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PERFUSE - A Real-World Study on Rheumatology Patients’ Persistence with Adalimumab Biosimilar SB5 in France: Impacts of Patient Experience
No full textInternational audienceAimThis study aimed to provide new insights into patient training and satisfaction using Patient-reported Outcome Measures (PROMs) and their impact on 12-month persistence using SB5 in France.BackgroundSB5 is an EMA-approved adalimumab biosimilar, demonstrating bioequivalence, equivalent efficacy, and similar safety and immunogenicity as the reference biologic.ObjectiveThe purpose of this study was to assess the effect of training practices on SB5 use in rheumatology and patient satisfaction, and measure their impact on 12-month persistence in real life in France.Methods507 eligible patients diagnosed with rheumatoid arthritis (n=116), psoriatic arthritis (n=78), or ankylosing spondylitis (n=313) who were enrolled in the observational PERFUSE study between October 2018 and December 2020 at 25 clinical sites across France were included in this analysis. PROMs were collected 1-month after baseline via an online questionnaire designed with patient associations’ input. Persistence of SB5 use was captured during routine visits. The study (clinical trial NCT03662919) first received regulatory approval from French authorities on March 21, 2018. The final amendment was approved on April 25th, 2019.ResultsTraining on the correct use of SB5 injections was accepted (naive = 92.4%; pre-treated = 82.6%) and appreciated (naive = 95.9%; pre-treated = 97.4%) by patients. Satisfaction scores were high for all subgroups. Higher satisfaction with the injection device was linked to a lower probability of discontinuing treatment (HR=0.87; 95% CI (0.79; 0.96); p<0.05), as was a worse perception of the illness assessed using the B-IPQ (HR=1.03; (1.00; 1.05); p<0.05). Moreover, a significantly higher proportion of ePRO (electronic Patient-reported Outcomes) respondents (n=221/507) remained on SB5 at 12 months than non-respondents (66.4% (59.3; 72.5) vs. 48.7% (42.4; 54.8); p<0.05).ConclusionLower initial satisfaction may serve as a useful indicator for identifying individuals at a higher risk of non-persistence. This could provide a basis for recommending the standardization of patient information practices throughout France, particularly for pre-treated patients
Syndactyly release with full-thickness skin graft harvested from the wrist: About 24 webspaces
No full textInternational audienceThe management of congenital syndactylies often requires the use of a full-thickness skin graft to reconstruct the affected web space. Traditionally, full-thickness skin grafts are harvested from the groin region, but using the anterior aspect of the wrist may offers benefits in terms of scar quality while simplifying surgical time. This descriptive study evaluates scar quality (at donor and recipient site) associated with full-thickness skin graft harvested from the volar wrist in syndactyly release. We conducted a retrospective single-center study including patients who underwent syndactyly release with full-thickness skin graft harvested from the anterior wrist. Scar assessment was performed using the Observer Scar Assesment Scale, the Vancouver Scar Scale and the Withey Score. Overall, our results show high scores for scars at both donor and recipient sites. In conclusion, harvesting full-thickness skin graft from the volar wrist in syndactyly release is a simple and effective option for covering defects on the digits, while producing high-quality scars
A specific metabolomic and lipidomic signature reveals the postpartum resolution of gestational diabetes mellitus or its evolution to type 2 diabetes in rat
No full textInternational audienceGestational diabetes mellitus (GDM) represents a major public health concern due to adverse maternal postpartum and long-term outcomes. Current strategies to manage GDM fail to reduce the maternal risk to develop later impaired glucose tolerance (IGT) and type 2 diabetes (T2D). In a rodent model of diet-induced GDM without obesity, we explored the perinatal metabolic adaptations in dams with gestational IGT followed by either persistent or resolved postpartum IGT. Female Sprague-Dawley rats were fed a high-fat high-sucrose (HFHS) or a chow [control group (CTL)] diet, 1 wk before mating and throughout gestation (G). Following parturition, HFHS dams were randomized to two subgroups: one switched to a chow diet and the other one maintained on an HFHS diet throughout lactation (L). Oral glucose