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Transcatheter Edge-to-Edge Repair in Patients With Primary Tricuspid Regurgitation
No full textInternational audienceBackground: Tricuspid regurgitation (TR) leads to right heart congestion and increased mortality risk. Unlike secondary TR, primary TR results from leaflet degeneration. Transcatheter edge-to-edge repair (TEER) is widely used for TR. However, its feasibility primary TR remains uncertain.Objectives: The aim of this study was to assess the safety and feasibility of TEER in patients with primary TR.Methods: The primary TR registry is a multicenter cohort study of patients with primary TR undergoing TEER. Echocardiographic assessment classified leaflet pathology into type 1 (flail), type 2 (billowing prolapse), type 3 (perforation), and type 4 (restricted mobility). The primary endpoint was TR reduction to moderate or less at discharge.Results: From December 2016 to April 2023, 114 patients (mean age 79.9 years, 53.5% men) were included. Most patients were in NYHA functional class III or IV (83.3%), with a median TRI-SCORE of 5.0. The TR pathologies were type 1 (28.1%), type 2 (61.4%), and type 4 (10.5%), with no type 3 cases. Device deployment was achieved in 95.6%, and 83.3% showed TR reduction to moderate or less. In-hospital mortality was 1.8%, and single-leaflet device attachment occurred in 3.5%. At 1 year, 79.7% of patients had TR moderate or less, with significant reductions in vena contracta (-5.0 mm; P < 0.001), annular diameter (-2.0 mm; P = 0.003), and mid right ventricular diameter (-3.0 mm; P < 0.001). NYHA functional class also improved significantly (NYHA functional class I or II: 17.1% at baseline vs 66.5% at follow-up; P < 0.001).Conclusions: TEER is a safe and effective option for primary TR, promoting right heart reverse remodeling and symptomatic relief, offering a vital alternative to surgery in selected patients
Adaptation strategies to manage summer forage shortages improve animal performance and better maintain milk and cheese quality in grass- versus corn-based dairy systems
No full textInternational audienceIn semi-mountainous grass-based dairy systems, summer droughts frequently reduce grass availability, with implications for animal performance as well as milk and cheese quality. The objective of our study was to investigate the effect of a simulated summer forage shortage in a traditional semi-mountainous grass-based system versus a corn-based system with part-time grazing. During a 19-wk experiment, 26 Prim'Holstein and 14 Montb & eacute;liarde cows were blocked in 4 balanced groups of 10 cows. During the first 8 wk, 2 groups were fed a grass-based diet (75% of grazed grass, 25% of hay and concentrates) and the remainder were fed a corn-based diet (75% mixed ration, 25% of grazed grass). During the following 11 wk, one group in each feeding system was subjected to a reduction in grazed grass intake and a corresponding increase in indoor feeding, resulting in 50% of grazed grass for grass-fed cows and removal of grazed grass for corn-fed cows. Milk yield and composition were recorded during the whole trial, in addition to indoor individual intake. Grass intake was modeled to calculate feed efficiency and estimate methane emissions. At the end of the experiment, bulk milk from each group was sampled for physicochemical and microbiological analyses and processed into Cantal-type cheeses. After 9 wk of ripening, cheeses underwent physicochemical, microbiological and descriptive sensory analyses. Results showed that the complete removal of grazed grass in corn-based system had no effect on milk production but impaired feed efficiency; grass reduction in the grass-based diet better maintained milk yield, enhanced feed efficiency, and reduced methane emission intensity. Cheese softness increased with proportion of grass in the diet, and it was positively correlated with primary proteolysis (alpha S1-casein and beta-casein breakdown) but negatively correlated with the C16:0/C18:1 ratio and the calculated fat melting point. Cheese from cows fed with more grazed grass were the yellowest and had the most pronounced flavors, as well as higher counts of heterofermentative lactobacilli and lactic acid bacteria. Removal of grazed grass from the corn-based diet led to cheese that was less yellow and had less flavor, in line with lower levels of secondary proteolysis. In conclusion, our study suggests that maintaining fresh herbage in corn-based diets is crucial for maintaining cheese quality without impairing animal performance. In grass-based systems, complementation with indoor feeding may have limited effects on product quality but promotes the maintenance of animal performance
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
Treatment-free remission in chronic myeloid leukemia with rare ABL1 gene fusions: real-life study from the French CML group Fi-LMC.
