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Identification des nouvelles cibles thérapeutiques potentielles pour le chc-mafld à unstade précoce de la fibrose par une approche « omique ».
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Identification de nouveaux marqueurs dans le CHC-MASLD selon les critères du degré de différenciation, de fibrose et de stéatose
No full textInternational audienceIntroductionLa stéatose hépatique d’origine métabolique (MASLD, Metabolic-dysfunctionAssociated Steatotic Liver Disease) constitue le premier stade des atteintesmétaboliques du foie. Cette stéatose peut progresser vers une stéatohépatite(MASH, Metabolic-dysfunction-Associated Steato-Hepatitis). Jusqu’en juin 2023, laMASLD et la MASH étaient respectivement nommées NAFLD et NASH [1]. Lesatteintes métaboliques du foie concernent aujourd’hui 25% de la populationmondiale, tous stades confondus. Précédemment, nous avons rapporté l'existencede 2 phénotypes de CHC-MASLD, par analyse de métabolomique, selon la sévéritéde la fibrose (F0F1 vs. F3F4) [2]. L’objectif de cette étude est d’explorer les voiesmétabolomiques impliquées dans la lipogenèse de novo (LDN), le métabolisme deslipides (ML), l’oxydation des acides gras (FAO), la glycolyse (GLY), et le métabolismedes acides aminés à chaîne ramifiée (BCAA), dans le but d’identifier desbiomarqueurs tissulaires du CHC-MASLD en fonction de trois critères : sévéritéde fibrose (F0F1 vs. F3F4), degré de différenciation (bien différencié vs.moyennement différencié) et le grade de stéatose (modéré vs. sévère).Matériels et MéthodesNotre cohorte comprend 56 paires de tissus hépatiques humains, tumoraux (TT) etnon-tumoraux (NTT) (F0F1 = 28, F3F4 = 28). Une analyse par qRT-PCR portant surl'expression de 34 gènes impliqués dans les voies métaboliques (LDN, ML, FAO, GLY,BCAA) a été effectuée (Tableau 1). Pour chaque groupe, le CHC a été comparé àson propre NTT ainsi qu’aux tissus hépatiques sains.RésultatsLes résultats de l'analyse transcriptomique d’un panel de 34 gènes montre que :1-Selon le degré de fibrose (F0F1 vs. F3F4), les CHC-MASLD diffèrent par une uprégulation de l’expression de 3 gènes impliqué respectivement : dans la synthèse desphospholipides (up-régulation de la choline kinase (CHKA) dans les CHC F0F1), enrevanche l’up-régulation de ACADS impliquée dans l’oxydation des acides gras àchaines courtes et de FBP1 impliquée dans la glycolyse concerne exclusivement lesCHC F3F4 (Figure1, Tableau 1). Ces données confirment l'existence de deuxphénotypes de CHC-MASLD selon la sévérité de fibrose [2].2- En fonction du degré de différenciation (CHC-MASLD bien différencié vs. CHCMASLD moyennement différencié). Les CHC-MASLD diffèrent par l’expression de 2gènes codant respectivement pour SGSM2, (phospholipase catalysant l’hydrolyse dela sphingomyéline en céramide), et MBOAT7, (impliquée dans la production duphosphytidylinositol et de l’acide arachidonique). L’expression de ces 2 gènes estup-régulée dans les CHC-MASLD caractérisés avec un degré de différenciationmoyenne. Ces observations suggèrent que MBOAT7 serait un candidat-marqueurdans le CHC-MASLD avec une fibrose minime associé à un degré de différenciationmoyen alors que SGMS2 serait un marqueur exclusif des CHC-MASLD avec un stadede différenciation moyen. (Figure1, Tableau 1).3- Selon le degré de stéatose, nos analyses comparatives montrent quel’expression du gène codant pour l’isoforme ACC2, enzyme mitochondriale impliquéedans la première étape de la LDN, est up-régulée exclusivement dans les CHCMASLD présentant un degré de stéatose sévère (Figure1, Tableau 1). Ce résultatindiquerait que l’expression de l’isoforme ACC2 pourrait servir de marqueur dans lesCHC-MASLD avec une stéatose sévère. Nos résultats renforcent les observations del’étude utilisant l’inhibiteur d'ACC (GS-0976) dans la NASH [3].ConclusionLes analyses transcriptomiques de cette étude permettent de : i) discriminer lesphénotypes des CHC-MASLD selon la sévérité de fibrose, du degré de différenciationet de la stéatose ii) proposer 6 marqueurs non-invasifs: CHKA, ACADS, FBP1,MBOAT7, SGSM2 et ACC2 pour le CHC-MASLD en fonction de ces 3 critères iii) Cesobservations pourraient ouvrir la voie à des applications cliniques comme l’utilisationdes inhibiteurs de l'AAC2 en association aux inhibiteurs de tyrosine kinase oul’immunothérapie dans les CHC-MASL
Clinical, paraclinical and outcome features of 166 patients with acute anti-GQ1b antibody syndrome
