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Laparoscopic Liver Resection in High-risk Anesthesia Patients A French Nationwide Study
No full textInternational audienceBackgroundStudies evaluating the impact of the American Society of Anesthesiologists Physical status (ASA-PS) score on outcomes after liver resection (LR) are currently lacking. The aim was to evaluate the value of ASA-PS score on perioperative outcomes for laparoscopic liver resection (LLR).MethodsThis is a retrospective analysis of patients who underwent LLR from 1996 to 2018 at 29 French medical centers. High-risk anesthesia patients were defined as those with ASA-PS scores ≥ 3. Postoperative outcomes including 90-day mortality, morbidity and failure to rescue (death within 90 days following any major postoperative complication) were compared between high- and low-risk anesthesia patients.ResultsOf 3154 patients included, 734 (23.3%) had ASA-PS scores ≥ 3. The 90-day mortality (2.6% vs. 0.6%), overall morbidity (42.0% vs. 33.8%), severe morbidity (11.2% vs. 7.4%) and failure to rescue (23.2% vs. 7.9%) rates were higher in the ASA-PS score ≥ 3 group (all p < 0.05). In the multivariable analysis, ASA-PS score ≥ 3 was an independent risk factor for failure to rescue after LLR in the study population.ConclusionsLLR in high-ASA patients can be performed with a higher rate of mortality and morbidity
Defiwaide : Pertinence de la waide dans le phytomanagement des sols pollués par les ETM ?
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The LiDAR Study and Web-based GIS of Zaldapa: A Contribution of the DANUBIUS Project to the International Archaeological Mission
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Patterns of relapse after postoperative radiotherapy in patients with oral cavity cancer and a flap
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Secondary Genetic Alterations and Measurable Residual Disease in Core Binding Factor Acute Myeloid Leukemia - a Study from the Acute Leukemia French Intergroup
No full textMeeting abstractInternational audienceContext. Measurable residual disease (MRD) is a major prognostic factor in Core Binding Factor (CBF) AML (Jourdan et al. 2014, Döhner et al., 2022). Recurrent genetic alterations like KIT or FLT3 gene mutations have also shown prognostic relevance but little is known about their prognostic value when accounting for MRD. Objective. We analyzed the prognostic value of recurrent genetic alterations when adjusted on early MRD response during the first line treatment of adult CBF-AML patients. Methods. We merged data from a retrospective multicenter study (NCT05070208) and the prospective CBF-2006 trial (NCT00428558) with similar fusion transcript MRD monitoring. Patients with CBFA (t(8;21)/RUNX1::RUNX1T1) or CBFB (inv(16)/CBFB::MYH11) AML in first CR/CRi after intensive chemotherapy were eligible if: 1) next-generation sequencing (NGS) was available at diagnosis; or 2) MRD was assessed at ≥ 1 timepoint during first line therapy. In patients with adequate samples, centralized NGS was performed using a CBF-AML specific panel of 62 genes. Primary endpoint was the risk for relapse including molecular relapse as defined by ELN (Döhner et al., 2022), with non-relapse mortality as a competing event. Variable selection was performed by a LASSO penalized cause-specific Cox model. Impact of genetic alterations on MRD kinetics was evaluated by clustering MRD by k-means. Discrimination was evaluated using time-dependent ROC-AUC for risk of relapse at 3 years. Results. 