No full textInternational audienceTyrosine kinase inhibitors of the BCR::ABL1 oncoprotein can be stopped without subsequent molecular relapse or major safety concerns in 40 to 80% of adult patients with P210BCR::ABL1 positive chronic myeloid leukemia with sustained deep molecular responses. In contrast, ending treatment in patients with rare rearrangements located outside the major BCR region or within the exon 3 of ABL1 remains to be explored. Twenty-four patients with chronic phase disease and diverse uncommon BCR::ABL1 transcripts who obtained sustained molecular residual disease negativity and stopped therapy in a real-life setting for various reasons were retrospectively evaluated for treatment-free remission determinants. Six patients relapsed after a median time of 6 months (range; 3-49), relapse being defined as a rise in molecular residual disease above the 3-log threshold. Treatment-free remission probabilities at 12 and 60 months were 83.3% (95% CI: 68.4-98.2%) and 70.6% (95% CI: 49.5-91.6), respectively. The type of BCR::ABL1 transcript was the only relevant baseline factor associated with durable treatment-free remission and patients with fusions lacking exon a2 sequences had the best outcome. To conclude, treatment-free remission is a reasonably achievable goal in patients with rare ABL1 fusion transcripts. Our results pave the way for recommendations in clinical practice. Nevertheless, further research is needed to determine which patients have highest chances to reach deep molecular response levels and become free from therapy and to decipher the biological impact of the different molecular rearrangements of BCR::ABL1 on treatment-free remission
Real-Life Data of 2-Year Lumasiran Use in the DAILY-LUMA Cohort
No full textInternational audienceIntroduction: Lumasiran is a drug used in RNA-interference (RNAi) therapy for primary hyperoxaluria type 1 (PH1). Data on its efficacy and safety mainly come from industry-sponsored trials.Methods: For postmarketing follow-up, French authorities requested a quasi-exhaustive retrospective and prospective study over 5 years for patients receiving lumasiran, requiring the inclusion of at least 90% of patients, named as the DAILY-LUMA cohort (NCT06225882). Here, we analyzed data from all patients who were not previously included in the industry-sponsored trials and had received lumasiran for at least 2 years.Results: We included 38 patients, 22 from DAILY-A (i.e., estimated glomerular filtration rate (eGFR) > 45 ml/min per 1.73 m 2 , age $ 6 years), 6 from DAILY-B (i.e., eGFR > 45 ml/min per 1.73 m 2 , age < 6 years), and 10 from DAILY-C (i.e., all ages, eGFR < 45 ml/min per 1.73 m 2 , 6 on dialysis). In DAILY-A and DAILY-B, decreased urinary oxalate-to-creatinine (UOx/creat) ratio, stable eGFR, and decrease in both nephrocalcinosis severity and stone numbers were observed, with a progressive tapering of conservative therapies. The decreased proportion of patients with nocturnal hydration and G-tubes overtime likely reflects improved quality of life. With a low number of patients -2 patients on peritoneal dialysis and 3 patients with infantile oxalosisthe results are less conclusive for DAILY-C; however, in older patients, change in plasma oxalate (POx) levels is similar to previously published data. Tolerance was good with no severe side effects; injection site reactions, abdominal pain, and headaches were the main adverse events.</p
Élaboration de méthodologies de calcul en vue d’informer les consommateurs sur les dangers sanitaires et environnementaux des produits ménagers
No full textAnses. (2024). Élaboration de méthodologies de calcul en vue d'informer les consommateurs sur les dangers sanitaires et environnementaux des produits ménagers (Saisine 2021-SA-0231). Maisons-Alfort : Anses, 235 p.L’Anses a été saisie le 16 décembre 2021 par la Direction générale de la prévention des risques (DGPR), la Direction générale de la concurrence, de la consommation et de la répression des fraudes (DGCCRF), la Direction générale de la santé (DGS) et la Direction générale du travail (DGT) pour la réalisation de l’expertise suivante : élaboration d’une méthode de calcul permettant d’évaluer de façon globale la criticité des dangers sanitaires et environnementaux associés à l’utilisation des produits ménagers destinés aux consommateurs afin de renforcer la lisibilité de leurs étiquetages tel que prévu dans le cadre du quatrième plan national santé environnement (PNSE4).CONTEXTE ET OBJET DE LA SAISINELes attentes citoyennes sur les questions de santé-environnement sont de plus en plus fortes.Les consommateurs sont toujours plus attentifs à la qualité, l’origine et la composition des produits qu’ils achètent, notamment en ce qui concerne les substances chimiques. Les produits ménagers contiennent des substances chimiques dont certaines peuvent être néfastes pour la santé et / ou l’environnement.Les obligations en matière d'étiquetage pour informer les consommateurs sur la composition des produits du quotidien varient en fonction des types de produits et de leurs usages. Les informations en la matière, lorsqu’elles existent, sont, dans le cas général, peu - voire pas - lues par les