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Abstract Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets ( 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.

Abstract Personality is a central concept and a cross-domain explanatory factor in psychology to characterize and differentiate individuals. Surprisingly, among the many studies on oculomotor behavior, only a few have investigated how personality influences the exploration of a visual stimulus. Due to the limited number of existing studies, it is still uncertain if markers of personality in eye movements are always observable in eye movements across various exploration contexts. Here, introducing a novel concept of gaze-based signatures of personality, we used visual exploration metrics to detect personality signatures across various exploration contexts (visual search and free-viewing on images and webpages) in 91 participants. Personality data were collected as in the reference paper that validated the French version of the Big Five Inventory. Linear regression analyses demonstrated that while Extraversion and Openness to Experience did not correlate with any particular exploration metric, the other three traits–Conscientiousness, Agreeableness, and Neuroticism–correlated robustly with all exploration metrics in different visual exploration contexts. Our study provides evidence for the capture of the gaze-based signature of personality from very brief eye movement recordings.

In geosciences, multi-model ensembles are helpful to explore the robustness of a range of results. To obtain a synthetic and improved representation of the studied dynamic system, the models are usually weighted. The simplest method, namely the model democracy, gives equal weights to all models, while more advanced approaches base weights on agreement with available observations. Here, we focus on determining weights for various versions of an idealized model of the Atlantic Meridional Overturning Circulation. This is done by assessing their performance against synthetic observations (generated from one of the model versions) within a data assimilation framework using the ensemble Kalman filter (EnKF). In contrast to traditional data assimilation, we implement data-driven forecasts using the analog method based on catalogs of short-term trajectories. This approach allows us to efficiently emulate the model's dynamics while keeping computational costs low. For each model version, we compute a local performance metric, known as the contextual model evidence, to compare observations and model forecasts. This metric, based on the innovation likelihood, is sensitive to differences in model dynamics and considers forecast and observation uncertainties. Finally, the weights are calculated using both model performance and model co-dependency and then evaluated on averages of long-term simulations. Results show good performance in identifying numerical simulations that best replicate observed short-term variations. Additionally, it outperforms benchmark approaches such as strategies based on model democracy or climatology when reconstructing missing distributions. These findings encourage the application of the proposed methodology to more complex datasets in the future, like climate simulations.

Abstract Aims Predicting mortality in severe AL cardiac amyloidosis is challenging due to elevated biomarker levels and limited thresholds for stratifying severe cardiac damage. Methods and results This prospective, observational, cohort study included de novo, confirmed cardiac AL amyloidosis patients at the Henri Mondor National Reference Centre. The goal was to identify predictors of mortality to enhance prognostic stratification and improve informed decision‐making regarding therapy. Over the 12‐year study period, among the 233 patients included, 133 were NYHA III‐IV and 179 Mayo 2004 III. The independent predictors for mortality identified were hsTnT, NT‐proBNP, cardiac output, and conjugated bilirubin. A novel prognostic, conditional stratification, Mondor amyloidosis cardiac staging (MACS) was developed with biomarker cut‐off values for Stage 1: hsTnT ≤ 107 ng/L and NT‐proBNP ≤ 3867 ng/L (n = 77; 33%); for stage 2 NT‐proBNP > 3867 ng/L (n = 72; 30%). For stage 3, if troponin >107 ng/L, regardless of NT‐proBNP then CB 4 μmol/L, was added (n = 41; 17.5%) and stage 4: CB > 4 μmol/L (n = 43; 18.5%). The median overall survival was 8 months 95% CI [2–24]. At 1 year, 102 (44%) patients died and the Kaplan–Meier median survival with MACS Stage 1 was not reached, while stage 2 was 15.2 months (95% CI [11–18]) and stage 3, 6.6 months (95% CI [1–13]). Notably, among European stage II patients, 17.1%, n = 8 were MACS stage 3 and European stage IIIb 21.4% (n = 23) were MACS stage 4. Importantly, among European stage IIIb patients 42.2% (n = 29) were classified MACS stage 4 and 12.5% n = 9 were only MACS stage 2. Conclusions The Mondor prognostic staging system, including conjugate bilirubin may significantly improve prognostic stratification for patients with severe cardiac amyloidosis.

Objectives: Daratumumab-treated myeloma patients may face increased seasonal influenza risk due to weakened postvaccination immune responses, especially with daratumumab treatment. We aimed to assess humoral responses to boosted influenza vaccination in daratumumab-treated or -untreated patients. Methods: In a single-center study, we evaluated humoral responses (hemagglutination-inhibition assay) one month following a two-injection (4-weeks apart) influenza vaccination (standard dose) in 84 patients with multiple myeloma (40 with daratumumab in the past year). Results: Seroprotection rates (titer ≥1/40) after the second vaccine injection were low across vaccinal subtypes (except for A-H3N2): 71.3% (A-H3N2), 19.7% (A-H1N1pdm09), 9.9% (B-Victoria), 11.3% (B-Yamagata). Only A-H3N2 seroprotection rates significantly increased with the booster in daratumumab-treated patients (30% (12/40) after one injection vs 55% (22/40) after the boost; P = 0.01).After propensity score weighting, daratumumab was not significantly associated with a reduced likelihood of seroprotection against at least one vaccine strain (OR 0.65 [95% CI: 0.22-1.88]). Conclusion: While daratumumab treatment did not lead to a significant reduction in seroprotection rates following influenza vaccination, a booster vaccine injection demonstrated potential benefit for specific strains (A-H3N2) in patients undergoing daratumumab treatment. Nevertheless, the overall low response rates in patients with multiple myeloma necessitates the development of alternative vaccination and prophylaxis strategies.

Laser pulses were applied to a target mounted on a ballistic pendulum to study the momentum imparted by a laser shock impact. Photonic Doppler Velocimetry was used to assess the momentum imparted by each laser pulse. To increase the momentum produced, a layer of polymer transparent to the laser wavelength was applied to the surface of the targets to confine the plasma generated as a result of the laser–matter interaction. This yielded momentum coupling coefficients one hundred times higher than those obtained for equivalent laser parameters in the classical direct regime configuration. The study was completed by simulating the experiments with the one-dimensional Lagrangian hydrodynamics code ESTHER, which showed good agreement with the experimental results. [ABSTRACT FROM AUTHOR]

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