tolerance tests (OGTTs) were performed, and plasma metabolome-lipidome were characterized at G12 and L12. We found that 1) in GDM-pregnant dams, IGT was associated with incomplete fatty acid oxidation (FAO), enhanced gluconeogenesis, altered insulin signaling, and oxidative stress; 2) improved glucose tolerance postpartum seemed to restore complete FAO along with elevation of nervonic acid-containing sphingomyelins, assumed to impart β-cell protection; and 3) persistence of IGT after delivery was associated with metabolites known to predict the early onset of insulin and leptin resistance, with maintained liver dysfunction. Our findings shed light on the impact of postpartum IGT evolution on maternal metabolic outcome after an episode of GDM. They suggest innovative strategies, implemented shortly after delivery and targeted on these biomarkers, should be explored to curb or delay the transition from GDM to T2D in these mothers.NEW & NOTEWORTHY Specific metabolomic/lipidomic features are associated with GDM postpartum outcomes. GDM-pregnant dams exhibit partial fatty acid oxidation and boosted gluconeogenesis. Resolution of postpartum IGT relies on nervonic acid-sphingomyelin, a β-cell protector. Postpartum IGT persistence suggests muscle insulin resistance and liver dysfunction
Lésions nécropsiques et stratégies préventives dans un cas de listériose bovine
No full textInternational audienceListeriosis, caused by Listeria monocytogenes , is less common in cattle than in small ruminants. It is a serious disease, mainly affecting cattle through the ingestion of contaminated silage. This intracellular bacterium crosses several physiological barriers and invades the central nervous system, causing meningoencephalitis characterised by unilateral neurological signs (facial hemiplegia, swallowing disorders). The article describes the case of a Prim’Holstein cow presenting these clinical signs and euthanised after her condition worsened. Necropsy revealed fibrinous meningitis and dry digestive contents. Histology revealed microabscesses in the brain stem, confirming listeriosis. Isolation of Listeria monocytogenes from culture supports this diagnosis. Treatment is based on early antibiotic therapy, but the prognosis is often guarded. Prevention involves rigorous control of silage quality and management of risk factors (stress, nutritional status). As listeriosis is a zoonosis, veterinary surgeons must be ever more vigilant in controlling it, as they are the guarantors of animal and human health.La listériose, causée par Listeria monocytogenes , est une maladie moins fréquente chez les bovins que chez les petits ruminants. C’est une maladie grave, touchant principalement les bovins via l’ingestion d’ensilage contaminé. Cette bactérie intracellulaire franchit plusieurs barrières physiologiques et envahit le système nerveux central, provoquant une méningo-encéphalite caractérisée par des signes neurologiques unilatéraux (hémiplégie faciale, troubles de la déglutition). L’article décrit le cas d’une vache Prim’Holstein présentant ces signes cliniques et euthanasiée après aggravation de son état. L’examen nécropsique révèle une méningite fibrineuse et un contenu digestif sec. L’histologie met en évidence des micro-abcès du tronc cérébral, confirmant la listériose. L’isolement de Listeria monocytogenes en culture vient appuyer ce diagnostic. Le traitement repose sur une antibiothérapie précoce, mais le pronostic est souvent réservé. La prévention passe par un contrôle rigoureux de la qualité de l’ensilage et la gestion des facteurs de risque (stress, état nutritionnel). La listériose étant une zoonose, sa maîtrise requiert une vigilance accrue des vétérinaires, garants de la santé animale et humaine
Evaluation de l'héritabilité de la sévérité et de l'évolution de la maladie valvulaire dégénérative mitrale à travers une étude échocardiographique des reproducteurs et de leur descendance chez le Cavalier King Charles Spaniel