consommateurs car souvent difficiles à interpréter.Dans ce cadre, parallèlement aux labels, différents types de scores ou de systèmes de notation ont vu le jour sur les produits du quotidien. Certains sont maintenant réglementés (exemple de l’étiquetage caractérisant l'émission des produits de construction), d'autres sont recommandés par le gouvernement et les institutions de recherche (exemples du Nutriscore ou de l’affichage environnemental1 sur les produits alimentaires (Férard et al. 2023)), ou par les institutions sanitaires (exemple du Composcore recommandé par le Haut conseil de la santé publique (HCSP) pour les produits de consommation (HCSP, 2020)). D'autres encore sont déployés par les industriels ou des associations de consommateurs et souvent disponibles via des applications (exemples Air label, score Leclerc).Le plan national santé-environnement 4 (PNSE4), publié le 7 mai 2021 par les ministères en charge de la santé et de l’écologie, prévoyait dans son action 3 de « renforcer la lisibilité de l’étiquetage des produits ménagers destinés aux consommateurs », afin de leur permettre de prendre rapidement des décisions éclairées. Le PNSE4 mettait en avant la pertinence d’une interprétation en termes simples, synthétiques et clairs de l’information exhaustive sur la composition de ces produits.Cette action du PNSE4 s’est notamment traduite par des travaux au sein d’un groupe de travail (GT) du Conseil national de la consommation (CNC), associant l’ensemble des parties prenantes (associations de défense des consommateurs, organisations professionnelles, administrations concernées) (CNC, 2021).Dans ce contexte, l’Anses a été saisie le 16 décembre 2021 par la DGPR, la DGCCRF, la DGS et la DGT afin de « poursuivre la mise en œuvre de l’action 3 du PNSE4, en élaborant une méthode de calcul qui permette d’évaluer de façon globale la criticité des dangers sanitaires et environnementaux associés à l’utilisation des produits ménagers destinés aux consommateurs, afin de renforcer la lisibilité de leurs étiquetages ».Les produits ménagers à considérer dans le périmètre de cette saisine et identifiés à partir du rapport du CNC portant sur l’amélioration de la lisibilité de l’étiquetage des produits ménagers destinés aux consommateurs (CNC 2021) sont :- les produits destinés à l’entretien du linge,- les produits destinés à l’entretien des surfaces,- les produits destinés à l’entretien des sanitaires,- les produits destinés à l’entretien de la vaisselle,- les insecticides / répulsifs / rodenticides,- les désodorisants d’atmosphère.Il a été demandé à l’Anses de s’appuyer, dans un premier temps, sur une analyse des initiatives, travaux et outils existants relatifs à l’impact de l’utilisation des produits ménagers sur la qualité de l’air intérieur ou à l’amélioration de l’information du consommateur. La méthode proposée doit tenir compte du niveau de préoccupation générée par les substances présentes dans les produits ménagers en raison de leurs dangers intrinsèques et de leurs concentrations. Les conditions d’utilisation décrites sur l’étiquette du produit, le mode d’utilisation (pulvérisation ou vaporisation, application sur une surface, type de surfaces à traiter, dosage, dilution, temps d’action, etc.), le cas échéant des profils d’utilisateurs spécifiques (grands consommateurs ou professionnels) et la ou les voies d’exposition devront également être prises en considération.Il est également demandé que l’Anses se prononce sur la faisabilité de développer une méthode de calcul fondée sur les risques liés à l’usage des produits ménagers.L’application de cette méthode de calcul devra permettre de catégoriser les produits ménagers destinés aux consommateurs afin que puisse être proposé, par Santé publique France (SpF), un étiquetage illustratif du niveau de vigilance et des recommandations à prendre en compte lors de l’usage de ces produits. La catégorisation de ces produits doit, en effet, conduire à faciliter la compréhension de l’ensemble des utilisateurs et notamment associer clairement les précautions d’usage à adopter pour ceux-ci.Enfin, le PNSE4 prévoyant que ces travaux conduisent à la mise en place d’un étiquetage illustratif de façon progressive et volontaire, il a été demandé à ce que l’Anses veille à l’élaboration d’une méthode de calcul simple à utiliser pour les acteurs économiques, notamment pour les petites et moyennes entreprises du secteur, et facilement contrôlable. À ce titre, il est recommandé que les travaux s’appuient sur des phases d’expérimentation de l’application de la méthode de calcul.Si cela s’avère pertinent, l’Anses a la possibilité de proposer plusieurs options pour la méthode de calcul, en mettant en avant les bénéfices et limites de chacune d’entre elles par rapport aux objectifs poursuivis
Secondary progression activity monitoring in MS despite an early highly active treatment the SPAM study