No full textInternational audienceBackground & purpose: In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies. Results: We identified 166 patients with neurological symptoms appearing in less than 1 month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50 years (4u201390), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillainu2013Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1 year follow-up. One patient died, and 15% of patients relapsed. Age > 70 years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12 months. No predictors of relapse were identified. Conclusion: This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses
Avis de l’Anses relatif à un cas d’hallucinations en lien avec la consommation du complément alimentaire Novanuit® Triple Action
No full textCitation suggérée : Anses. 2023. Avis de l’Anses relatif à « un cas d’hallucinations en lien avec la consommation du produit Novanuit® Triple Action » (saisine 2023-VIG-0188). Maisons-Alfort : Anses. 22 p.Dans le cadre de son dispositif de nutrivigilance créé en 2009, l’Anses a reçu un signalement d’effet indésirable sévère (sévérité de niveau 3)1 susceptible d’être lié à la consommation du produit Novanuit® Triple Action commercialisé en France par la société Opella Healthcare France. Ce cas, enregistré dans la base de données de nutrivigilance sous le numéro 2023-060 a été jugé d’imputabilité très vraisemblable.En raison de la sévérité de l’effet indésirable rapporté (hallucinations et confusion), l’Anses s’est autosaisie le 19 octobre 2023, estimant nécessaire de porter ce cas à la connaissance du public, des metteurs en marché et des professionnels de santé, dans un but d’amélioration de la sécurité sanitaire du consommateur
Is large for gestational age in singletons born after frozen embryo transfer associated with freezing technique or endometrial preparation protocol? A longitudinal national French study
No full textInternational audienceAbstract STUDY QUESTION Is large for gestational age (LGA) observed in babies born after frozen embryo transfer (FET) associated with either the freezing technique or the endometrial preparation protocol? SUMMARY ANSWER Artificial cycles are associated with a higher risk of LGA, with no difference in rate between the two freezing techniques (vitrification versus slow freezing) or embryo stage (cleaved embryo versus blastocyst). WHAT IS KNOWN ALREADY Several studies have compared neonatal outcomes after fresh embryo transfer (ET) and FET and shown that FET is associated with improved neonatal outcomes, including reduced risks of preterm birth, low birthweight, and small for gestational age (SGA), when compared with fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology of this increased risk remains unclear; parental infertility, laboratory procedures (including embryo culture conditions and freezing-thawing processes), and endometrial preparation treatments might be involved. STUDY DESIGN, SIZE, DURATION A multicentre epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national register of IVF from 2014 to 2018, including single deliveries resulting from fresh ET or FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres and included the vitrification media and devices, and the endometrial preparation protocols. PARTICIPANTS/MATERIALS, SETTING, METHODS Data were collected from 35 French ART centres, leading to the inclusion of a total of 72 789 fresh ET, 10 602 slow-freezing FET, and 39 062 vitrification FET. Main clinical outcomes were presented according to origin of the transferred embryos (fresh, slow frozen, or vitrified embryos) and endometrial preparations for FET (ovulatory or artificial cycles), comparing five different groups (fresh, slow freezing-ovulatory cycle, slow freezing-artificial cycle, vitrification-ovulatory cycle, and vitrification-artificial cycle). Foetal growth disorders were defined in live-born singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if <10th and ≥90th percentiles, respectively. Analyses were performed using linear mixed models with the ART centres as random effect. MAIN RESULTS AND THE ROLE OF CHANCE Transfers led to, respectively, 19 006, 1798, and 9195 deliveries corresponding to delivery rates per transfer of 26.1%, 17.0%, and 23.5% after fresh ET, slow-freezing FET, and vitrification FET, respectively. FET cycles were performed in either ovulatory cycles (n = 21 704) or artificial cycles (n = 34 237), leading to 5910 and 10 322 pregnancies, respectively, and corresponding to pregnancy rates per transfer of 31.6% and 33.3%. A