Volume instabilities in capillary flow of pure SBR and SBR compounds

International audienceThe flow instabilities of pure styrene-butadiene-rubber (SBR) and SBR compounds filled with silica were characterized using capillary rheometry. Above a critical shear stress, volume defects develop, leading to products of unacceptable quality. Unlike other polymers (polystyrene and low density polyethylene), the onset of these defects is concomitant with a transition from no slip (or weak slip) to strong slip conditions. Volume instabilities are affected by the silica content and the type of additive (coating or coupling agents) present in the compounds. A method based on image analysis is proposed to quantify volume defects, which can help to compare the different compounds in terms of extrusion quality

Antibiorésistance : outils pour une recherche translationnelle efficace

La crise qui résulte de la montée des résistances bactériennes menace la santé humaine, animale et environnementale. L’impact sanitaire et économique de la crise est massif. Alors que l’alerte est largement donnée et que des mécanismes et des programmes d’aide à l’innovation pour lutter contre l’antibiorésistance ont été mis en place, force est de constater que les nouveaux produits antibiotiques proposés n’arrivent pas à trouver une rentabilité économique leur permettant d’atteindre le marché et d’être au service des patients et de la communauté. Par ailleurs, il est nécessaire de développer des outils/indicateurs pour définir les interventions probantes en matière de lutte contre l’antibiorésistance. Les travaux de réflexion relatés dans cet article sont concentrés sur ces deux aspects de la recherche translationnelle : – la prévention et l’impact en santé de la problématique antibiorésistance, et – les spécificités de la recherche clinique pour innover en matière de lutte contre l’antibiorésistance. Cet article, issu des réflexions d’un groupe d’experts français, propose des solutions directement opérationnelles qui pourraient être mises en place rapidement et transformer radicalement la qualité et la quantité de nos moyens de lutte

Antibiotic resistance: Tools for effective translational research

The rising emergence of bacterial resistances has led to a crisis which threatens human, animal and environmental health. The impact of the emergency is enormous in terms of public health and economics. Although there is a global awareness of the warnings and programmes supporting innovative actions to combat fight against antibiotic resistance, it must be admitted that proposed new antibiotics fail to find the economic profitability necessary for them to reach the market and become available for patients and the community. Moreover, it is necessary to develop tools/indicators to define effective interventions against antibiotic resistance. The work of the think-tank reported in this article concentrated on two aspects of translational research: - prevention and the impact on health of the antibiotic resistance issue, and - the specific requirements of clinical research leading to innovation in the fight against antibiotic resistance. This article, which reflects the thoughts of a group of French experts, proposes directly operational solutions which could be rapidly implemented and radically transform the quality and quantity of our resources available for the combat

Atgam Efficacy and Safety in Moderate-to-Very Severe Acquired Aplastic Anemia: Outcome of a Large Multicenter Cohort of 634 Children and Adults from the French Authorization for Temporary Use Surveillance Program

International audienceIntroduction Acquired aplastic anemia (AA) is a rare immunological disease leading to bone marrow failure. First-line treatment in patients aged >40 years or without a matched related donor is immunosuppressive therapy (IST) based on anti-human T lymphocyte immunoglobulin (ATG) plus cyclosporine. This ATGAM Temporary Use Authorization program was a retrospective, multicenter study to report safety and efficacy surveillance data on ATGAM use in patients with AA. Methods This study collected surveillance data from the ATGAM Named Patients Program for French authorities ahead of ATGAM registration. Patients were treated with ATGAM 40 mg/kg for 4 days in addition to cyclosporine. Safety and efficacy data were collected from patients treated from September 2011 to August 2022 and reported to the French authority every 6 months. Patients were classified as severe AA if they had 2 of the following criteria: neutrophil count <0.5x10 9/L, platelet count <20x10 9/L, or reticulocyte count <60x10 9/L. Very severe AA: same as severe except neutrophil count <0.2x10 9/L. Patients not meeting criteria for very severe/severe AA were classified as moderate. Patient response was evaluated using the RACE study criteria (Peffault de Latour, et al [2022]), for severe AA: complete response was defined as: hemoglobin >100g/L, neutrophil count >1.0x10 9/L, and platelet count >100x10 9/L; partial response: no longer meeting criteria for severe disease; no response: still severe AA and/or transfusion dependent. For moderate AA (Marsh, et al [1999]), complete response was defined as: neutrophil count >2.0x10 9/L and platelet count >100x10 9/L; partial response: neutrophil count >1.0x10 9/L and platelet count >30x10 9/L; no response: transfusion dependent. Patients were classified as receiving first-line treatment (never received ATG), refractory (failed to respond to previous IST with ATG within 12 months before initial ATGAM), or relapse (recurrence of AA after a positive response to IST with ATG), regardless of AA severity. Results In total, 634 patients with moderate-to-very severe AA were treated with ATGAM (n=537 first-line; n=68 refractory/relapse; n=29 not classified) in addition to cyclosporine (40 first-line patients also received eltrombopag) from January 2012 to August 2022. By severity, n=124 were moderate, n=317 severe, n=133 very severe, and n=60 severity unknown. Patient demographics are shown in Table 1. Overall response (partial+complete) in patients on first-line therapy at 3, 6, and 12 months was 22.5% (n=78), 50.6% (n=156), and 79.2% (n=164), respectively. By severity, overall response rates in first-line therapy for moderate and severe/very severe cohorts, respectively, were: 25.0% (n=20) and 21.7% (n=58) at 3 months; 56.8% (n=42) and 48.7% (n=114) at 6 months; and 74.1% (n=40) and 81.0% (n=124) at 12 months. Overall response at 6 and 12 months by age and AA severity in patients on first-line treatment is shown in Table 2. Median duration of follow-up was 12.4 months. Overall survival (95% confidence interval) at 12 months for all patients was 91.5% (88.8-93.6). The treatment was well tolerated, and no new safety signals were observed with ATGAM. Cumulatively, 1,087 adverse events were reported in 364 patients over the entire program period, the majority of which were disease related. Conclusion This real-world, retrospective study utilizing surveillance data showed response rates in line with the recent RACE study (Peffault de Latour, et al [2022]) for patients with first-line severe AA treated with a combination of ATGAM and cyclosporine. No new safety risks were identified in this large cohort of patients. Treatment with ATGAM remains of benefit in patients with moderate-to-very severe AA