No full textLa MVDM chez le CKCs est une affection majeure de cette race, avec une prévalence justifiant la mise en place de démarches visant à la réduire. Les objectifs de cette étude sont de comprendre, à travers les résultats de la campagne d’échocardiographie réalisée depuis 1999 par le club de race des CKCs, s'il existe un caractère héréditaire dans la sévérité et l’évolution de la MVDM, ainsi que d’explorer la pertinence d’un test échocardiographique à un stade précoce de la maladie (avant l’âge de 4 ans). Les résultats obtenus ont permis de souligner le rôle majeur de l’hérédité dans la sévérité de la MVDM. Cependant, cette étude n’a pas mis en évidence que l’évolution de la MVDM suivait une trajectoire différente en fonction de l’origine génétique des chiens. Ces résultats ont été observés aussi bien dans les tests tardifs que dans les tests précoces, où la maladie est moins exprimée, validant ainsi la pertinence de la réalisation de ce test dès les premières années de vie du chien. De plus, cette étude a permis de corroborer l’influence du sexe du chien sur la sévérité et la progression de la maladie, les mâles étant plus sensibles à celle-ci. Ainsi, la sélection des reproducteurs selon les critères établis dans le cadre de cette campagne s’avère essentielle pour réduire la prévalence des formes sévères de la MVDM dans les générations futures
Navitoclax acts synergistically with irradiation to induce apoptosis in preclinical models of H3K27M-altered diffuse midline glioma
No full textInternational audienceDiffuse midline gliomas (DMGs) with histone H3K27M mutations represent a devastating paediatric brain cancer characterised by abysmal prognosis and limited treatment options. The only approved treatment is radiotherapy (RT), but most of the tumours relapse with fatal consequences. The effects of RT remain unknown because patients are not biopsied during treatment. Here, we sought to investigate whether irradiation leads to senescence induction in DMG and explore the efficacy of senolytics. We show that ionising radiation induces senescence in various H3K27M-altered DMG cell lines. Senescence induction is demonstrated by immunocytochemistry, RNA-sequencing and analysis of SASP factors by ELISA. Through testing several senolytic compounds, we identify that Bcl2 family inhibitors (e.g., Navitoclax) act as potent senolytics, driving senescent DMG cells into apoptosis, primarily via Bcl-xL inhibition. Reinforcing these findings, proteolysis-targeting chimeras (PROTACs) targeting Bcl-xL and galacto-conjugated Navitoclax (Nav-Gal) also exhibit strong senolytic activity against senescent DMG cancer cells. Finally, we show that a combination of irradiation with Navitoclax enhances cancer cell apoptosis in an orthotopic xenograft DMG model. Together, the data demonstrate that ionising irradiation leads to senescence induction in H3K27M-altered human DMG cell lines, making them particularly sensitive to apoptosis through Bcl-xL inhibition
An easy and reproducible method for a large-zone deep partial-thickness burn model in the mini-pig
No full textInternational audienc
Productions Maraichères et climat - Multifonctionnalités et performances environnementales des réserves d'irrigation - Guide technique
No full textGuide technique issu du projet CLIMATVEGInternational audienceGuide technique issu du projet CLIMATVE
Optimisation de réseaux multi-énergies de distribution pour l'intégration de productions renouvelables
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Investigating microstructural features and tensile properties of 3D-printed co-polyester reinforced with carbon fibres
No full textInternational audienceThis study investigates the 3D printing of carbon fibre-reinforced copolyester (COP-CF) composites using fused filament fabrication (FFF) technology, with a focus on the influence of printing parameters on mechanical performance and microstructure. We explore the effects of different printing angles (0 • to 90 • ) on the tensile behaviour, pore connectivity, and microstructural characteristics of 3D-printed COP-CF specimens. Synchrotron X-ray microtomography is employed to analyse the internal structure of printed parts, revealing insights into porosity distribution and fibre alignment. Our results indicate that a 45 • printing angle yields the highest mechanical performance, with a tensile strength improvement approaching 70 MPa and a Young's modulus nearing 1 GPa, attributed to filament alignment in the loading direction and optimal load transfer. Additionally, the elongation at break reaches approximately 10 %, indicating a balance between strength and ductility. The study also highlights the role of process-induced porosity and its impact on mechanical properties. Additionally, the design and testing of a 3D-printed curved hook demonstrate the material's potential for functional applications under mixed-mode loading conditions effectively at a 45 • printing angle-outperforming other angles by a factor of 1.71. The findings underscore the importance of printing angle and microstructure control in optimizing the mechanical performance of 3D-printed COP-CF composites for technical applications.</div