significantly higher rate of spontaneous miscarriage was observed in artificial cycles when compared with ovulatory cycles (33.3% versus 21.4%, P < 0.001, in slow freezing groups and 31.6% versus 21.8%, P < 0.001 in vitrification groups). Consequently, a lower delivery rate per transfer was observed in artificial cycles compared with ovulatory cycles both in slow freezing and vitrification groups (15.5% versus 18.9%, P < 0.001 and 22.8% versus 24.9%, P < 0.001, respectively). Among a total of 26 585 live-born singletons, 16 413 babies were born from fresh ET, 1644 from slow-freezing FET, and 8528 from vitrification FET. Birthweight was significantly higher in the FET groups than in the fresh ET group, with no difference between the two freezing techniques. Likewise, LGA rates were higher and SGA rates were lower in the FET groups compared with the fresh ET group whatever the method used for embryo freezing. In a multivariable analysis, the risk of LGA following FET was significantly increased in artificial compared with ovulatory cycles. In contrast, the risk of LGA was not associated with either the freezing procedure (vitrification versus slow freezing) or the embryo stage (cleaved embryo versus blastocyst) at freezing. Regarding the vitrification method, the risk of LGA was not associated with either the vitrification medium used or the embryo stage. LIMITATIONS, REASONS FOR CAUTION No data were available on maternal context, such as parity, BMI, infertility cause, or maternal comorbidities, in the French national database. In particular, we cannot exclude that the increased risk of LGA observed following FET with artificial cycles may, at least partially, be associated with a confounding effect of some maternal factors. No information about embryo culture and incubation conditions was available. Most of the vitrification techniques were performed using the same device and with two main vitrification media, limiting the validity of a comparison of risk for LGA according to the device or vitrification media used. WIDER IMPLICATIONS OF THE FINDINGS Our results seem reassuring, since no potential foetal growth disorders following embryo vitrification in comparison with slow freezing were observed. Even if other factors are involved, the endometrial preparation treatment seems to have the greatest impact on LGA risk following FET. FET during ovulatory cycles could minimize the risk for foetal growth disorders. STUDY FUNDING/COMPETING INTEREST(S) This work has received funding from the French Biomedicine Agency (Grant number: 19AMP002). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER N/A
DISP1 deficiency: monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations
No full textInternational audiencePURPOSE: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog (SHH), a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and midline craniofacial malformations. The objective of the present study was to better delineate the clinical phenotypes associated with DISP1 variants. METHODS: This study was based on the identification of at least one pathogenic variant of the DISP1 gene in individuals for whom detailed clinical data were available. RESULTS: A total of 23 DISP1 variants were identified in heterozygous, compound heterozygous or homozygous states in 25 individuals with midline craniofacial defects. Most cases were minor forms of HPE, with craniofacial features such as orofacial cleft, solitary median maxillary central incisor (SMMCI), and congenital nasal pyriform aperture stenosis (CNPAS). These individuals had either monoallelic loss-of-function variants or biallelic missense variants in DISP1. In individuals with severe HPE, the DISP1 variants were commonly found associated with a variant in another HPE-linked gene (i.e. oligogenic inheritance). CONCLUSION: The genetic findings we have acquired demonstrate a significant involvement of DISP1 variants in the phenotypic spectrum of midline defects. This underlines its importance as a crucial element in the efficient secretion of SHH. We also demonstrated that the very rare SMMCI-CNPAS combination is part of the DISP1-related phenotype. The present study highlights the clinical risks to be flagged up during genetic counseling after the discovery of a pathogenic DISP1 variant
Six-year follow-up of phase II study exploring chemo-free treatment association with idelalisib and obinutuzumab in symptomatic relapsed/ refractory patients with Waldenström’s macroglobulinemia
