001 Predictive Value of Post Treatment Platelet Reactivity for Occurrence of Post-discharge Bleeding After Non ST Elevation Acute Coronary Syndrome

AimsWe assessed prospectively the association between occurrence of post-discharge non–CABG-related TIMI major and minor bleedings and post treatment platelet reactivity in patients with Non ST Elevation Acute Coronary Syndrome (NSTE ACS).Methods and Results597 consecutive patients admitted with NSTE ACS were prospectively included. Between hospital discharge and one month follow-up, we observed 16 (2.7%) non–CABG-related TIMI hemorrhagic complications including 5 (0.84%) major and 11 (1.8%) minor bleeds. Patients with bleeding had significantly lower post treatment values of ADP-induced aggregation (43±14% versus. 56±19%, P=0.002) and platelet reactivity index VASP (43±14% versus 54±23%; P=0.04) and a trend for lower values of arachidonic acid-induced aggregation (2.4±5.4 versus 13±21; P=0.27). After stratification by quartiles based on post treatment ADP-induced platelet aggregation, we identified patients in the first quartile as hyper-responders with very low post treatment platelet reactivity, below <40%. The risk of TIMI major and minor bleeding was significantly higher in the first quartile of hyper-responders than in the others quartiles: 10 (6.6%) versus 6 (1.4%), p=0.001.ConclusionOur results suggest that assessment of post treatment platelet reactivity might be used to detect hyper responders to antiplatelet therapy with higher risk of non-CABG related bleedings and tailor antiplatelet therapy according to both ischemic and bleeding risk

073: Very long-term effects of pacing therapy in Hypertrophic Obstructive Cardiomyopathy (HOCM)

The clinical value of DDD pacing as primary treatment of HOCM remains controversial. Very long-term data are lacking.Aimssingle-centre observational study aimed at describing the very long term effects on symptoms, clinical and echocardiographic outcomesPatients54 patients (59±14 years) with symptomatic (NYHA Class >2) drug-refractory HOCM implanted with a DDD pacemaker with or without defibrillator between 1991 and 2007 and followed up to 20 years (mean 11.5; range 0,4-21,8).Main resultsare summarised in table. No patient had myomectomy or septal ablation during follow-up (f/u). NYHA functional class and other symptoms were significantly improved at 1-2 years and at the end of f/u. Left ventricular outflow tract (LVOT) gradient decreased by a mean of 78% at 1-2 years and 89% at end f/u consistent with SAM resolution. LV ejection fraction decreased over time with a mean value of 56% at end f/u without evidence of cavity dilatation. The actuarial survival rate was 90% at 5-yrs and 65% at 10-yrs. 24 patients died, 19 from non cardiac cause and 5 cardiovascular. 2 patients had heart transplant after 8 and 13yrs.ConclusionThe clinical and echocardiographic outcome of HOCM patients treated by DDD pacing seems favourable, inviting to re-evaluate the exact value of the therapy in further controlled studiesTable – Main results.Baseline3 months1-2 yearsEnd f/uP valueNYHA functional class, (%)<0,0001Grade 10313536Grade 243535957Grade 3521667Grade 45000Syncope/nearsyncope (%)76/482/22/22/2<0,0001Angina (%)57444<0,0001LVOT gradient (mmHg)79±3620±2411±158±21<0,0001SAM (%)96383016<0,0001LVEF (%)63,5±7,561±759±756±90,05LVEDD (%)47±5NANA43±120,3

A kinematic-geometric model based on ankles’ depth trajectory in frontal plane for gait analysis using a single RGB-D camera

International audienceThe emergence of RGB-D cameras and the development of pose estimation algorithms offer opportunities in biomechanics. However, some challenges still remain when using them for gait analysis, including noise which leads to misidentification of gait events and inaccuracy.Therefore, we present a novel kinematic-geometric model for spatio-temporal gait analysis, based on ankles’ trajectory in the frontal plane and distance-to-camera data (depth). Our approach consists of three main steps: identification of the gait pattern and modeling via parameterized curves, development of a fitting algorithm, and computation of locomotive indices. The proposed fitting algorithm applies on both ankles’ depth data simultaneously, by minimizing through numerical optimization some geometric and biomechanical error functions. For validation, 15 subjects were asked to walk inside the walkway of the OptoGait, while the OptoGait and an RGB-D camera (Microsoft Azure Kinect) were both recording. Then, the spatiotemporal parameters of both feet were computed using the OptoGait and the proposed model. Validation results show that the proposed model yields good to excellent absolute statistical agreement (0.86≤Rc≤ 0.99). Our kinematic-geometric model offers several benefits: (1) It relies only on the ankles’ depth trajectory both for gait events extraction and spatio-temporal parameters’ calculation; (2) it is usablewith any kind of RGB-D camera or even with 3D marker-based motion analysis systems in absence of toes’ and heels’ markers; and (3) it enables improving the results by denoising and smoothing the ankles’ depth trajectory. Hence, the proposed kinematic-geometric model facilitates the development of portable markerless systems for accurate gait analysis