634 CBF-AML patients were included between 2007 and 2021 (311 females, 323 males; median age 45 years [range 18-80]), 295 (47%) with CBFA and 339 (53%) with CBFB AML. Induction regimens were based on 7+3 (72%), 9% and 2% patients receiving additional gemtuzumab ozogamicin or tyrosine kinase inhibitor, respectively. Consolidation courses were mainly intermediate/high dose cytarabine courses (93%) and only 5% patients were transplanted in first CR/CRi. In eligible CBFA AML patients (n=172), only KIT exon 17 mutation was selected using LASSO penalization. Exon 17 mutations (n=44 [26%]) significantly increased (csHR=2.27 [95%CI:1.38-3.74], p=0.001) but not other types of KIT mutations (n=19 [11%], csHR=1.23 [95%CI:0.57-2.63], p=0.60). Of note, KIT exon 17 mutations were not associated with a specific RUNX1::RUNX1T1 MRD trajectory. In eligible CBFB AML patients (n=190), FLT3 mutations were associated with a higher risk of relapse (csHR=1.03) whereas MYC mutations (csHR=0.96) or presence of any trisomy (csHR=0.99) had a favorable impact. Specifically, FLT3-ITD significantly increased risk of relapse (n=10 [5%], csHR=2.86 [95%CI:1.31-6.26], p=0.009) whereas the trend was non-significant for FLT3-TKD (n=32 [17%], csHR=1.62 [95%CI:0.94-2.77], p=0.08). MRD were clustered in 3 trajectories with rapid (36%), intermediate (30%), and slow responders (34%). Presence of any trisomy was associated with rapid responders (55% vs 28% without trisomy, p<0.0001) whereas FLT3 and MYC mutations were not associated with a specific MRD trajectory. Among early BM and PB MRD timepoints, post-induction BM MRD had the highest discrimination for CBFA AML (ROC-AUC: 0.633) and post-consolidation 1 PB MRD for CBFB AML (ROC-AUC: 0.628). In CBFA AML, post-induction BM MRD > 10-3 was a significant predictor of relapse (n=158/265, csHR=2.88 [95%CI:1.79-4.62], p<0.0001). In CBFB AML, post-consolidation 1 PB MRD > 10-5 was a strong predictor of relapse (n=80/195, csHR=2.64 [95%CI:1.66-4.21], p<0.0001). In CBFA AML multivariable analysis, KIT exon 17 mutations were associated with a higher risk of relapse (csHR=2.48 [95%CI:1.6-3.86], p=0.0001), independently of higher age (csHR=1.03 [95%CI:0.9-1.19], p=0.67), WBC (log10-scale, csHR=1.82 [95%CI:1.13-2.91], p=0.01), and post-induction BM MRD (csHR=2.49 [95%CI:1.53-4.07], p=0.0005). In CBFB AML, only post-consolidation 1 PB MRD was independently associated with risk of relapse (csHR=2.34 [95%CI:1.47-3.74], p=0.0009), when accounting for age (csHR=1.05 [95%CI:0.92-1.19], p=0.50), WBC (csHR=1.01 [95%CI:0.73-1.4], p=0.94),FLT3 mutation (csHR=1.51 [95%CI:0.98-2.3], p=0.06), MYC mutation (csHR=0.35 [95%CI:0.09-1.47], p=0.16) and trisomies (csHR=0.74 [95%CI:0.48-1.15], p=0.19). Conclusion. MRD remains the most important prognostic factor in patients with CBF-AML. Among recurrent genetic lesions, only KIT exon 17 mutations worsen prognosis independently of MRD in CBFA AML patients
EO2463 Peptide Immunotherapy in Patients with Newly Diagnosed Asymptomatic Follicular Lymphoma Results in Monotherapy Objective Clinical Responses Linked with Anti-Peptide Specific CD8 Memory T Cell Responses: The EONHL1-20/Sidney Study
No full textMeeting abstractInternational audienceBackground Follicular lymphoma (FL) is a generally indolent disease where a watch and wait strategy is standard in asymptomatic patients (pts) with a low tumor-burden. Harnessing antitumor immunity through an anti-tumor immunization strategy at this stage may delay or avoid the subsequent need for more toxic and complex therapies. EO2463 is a therapeutic vaccine designed from non-self protein sequences, derived from gut bacteria, including 4 HLA-A2 synthetically produced 9-mer CD8 cytotoxic T cell epitopes, exhibiting molecular mimicry with specific epitopes on the B cell markers CD20, CD22, CD37, and CD268 (BAFF-receptor). Additionally, EO2463 contains a CD4 helper epitope UCP2 derived from hTERT. The compound expands pre-existing memory CD8 T cells recognizing the non-self protein sequences from gut bacteria which can then cross-react with the selected B cell antigens on tumor cells. EO2463 is being used to drive anti-tumor immunity against B cell malignancies, and has demonstrated long-lasting, specific CD8-memory T cell responses and clinical activity in relapsed/refractory FL and marginal zone lymphoma (MZL) [J Clinical Oncol 2024, 42 (S16), 7058]. Furthermore, CD8 T cells expanded from