cel and 8 axi-cel,). Results: Patient and disease characteristics were as follows: 46 males (65.7%), median age 62 years (range: 34-79), 3 median prior lines of therapy (range 2-9, including bi-specific antibody in 12.9% and autoSCT in 44.3%), FLIPI 0-2 in 40.5% and 3-5 in 49.5%, bulky disease (>5cm) in 22%, and LDH > N 52.2%. POD24 after 1 st systemic immunochemotherapy (IC) was reported in 44 patients (62.8%). Before CAR T-cell infusion, 58.6% of patients received a bridging therapy (20 (48.8%) chemotherapy, 25 (61%) monoclonal antibodies, 4 (9.8%) kinase inhibitors, 15 (36.6%) lenalidomide, and 3 (7.3%) radiotherapy). All patients but one received a fludarabine and cyclophosphamide-based lymphodepletion. Median time from order to infusion was 48 days (range 34-204), and 41 days (30-328) from leukapheresis to infusion. Median FU was 7.3 months [6.4; 8.2] from product order, and 5.4 months [3.4; 6] from CAR infusion. Best ORR and CRR were 97.5 and 87.5%, respectively with 72.5% of patients in CR at 1 month with projected DOR and DOCR of 72.4% [56.8; 83.1%], and 79.7% [62.7%; 89.6%], respectively. Projected 6-months PFS, OS, were 71.8% [95% CI, 56.6%; 82.4%], 97.4% [83.2%; 99.6%], respectively. Fifteen (21.4%) patients progressed (median time from infusion to first relapse: 3 months (range 1-10 mo). Only one patient died from lymphoma progression. Any-grade CRS and ICANS were reported for 74.3% and 27.1% of patients, but grade 3-4 CRS/ICANS were very unfrequent,1.4% and 4.3%, respectively. No grade 5 was reported. Persisting grade 3-4 hematologic toxicities at 1 and 3 months were: neutropenia (50% and 12.3%), thrombocytopenia (18.6% and 0%), and anemia (8.6% and 0%). Medically relevant bacterial and viral infections were reported in 20% and 14.3% of patients, respectively. Conclusions: Although longer FU is needed to assess disease control, RWE data from the DESCAR-T registry confirm the excellent response rates and safety profile of CAR T-cells in R/R FL after at least 2 lines of previous therapy.

Prognostic impact of lymph node characteristics after therapeutic neck dissection for classic N1 papillary thyroid cancer.

The impact of lymph node characteristics on mortality and recurrence remains controversial. This study evaluated the prognostic impact of lymph node characteristics in a large, homogenous cohort of patients with therapeutic neck dissection for clinically N1 classic papillary thyroid cancer (PTC). All consecutive adult patients with therapeutic central and lateral neck dissection for PTC at a French referral centre were prospectively enrolled from January 2000 until June 2021. The primary outcome was the impact of lymph node characteristics in predicting a disease event (persistence or recurrence), using univariable and multivariable logistic regression modelling. A total of 462 patients were included. Lymph node capsular rupture was seen in 260 patients (56.3 per cent). Median maximum lymph node size was 15 (i.q.r. 9-23) mm. The median central, lateral, and total lymph node ratio (LNR) was 0.50 (i.q.r. 0.22-0.75), 0.15 (i.q.r. 0.07-0.29), and 0.26 (i.q.r. 0.14-0.41), respectively. After a median follow-up of 93 (i.q.r. 50-149) months, 182 (39.4 per cent) patients had a disease event. After multivariable analysis, the number of harvested lymph node >35 (OR 2.33 (95 per cent c.i. 1.10-4.95)), presence of lymph node capsular rupture (OR 1.92 (1.17-3.14)), and total LNR >0.20 (OR 2.37 (1.08-5.19)) and >0.40 (OR 4.92 (1.61-15.03)) predicted a disease event. An LNR of 0.20 predicted a disease event with a sensitivity of 80.8 per cent and a specificity of 50.4 per cent. Disease persistence or recurrence after thyroidectomy with therapeutic neck dissection for classic PTC with preoperative nodal disease appears to depend on number of harvested lymph node, presence of lymph node capsular rupture, and total LNR.