P776: ATGAM EFFICACY AND SAFETY IN MODERATE AND SEVERE ACQUIRED APLASTIC ANEMIA: OUTCOME OF A LARGE MULTICENTER COHORT OF 634 CHILDREN AND ADULTS FROM THE FRENCH AUTHORIZATION FOR TEMPORARY USE SURVEILLANCE PROGRAM

International audienceBackground: Acquired aplastic anemia (AA) is a rare immunological disease resulting in bone marrow failure. Patients can be treated either by immunosuppressive therapy (IST) or by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT is the recommended treatment in patients younger than 40 years old with an available matched-related donor. IST is the recommended option for other patients: from the randomized trial published by Scheinberg in 2011, ATGAM® (horse anti-human T lymphocyte immunoglobulin) in addition to cyclosporine was the reference first-line IST for moderate to severe AA.Aims: This retrospective, multicentric study was conducted to report safety and efficacy data from ATGAM use in patients with AA utilizing surveillance data.Methods: This Temporary Use Authorization (ATU) program was initiated to collect surveillance data from the ATGAM Named Patients Program for French authorities before ATGAM was registered. This is the final report from this program. Safety and efficacy data was collected from the program and reported every 6 months. ATGAM was dosed at 40 mg/kg for 4 days in all patients that received treatment. Severity of AA was classified according to Camitta and EBMT scores. Response criteria followed the British Committee for Standards in Haematology Guidelines. For severe AA, no response: still severe; partial response: transfusion independence and the patient no longer met criteria for severe disease; complete response: hemoglobin was normal, neutrophil count >1.5x109/L, and platelet count >150x109/L. For moderate AA: no response: worse or did not meet criteria for response that included transfusion independence (if previously dependent) or doubling or normalization of at least 1 cell line or an increase of baseline hemoglobin, or an increase of baseline neutrophils or increase of baseline; complete response: the same criteria as for severe AA.Results: 634 patients (including 148 children) with moderate to very severe AA received ATGAM (n=537 first line; n=68 refractory/relapse; n=29 not classified) in addition to cyclosporine from January 2012 to August 2022. Overall hematologic response (Complete + Partial) at 6 months was 62.3% in the combined population. By severity, response rates were 84.4%, 50.8%, and 36.4% among patients with moderate, severe, and very severe AA, respectively, receiving first-line therapy (n=537; Table). By age, response rates were respectively 54.3%, 65.2%, and 64.4% in children (≤17 years), adults (≥18-<65 years), and elderly (≥65 years) patients. The overall survival rate (95% confidence interval) at 3 years was 96.9% (91.9-98.8%) in children, 83.4% (77.1-88.1%) in adults, and 79.7% (65.9-88.3%) in elderly patients. Treatment was well tolerated for the majority of patients. In total, 1087 adverse events (485 serious adverse events) were reported, with 48 fatal events.Summary/Conclusion: Reported response rate and overall survival in this real-life surveillance study are in line with a 2011 randomized controlled study comparing horse versus rabbit ATG (Scheinberg, et al [2011]) and control group of the most recent study RACE (Peffault de Latour, et al [2022]). The relatively large number of patients in this study compared with other similar studies in patients with AA adds to the robustness of this real-world data study. No new safety risks were identified, and this study showed that use of ATGAM remains favorable in this patient population