samples of patients treated with EO2463 can kill HLA-A2 expressing lymphoblastoid cell lines presenting the B cell targets [Hematological Oncol 2023, 41 (S2), 581-582]. Methods The current report describes Cohort 2 of trial EONHL1-20/SIDNEY (NCT04669171) and includes pts with newly diagnosed, previously untreated FL, grade 1-3A, HLA-A2, and not in need of treatment. Pts receive EO2463 (300μg/peptide) SC with adjuvant Montanide ISA 51 VG, q2 weeks (w) x 4, then q4w, for a total of 12 doses (39w; PET-CTs at w6, w19, and w42). Planned accrual for this cohort is 25 pts. Immune responses were assayed on thawed pt peripheral blood mononuclear cells by flow cytometry and EO2463 peptide specific tetramers or by IFN-γ ELISPOT (assaying responses against 9-mer peptides from CD20, CD22, CD37, and CD268; and from peptides of EO2463) without any proceeding in vitro stimulation (ex vivo). Results As of June 2024, 15 pts had started study treatment. Median age was 62 (range 55-66) year, 7 male and 6 female, 2 pts Ann Arbor stage I/II, 5 stage III, and 8 stage IV. Ten of 15 pts were still on treatment; median treatment duration was 18.4 weeks (range 5-39 w) for all pts. Among 13 evaluable pts, best responses by PET-CT using Lugano criteria were 1 pt CR, 5 pts PR (46% objective responses (OR)), 3 pts SD, and 4 pts PD. Of those with PD per Lugano, 2 had isolated increases in FDG-uptake without increase in lesion size/number at w6 and both remain on treatment (per protocol based on LYRIC criteria). OR was first noted w6 in 3 pts and w19 in 3 pts; duration of response is not evaluable at this time due to short follow-up. The pt with CR had isolated increases in FDG-uptake at w6, PR at w19, and CR at w35. Anti-EO2463 immune responses were observed in 4 of 5 tested pts at the 1st testing timepoint (w5) and onwards (currently longest tested up until w31). In an exploratory analysis, the percentage of EO2463 peptide specific CD8 T cells measured by tetramers seemed linked to clinical response (OR 3 pts vs non-OR 2 pts; 2-sided T-test, p=0.02; range of percentages in pts with OR 0.85%-1.39% of all CD8 T cells in peripheral blood, range in pts with non-OR 0.17%-0.27%). Functionality and cross-reactivity of responses were shown by IFN-γ ELISPOT using 9-mer peptides corresponding to the B cell targets in 4 tested pts. Expanded antigen-specific CD8 T cells displayed a memory phenotype; effector/memory (TEM), and terminally differentiated effector memory CD8 T cells (TEMRA). The most common related AEs were grade 1 (7 pts) and grade 2 (5 pts) local administration site reactions (mainly erythema, pruritus, and induration). Other related AEs in > 1 pt were grade 1 headache (2 pts) and grade 1-3 fatigue/asthenia (3 pts). Asthenia lasting 2 days was the only related grade 3 adverse event (AE). Conclusions EO2463 monotherapy is associated with a very manageable safety profile and appears to demonstrate meaningful single-agent efficacy in FL. Consistent with the preclinical hypothesis, expansion of specific CD8 memory T cells may be associated with response. Results will be expanded at the meeting. Study EONHL1-20/SIDNEY also includes cohorts, not covered in this abstract, exploring EO2463 plus rituximab for 1st line FL/MZL, and EO2463 plus lenalidomide/rituximab in relapsed FL/MZL
A study of the degradation of indoor DSSCs after bufexamic acid treatment
No full textInternational audienceThe recent emergence of the Internet of Things paved the way for the development of smart items and self-powered devices. This new approach for domotics induced a need for efficiently powering these appliances under low light conditions, which gave rise to indoor photovoltaics. Among all the existing technologies available, 3rd generation photovoltaics proved to be highly efficient for this purpose. DSSCs showed to be particularly interesting [1] as they are an excellent compromise between efficiency and processability. In consequence, the industrial development of DSSCs is