GREAT — a randomized aneurysm trial. Design of a randomized controlled multicenter study comparing HydroSoft/HydroFrame and bare platinum coils for endovascular aneurysm treatment

International audienceThe effectiveness of a hybrid hydrogel platinum detachable coil (HydroCoil; MicroVention Inc., Tustin, CA) for endovascular aneurysm treatment has been proven in a recently published RCT. Due to technical restrictions (coil stiffness, time restriction for placement), the HydroSoft coil as well as a corresponding 3D framing coil, the HydroFrame coil (MicroVention Inc., Tustin, CA), a class of new softer coils containing less hydrogel and swelling more slowly than the HydroCoil, have been developed and brought to clinical practice. The present study aims to compare the effectiveness of endovascular aneurysm treatment with coil embolization between patients allocated HydroSoft/HydroFrame versus bare platinum coiling. GREAT is a randomized, controlled, multicentre trial in patients bearing cerebral aneurysms to be treated by coil embolization. Eligible patients were randomized to either coil embolization with HydroSoft/HydroFrame coils (>50 % of administered coil length), or bare platinum coils. Inclusion criteria were as follows: age 18-75, ruptured aneurysm (WFNS 1-3) and unruptured aneurysm with a diameter between 4 and 12 mm. Anatomy such that endovascular coil occlusion deemed possible and willingness of the neurointerventionalist to use either HydroSoft/HydroFrame or bare platinum coils. Exclusion criteria were as follows: aneurysms previously treated by coiling or clipping. Primary endpoint is a composite of major aneurysm recurrence on follow-up angiography and poor clinical outcome (modified Rankin scale 3 or higher), both assessed at 18 months post treatment. Risk differences for poor outcomes will be estimated in a modified intention-to-treat analysis stratified by rupture status (DRKS-ID: DRKS00003132)

More rapid blood interferon α2 decline in fatal versus surviving COVID-19 patients

BackgroundThe clinical outcome of COVID-19 pneumonia is highly variable. Few biological predictive factors have been identified. Genetic and immunological studies suggest that type 1 interferons (IFN) are essential to control SARS-CoV-2 infection.ObjectiveTo study the link between change in blood IFN-α2 level and plasma SARS-Cov2 viral load over time and subsequent death in patients with severe and critical COVID-19.MethodsOne hundred and forty patients from the CORIMUNO-19 cohort hospitalized with severe or critical COVID-19 pneumonia, all requiring oxygen or ventilation, were prospectively studied. Blood IFN-α2 was evaluated using the Single Molecule Array technology. Anti-IFN-α2 auto-Abs were determined with a reporter luciferase activity. Plasma SARS-Cov2 viral load was measured using droplet digital PCR targeting the Nucleocapsid gene of the SARS-CoV-2 positive-strand RNA genome.ResultsAlthough the percentage of plasmacytoid dendritic cells was low, the blood IFN-α2 level was higher in patients than in healthy controls and was correlated to SARS-CoV-2 plasma viral load at entry. Neutralizing anti-IFN-α2 auto-antibodies were detected in 5% of patients, associated with a lower baseline level of blood IFN-α2. A longitudinal analysis found that a more rapid decline of blood IFN-α2 was observed in fatal versus surviving patients: mortality HR=3.15 (95% CI 1.14–8.66) in rapid versus slow decliners. Likewise, a high level of plasma SARS-CoV-2 RNA was associated with death risk in patients with severe COVID-19.ConclusionThese findings could suggest an interest in evaluating type 1 IFN treatment in patients with severe COVID-19 and type 1 IFN decline, eventually combined with anti-inflammatory drugs.Clinical trial registrationhttps://clinicaltrials.gov, identifiers NCT04324073, NCT04331808, NCT04341584

A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors

Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient's tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies

Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction

Background: Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). Objectives: This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. Methods: Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. Results: Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. Conclusions: In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden.</p

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer : An International Multicenter Cohort Study

Background. Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS.Methods. This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression.Results. The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS.Conclusions. This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.Peer reviewe