Registre national des dissections coronaires spontanées : le registre DISCO

AimSpontaneous coronary artery dissection (SCAD) is a form of acute coronary syndrome (ACS). The aim of this registry is to assess the clinical and angiographic features of SCAD, to describe the therapeutic management and prognosis, and to identify links with other vascular diseases. MethodFrom 2016 to 2018, 424 patients with a diagnosis of SCAD were included prospectively and retrospectively in 51 French cardiology centres. Results373 patients with confirmed SCAD were included. The mean age was 51.5±10.3 years with 90.6% women. 54.7% of patients had <2 cardiovascular risk factors. ACS occurred in 96.2% of patients. 84.2% of patients were managed conservatively, 15.5% interventionally and 0.3% surgically.At 1-year follow-up, recurrence of SCAD occurred in 3.3%. No deaths occurred.The association with fibro-muscular dysplasia was found in 45% of cases and genetic analysis confirmed a strong relationship between the occurrence of SCAD and gene variations at the PHACTR1 locus. ConclusionThe DISCO registry is the largest European cohort of SCAD. It confirms that this disease mainly affects young women with few cardiovascular risk factors, and that there is a strong association with the presence of fibromuscular dysplasia (45%). Conservative management should be preferred, with a favourable prognosis (no deaths at 1 year; recurrence rate of 3.3%).

Incidence of commuting accidents among non-physician staff in a large French university hospital centre from 2012 to 2016.

Traffic road crashes are the leading cause of fatal crashes at work. The circumstances of work-related road accidents have been a regular focus of study, but there is still a lack of knowledge about commuting accidents. The aims of this study were to estimate the overall incidence of commuting accidents for non-physician professionals in a major French university hospital, by gender and different professional categories, and to assess its evolution over a 5-year period. A descriptive analysis was performed on 390 commuting accidents from 2012 to 2016 extracted from the university hospital's occupational health service. Incidences of commuting accidents were calculated according to gender, occupational categories, and years. Crude relative risk (RR) for the association of commuting accidents with gender, occupational categories, and year of the accident was also estimated using log-binomial regressions. The annual incidence ranged from 354 to 581 accidents per 100,000 employees. Compared with administrative staff, the relative risk (RR) for commuting accidents for service agents was 1.6 (95% confidence interval (CI): 1.1-2.4) and for auxiliary nurses and childcare assistants was 1.3 (95% CI: 1.0-1.9). Nursing executives had a non-significantly lower RR of 0.6 (95% CI: 0.3-1.5). The increased risk observed for the auxiliary nurses and childcare assistants and for the service agents may be related in part to the fatigue caused by work schedules, long commuting distances, physical work, and psychological burden.

Real-life Perioperative Outcomes of Radical Prostatectomy using the French National Registry: A Plea for Promotion of Centralized Care and Access to Minimally Invasive Approaches

Radical prostatectomy (RP) can be performed using an open (ORP), laparoscopic (LRP) or robotic (RARP) approach. Most studies, even in experienced centers, have not provided solid evidence demonstrating better outcomes when using the robotic approach. In addition, one of the remaining concerns about RARP is its cost effectiveness, leading to no reimbursement for this surgical technique in some countries and thus health care inequality. We used data from a French national registry to improve knowledge of RP outcomes in a real-world scenario in order to guide and inform health care decision-makers. A total of 21 213 RP procedures were performed in 645 French centers in 2021 (ORP 20%, LRP 25%, and RARP 55% of cases). ORP was associated with longer hospital stay (p < 0.001), higher rates of postoperative complications (p < 0.001), fewer days out of hospital within 90 d of surgery (81.7 vs 83.6 vs 84.9 d for ORP vs LRP vs RARP; p < 0.00), and higher hospitalization costs (€2424 vs €1789 vs €1302). RARP is an optimal and cost-effective approach, with several advantages over ORP. Our data can be used by health care decision-makers to facilitate access to and reimbursement for the robotic approach for RP indications. Patient summaryFor men with prostate cancer for whom surgery is recommended, surgeons can remove the prostate using open surgery or a keyhole approach with or without robot assistance. Open surgery has higher costs, more complications, and longer hospital stays.