growing more and more, bringing a necessity for fabricating DSSCs stable for long periods of time.SL9 and SL10 are two recently published dyes [2] that have demonstrated high Power Conversion Efficiency (PCE) in co-sensitized devices in indoor and outdoor conditions. In this work, these dyes were synthetised and characterized using NMR, HRMS, UV-Vis spectroscopy and cyclic voltammetry. They were then integrated in industrially processed DSSCs to evaluate their long-term stability and performance under white LED light. As a result, co-adsorbed SL9 and SL10 displayed high PCE at 1000 lux of more than 25% after 3000 hours, making them comparable to benchmark sensitizers. Even at 130 lux of illumination, more than 22% PCE was recorded, exceeding most of other commercially available technologies.Literature has shown that the preliminary adsorption of bufexamic acid on the photoanode allows to improve the dense packing of the sensitizer grafted on the surface of the mesoporous film of titania [2, 3]. This method was applied to SL9/SL10 co-sensitized cells and contributed to increase the JSC and fill factor by a few percent, which is consistent with previous findings.Finally, a set of SL9/SL10 cells with and without pre-adsorption were subjected to accelerated stability tests to evaluate the influence of the acid pre-adsorption on the stability of the cells. The cells were then monitored under white LED light at low and moderate intensity for 1000 hours. After leading several tests, there was no clear evidence of a detrimental effect after bufexamic acid treatment. Indeed, both typologies of cells demonstrated similar trends for the decrease of the VOC and JSC. We assume that while the density of the dye monolayer does have a positive effect on the quantity of light absorbed and converted, there is no evident related mechanism influencing the degradation of the cells overtime. This makes bufexamic acid pre-adsorption an excellent option for improving the cell efficiency without compromising the stability in the long run
Dielectric properties of SrTiO 3 /PbTiO 3 /SrTiO 3 epitaxial structures
No full textInternational audienceThe dielectric properties of layered two-component structures consisting of a dielectric of strontium titanate SrTiO3 and a ferroelectric of lead titanate PbTiO3 are investigated. In these structures, a ferroelectric phase transition occurs at a temperature of 544 ˚С, which significantly exceeds the phase transition temperature of ferroelectric PbTiO3. This effect may be due to the very small thickness of the PbTiO3 ferroelectric layer and the influence of the dielectric SrTiO3
Épidémiologie et caractéristiques des uvéites en Picardie sur 10 ans
No full textInternational audiencePurpose: To describe the demographic and clinical characteristics, etiology and management of patients presenting with uveitis to a secondary center.Materials and methods: This was a retrospective, single-center study including patients over 18 years of age who were diagnosed with uveitis and followed between January 2013 and January 2023.Results: In all, 1082 patients, 537 men (49.7%) and 545 women (50.3%), were included. The mean age at the first visit was 48.2±18.6 years. The most frequent anatomical location was anterior uveitis (784 cases, 72.5%), followed by panuveitis (133 cases, 12.3%). Posterior uveitis (103 cases, 9.5%) and intermediate uveitis (62 cases, 5.7%) were less common. An etiology was identified in 65.3% of anterior uveitis, 73.8% of posterior uveitis, and 64.7% of panuveitis. In contrast, only 38.7% of intermediate uveitis cases had an identified etiology. The most frequent causes of uveitis were herpes group virus-related uveitis, HLA B-27 related uveitis, sarcoidosis, and toxoplasmosis. Among patients with non-infectious uveitis, 111 (10.3%) were treated with systemic corticosteroids, 93 (8.5%) with antimetabolites as a steroid-sparing approach, and 67 (6.2%) received biologic therapy.Conclusion: These results summarize