No full textInternational audienceBackground: Real-world data suggest that the early use of highly active therapies (HAT) may reduce the risk of transition to secondary progressive MS (SPMS). However, current knowledge about predictive factors of outcomes needs to be improved. The primary objective of this study was to determine factors associated with the occurrence of SPMS in patients treated early after MS onset with an HAT.Methods: Retrospective, multicentric study based on the French MS database. Patients who initiated a HAT within 5 years after MS onset, EDSS ⩽4, and had a follow-up >5 years were included. The association of each covariate at baseline with time to the occurrence of SPMS was quantified by hazard ratios (HRs) in unadjusted and adjusted Cox proportional hazards models.Results: Two thousand two hundred and thirty-seven patients were included in the analysis: mean age 31.6 years, female/male sex ratio 2.3, and median EDSS 2.0. The estimated probability of reaching SPMS, progression independent of relapse activity (PIRA) and progression independent of activity (PIA) at 10 years was 8%, 22%, and 11%, respectively. After adjustment, we found that female patients (HR 0.64, p = 0.036) had a lower risk of developing SPMS. Older age, EDSS >0 (HR 7.44, p < 0.001), and oral versus intravenous HAT (HR 1.97, p = 0.003) were significantly associated with an increased SPMS risk. Early PIRA and PIA predicted conversion to SPMS.Conclusions: Early HAT use resulted in a low risk of developing SPMS over 10 years. Introducing the HAT before any residual disability was associated with a lower risk of progression
Association of Diet With Treatment Response in Dogs With Chronic Enteropathy: A Retrospective Multicenter Study
No full textInternational audienceABSTRACT Background Hydrolyzed protein diets are commonly used in the first‐line approach to the treatment of dogs with naïve‐chronic enteropathy (naïve‐CE). Objectives To characterize the responses of naïve‐CE dogs transitioned to a hydrolyzed diet and to assess the efficacy of an additional dietary trial in dogs with NRE. Animals Eighty‐one dogs with naïve‐CE and 23 dogs with NRE. Methods Retrospective multicenter cohort study including dogs with CE presented to three referral centers from April 2018 to December 2021. Naïve‐CE and NRE cases transitioned to hydrolyzed and alternative diets, respectively, were selected, and medical records were reviewed. Clinical response before and 4 weeks after dietary transitions (with or without concurrent therapeutic adjustments) was assessed based on stool‐consistency score or Canine Inflammatory Bowel Disease Activity Index (CIBDAI) total score in naïve and NRE cases, respectively. Results The transition into a hydrolyzed diet was the only therapeutic change in 20% (16/81). Of these, 88% (14/16) had a decreased stool‐consistency score ( p < 0.001). From the 23 NRE cases, the transition to an alternative diet was the sole therapeutic adjustment in 70% (16/23). Of these, the total CIBDAI score declined in 69% (11/23; p < 0.001). Conclusions and Clinical Importance This study supports the need to feed a hydrolyzed diet in naïve CE cases. In cases classified as NRE, an additional transition into an alternative dietary trial seems beneficial
Clinical evidence for independent regulation of vitamin D by intestinal CYP24A1
No full textInternational audienc
A collar is a protective factor against early periprosthetic fracture for cementless stems in total hip arthroplasty
No full textInternational audienceAims Periprosthetic fractures (PPFs) are a significant complication in total hip arthroplasty (THA), with their incidence varying from 0.1% to 5.2% in registries. The use of a collared femoral stem may reduce the risk of PPF by enhancing the distribution of load and the stability of the implant. The aim of this study was to compare the effect of collared versus collarless stems on the incidence of PPFs in a large cohort of patients. Methods This retrospective study involved all primary THAs performed in a single centre between 1 January 2010 and 31 December 2020. Of the 2,182 THAs performed in 1,767 patients, 559 in 447 patients were excluded for the following reasons: having cemented stems, patients with a femoral neck fracture, dysplasia of the hip, or an oncological indication for surgery. A total of 1,623 THAs in 1,320 patients were included. The data which were collected included the patients’ demographics, the surgical approach, the implant characteristics, and the incidence of PPF. Univariate and multivariate analyses were conducted using the Bursac’s logistic regression model considering factors such as sex, age, BMI, surgical approach, and the presence of a collar. Results There were nine PPFs within 90 days of surgery: five in the collared stem group (0.4%) and four in the collarless stem group (1.6%). Multivariate analysis revealed that the presence of a collar was the only significant independent predictive factor of a reduced rate of PPFs (p = 0.048). Other factors such as sex, age, BMI, and surgical approach did not show significant correlations. Conclusion The collared stem was a protective factor against early femoral PPF when cementless stems were used in primary THA. These results support the preference for collared versus collarless cementless stems, particularly in patients who are at a high risk of PPF, to enhance the initial stabilty of the stem and reduce complications. Cite this article: Bone Joint J 2025;107-B(5 Supple A):70–75