No full textInternational audienceWe present the 6-year update of a phase 2 study evaluating the combination of obinutuzumab and idelalisib in relapse/refractory Waldenstrom macroglobulinemia. The results of the REMODEL trial demonstrated interesting efficacy in a high-risk genotype profile population. The primary endpoint was achieved with a median PFS of 25.4 months (95% CI, 15.7 to 29.0). However, a major limitation of idelalisib is its toxicity. With a median follow-up of 70.9 months, median OS was still not reached, and 5-year OS was 72.9% (95% CI, 61.3 to 86.6). We confirm that CXCR4 mutations had no impact on PFS or OS. However, TP53 mutated patients had shorter OS. At the time of analysis, six patients are alive without relapse and 40 had progressive disease. Among the 38 patients who received a new treatment, the median time to second progression was not reached in ibrutinib treated patients (n = 17) versus 30.8 months in patients treated with other options (95% CI, 16.9 to NA), p = 0.005. With longer follow-up our prospective study is the first to show an impact of TP53 mutations in patients treated with fixed duration chemo-free regimen leading to a significant shorter OS in this population. Moreover, ibrutinib remains an effective treatment after this combination. This study was registered on the clinicaltrial.gov web (NCT02962401, November 9, 2016)
Prevalence of Congenital Ocular Anomalies in 15 Countries of Europe: Results From the Medikeye Study
No full textInternational audienceBackground: Congenital ocular anomalies (COA) are among the most common causes of visual impairment in children in high-income countries. The aim of the study is to describe the prevalence of the various COA recorded in European population-based registries of CA (EUROCAT) participating in the EUROmediCAT consortium.Methods: Data from 19 EUROmediCAT registries and one healthcare database (EFEMERIS) were included in this descriptive epidemiological study. Cases of COA included live births, FD from 20 weeks gestational age (GA), and termination of pregnancy for fetal anomaly.Results: The prevalence of total COA was 3.47/10,000 births (95% CI [3.61-3.82]), ranging from 1.41 to 13.46/10,000 depending on the registry. Among COA cases, congenital lens anomalies were the most frequent anomalies (31%), of which over half were single ocular anomalies (presenting with only one ocular anomaly). An/microphthalmia was the second most frequent COA (24%) of which three-quarters were multiply malformed (associated to extraocular major anomalies). Among single COA cases, 58 were prenatally diagnosed (4%), of which, 58% were diagnosed in the second trimester. Known genetic causes of COA explained 2.5%-25% of COA depending on their class.Conclusions: This is the first European study describing COA. The detailed prevalence data offered in this study could improve screening and early diagnosis of different classes of COA. As COA are rare, epidemiological surveillance of large populations and accurate clinical descriptions are essential
La satisfaction des femmes vis à vis de l'entretien postnatal précoce
No full textThe early postnatal interview recently completes the medical follow-up of women in postpartum, since July 2022. This required interview was set up following dissatisfaction of women during their follow-up in postpartum. The reducing of the stay in maternity, the weak practice of birth training in postpartum as well as the late occurrence of the postnatal consultation favored its development.This descriptive observational quantitative study aims to assess the satisfaction of women during early postnatal interviews. It must also define their needs. A self-questionnaire was distributed between September 2023 and February 2024 in four liberal cabinets in the Auvergne-Rhône-Alpes region as well as on parent groups on the social network Facebook. It was analyzed using Microsoft Excel and Jamovi software.The results show that women are satisfied when the form of the interview respect the recommendations of the CNSF. It must be a time of exchange in the company of the newborn and the partner. Women need to express their emotional well-being since giving birth and returning home.Encourage their parenting skills is necessary to allow a new family balance. Nevertheless, it is important to develop communication around the interview. As many women as possible must benefit from this interview. Therefore, health professionals must be aware of the importance of its practice, since it proves to be a good prevention