Frequency and predictors of decompressive craniectomy in ischemic stroke patients treated by mechanical thrombectomy in the ETIS registry

Background and aimsMechanical thrombectomy (MT) for patients with acute ischemic stroke (AIS) is usually performed in a comprehensive stroke center with on-site neurosurgical expertise. The question of whether MT can be performed in a primary stroke center without a neurosurgical facility is debated. In this context, there is a need to determine the frequency, delay and predictors of neurosurgical procedures in patients treated by MT. This study aims to determine these factors. MethodsIn total, 432 patients under 60years old, diagnosed with an acute ischemic stroke with a large vessel occlusion and treated by MT between January 2018 and December 2019 in six French stroke centers, were selected from the French clinical registry ETIS. Univariate and multivariate logistic regression models were used to identify predictive factors for decompressive craniectomy. ResultsAmong the 432 included patients, 43 (9.9%) patients with an anterior circulation infarct underwent decompressive craniectomy. Higher admission NIHSS (OR: 1.08 [95% CI: 1.02–1.16]), lower ASPECT (OR per 1 point of decrease 1.53 [1.31–1.79] P<0.001) and preadmission antiplatelet use (OR: 3.03 [1.31–7.01]) were independent risk factors for decompressive craniectomy. The risk of decompressive craniectomy increases to more than 30% with an ASPECT score<4, an NIHSS>16, and current antiplatelet use. ConclusionIn this multicenter registry, 9% of acute ischemic stroke patients (<60years old) treated with MT, required decompressive craniectomy. Higher NIHSS score, lower ASPECT score, and preadmission antiplatelet use increase the risk of subsequent requirement for decompressive craniectomy.

Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial

Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining intracranial pressure and brain tissue oxygen pressure (PbtO2) monitoring over a strategy of intracranial pressure monitoring only to reduce the proportion of patients with poor neurological outcome at 6 months. We did an open-label, randomised controlled superiority trial at 25 French tertiary referral centres. Within 16 h of brain injury, patients with severe traumatic brain injury (aged 18-75 years) were randomly assigned via a website to be managed during the first 5 days of admission to the intensive care unit either by intracranial pressure monitoring only or by both intracranial pressure and PbtO2 monitoring. Randomisation was stratified by age and centre. The study was open label due to the visibility of the intervention, but the statisticians and outcome assessors were masked to group allocation. The therapeutic objectives were to maintain intracranial pressure of 20 mm Hg or lower, and to keep PbtO2 (for those in the dual-monitoring group) above 20 mm Hg, at all times. The primary outcome was the proportion of patients with an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability) at 6 months after injury. The primary analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew consent or had protocol violations. This trial is registered with ClinicalTrials.gov, NCT02754063, and is completed. Between June 15, 2016, and April 17, 2021, 318 patients were randomly assigned to receive either intracranial pressure monitoring only (n=160) or both intracranial pressure and PbtO2 monitoring (n=158). 27 individuals with protocol violations were not included in the modified intention-to-treat analysis. Thus, the primary outcome was analysed for 144 patients in the intracranial pressure only group and 147 patients in the intracranial pressure and PbtO2 group. Compared with intracranial pressure monitoring only, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with GOSE score 1-4 (51% [95% CI 43-60] in the intracranial pressure monitoring only group vs 52% [43-60] in the intracranial pressure and PbtO2 monitoring group; odds ratio 1·0 [95% CI 0·6-1·7]; p=0·95). Two (1%) of 144 participants in the intracranial pressure only group and 12 (8%) of 147 participants in the intracranial pressure and PbtO2 group had catheter dysfunction (p=0.011). Six patients (4%) in the intracranial pressure and PbtO2 group had an intracrebral haematoma related to the catheter, compared with none in the intracranial pressure only group (p=0.030). No significant difference in deaths was found between the two groups at 12 months after injury. At 12 months, 33 deaths had occurred in the intracranial pressure group: 25 (76%) were attributable to the brain trauma, six (18%) were end-of-life decisions, and two (6%) due to sepsis. 34 deaths had occured in the intracranial pressure and PbtO2 group at 12 months: 25 (74%) were attributable to the brain trauma, six (18%) were end-of-life decisions, one (3%) due to pulmonary embolism, one (3%) due to haemorrhagic shock, and one (3%) due to cardiac arrest. After severe non-penetrating traumatic brain injury, intracranial pressure and PbtO2 monitoring did not reduce the proportion of patients with poor neurological outcome at 6 months. Technical failures related to intracerebral catheter and intracerebral haematoma were more frequent in the intracranial pressure and PbtO2 group. Further research is needed to assess whether a targeted approach to multimodal brain monitoring could be useful in subgroups of patients with severe traumatic brain injury-eg, those with high intracranial pressure on admission. The French National Program for Clinical Research, La Fondation des Gueules Cassées, and Integra Lifesciences.