the sociodemographic and clinical characteristics of patients with uveitis in northern France. There are distinct similarities and differences in the patterns of uveitis presentation, varying significantly according to geographical and environmental factors, which may help physicians in this region to manage uveitis.ObjectifDécrire les caractéristiques démographiques, cliniques, les étiologies retrouvées et la prise en charge des patients ayant consulté pour une uvéite dans un centre secondaire.Matériel et méthodesIl s’agit d’une étude rétrospective incluant les patients de plus de 18 ans ayant été pris en charge pour une uvéite entre janvier 2013 et janvier 2023 dans un hôpital universitaire de Picardie. Les données démographiques, caractéristiques cliniques, les étiologies et les traitements ont été recueillis.RésultatsAu total, 1082 patients ont été inclus, répartis en 537 hommes (49,7 %) et 545 femmes (50,3 %). L’âge moyen à la première consultation était de 48,2 ans ± 18,6 ans. La localisation anatomique la plus fréquente était l’uvéite antérieure avec 784 cas (72,5 %), suivie de la panuvéite avec 133 cas (12,3 %). L’uvéite postérieure et l’uvéite intermédiaire étaient moins fréquentes avec respectivement 103 cas (9,5 %) et 62 cas (5,7 %). Une étiologie a été retrouvée dans 65,3 % des uvéites antérieures, 73,8 % des uvéites postérieures et 64,7 % des panuvéites, tandis que seules 38,7 % des uvéites intermédiaires ont abouti à une étiologie. Les causes d’uvéites les plus fréquentes étaient les uvéites liées aux virus du groupe herpès, les uvéites liées à HLA B-27, la sarcoïdose et la toxoplasmose. Parmi les patients présentant une uvéite non infectieuse, 111 (10,3 %) ont bénéficié de corticoïdes par voie systémique, 93 (8,5 %) ont été traités par des immunosuppresseurs, et 67 (6,2 %) ont reçu des biothérapies.ConclusionCes résultats reflètent avec précision les caractéristiques sociodémographiques et cliniques des patients atteints d’uvéite dans le nord de la France. Les schémas de présentation des uvéites montrent des similitudes et des différences distinctes selon des facteurs géographiques et environnementaux
Semi-Quantic thermo-optical modelling of the Ultra-Short Pulsed Laser ablation process on grain-oriented electrical steels
No full textInternational audienceIn the context of loss and vibrations reduction in electrical steel using refinement techniques of various domains, a new process called Ultra-Short Pulsed Laser ablation process (USPL ablation) has been recently proposed. This paper contributes to the modelling and understanding of laser-matter interactions using Ultra-Short Pulses with the aim to optimise the impact of the ablation process onto the performances of soft ferromagnetic materials. The paper includes a description, model and calculation of a transient, non linear and thermo-optical physic with quantum origin, for which the steel is considered as an atoms’ lattice embedded in a free electrons’ gas. The model assumes a significant separation between the thermal diffusion time of electrons and that of the atoms in the crystal lattice, but with a coupling between the electrons and the phonons, amplified by a plasma generation at the high temperature of the electrons’ gas. This strong coupling leads to an energy transfer from the electrons’ gas towards the crystal’s phonons with a favourable transient condition on the lattice temperature above the ablation threshold by sublimation. Of all the possible solutions, only an average and analytical two-temperatures model makes it possible to converge and obtain all the useful solutions in a reasonable time that is compatible with some optimisation methods. This manuscript provides its analytical solution considering either 1 or N pulses with high repetition frequencies, which has not been available up to now in the literature. However, the Finite Element Method (FEM) remains the most accurate when considering the heating curves obtained by the model