plan.L’entretien postnatal précoce complète nouvellement le suivi des femmes depuis juillet 2022. Cet entretien obligatoire a été mis en place suite au mécontentement des femmes lors de leur suivi en post-partum. Le raccourcissement du séjour en maternité, la faible pratique des séances de préparation à la naissance en post-partum ainsi que la survenue tardive de la consultation postnatale ont favorisé son développement.Cette étude quantitative observationnelle descriptive a pour objectif d’évaluer la satisfaction des femmes lors de l’entretien postnatal précoce. Elle doit aussi définir leurs besoins lors de celui-ci. Un auto-questionnaire a été distribué entre septembre 2023 et janvier 2024 dans quatre cabinets libéraux de la région Auvergne-Rhône-Alpes ainsi que sur des groupes de parents sur le réseau sociale Facebook. Il a été analysé à l’aide des logiciels Microsoft Excel et Jamovi.Les résultats démontrent que les femmes sont satisfaites lorsque les modalités de l’entretien respectent les préconisations du CNSF. Il doit être un temps d’échange en compagnie du nouveau-né et du coparent. Les femmes ont besoin d’exprimer leur bien-être émotionnel depuis leur accouchement et retour à domicile.Favoriser leurs compétences parentales est nécessaire pour permettre un nouvel équilibre familial.Il reste néanmoins, important de développer la communication autour de l’entretien, de telle sorte qu’un maximum de femme puisse en bénéficier. Les professionnels de santé doivent donc être sensibilisés à l’importance de sa pratique, puisqu’il s’avère être un bon outil de prévention
L’impact du suivi en ergothérapie sur l’aidant familial d’une personne déficiente visuelle
No full textIntroduction: the family caregivers represent 15% of the French population, i.e. almost 9.3 million of people. This status creates a lot of consequences on their health, to the point of becoming a public health issue. Occupational therapists, through their skills, have been identified as major actors in maintaining their quality of life. The aim of this study is to assess the impact of occupational therapy care on the family caregivers of visually impaired people. Methods: a survey using the Caregiver Reaction Assessment scale was sent to associations and structures specialising in low vision. A statistical analysis, with the Wilcoxon and Kruskal Wallis test was used to compare the quality of life before and after the intervention of the occupational therapist. Results: 32 family caregivers responded to the questionnaire. Occupational therapy significantly improved the perceived quality of life (p < 0.05) regarding the burden on free time and activities for spouses (3.9±0.55 vs. 3.4±0.56) and for parents (3.9±1.08 vs. 3.8±1.07). Conclusion: in general, the family caregivers perceived a better quality of life following the intervention of the occupational therapist. The occupational therapist’s consideration of the needs and the difficulties faced by the family caregivers are some of the most important factors to improve their quality of life.Introduction : les aidants familiaux représentent 15 % de la population française, soit près de 9,3 millions de personnes. Ce statut engendre de multiples conséquences sur leur santé, au point d’être devenu un véritable problème de santé publique. L’ergothérapeute, de par ses compétences, est identifié comme un acteur majeur dans le maintien de leur qualité de vie. L’objectif de cette étude est d’évaluer l’impact des prises en charge en ergothérapie sur les aidants familiaux de personnes déficientes visuelles.Méthodes : un questionnaire utilisant l’échelle Caregivers Reaction Assessment (échelle de la réaction du proche) a été envoyé à différentes associations et structures spécialisées en basse vision. Une analyse statistique avec le test de Wilcoxon et celui de Kruskal Wallis a été effectuée pour comparer la qualité de vie ressentie avant et après l’intervention de l’ergothérapeute.Résultats : 32 aidants familiaux ont répondu au questionnaire. L’ergothérapie améliore de manière significative (p < 0,05) la charge sur le temps libre et les activités chez les conjoints (3,9 ± 0,55 vs. 3,4 ± 0,56) et les parents (3,9 ± 1,08 vs. 3,8 ± 1,07). Conclusion : d’une manière générale, les aidants familiaux ressentent une meilleure qualité de vie à la suite des interventions de l’ergothérapeute. La prise en compte par l’ergothérapeute des besoins et difficultés rencontrés par l’aidant font partie des facteurs les plus importants pour améliorer leur qualité de vie