70 research outputs found

    A multicentric real-world observational study to describe the use and efficacy of follitropin delta for IVF/ICSI procedures in patients at risk of hypo-response

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    BackgroundAround 20% of patients undergoing assisted reproductive technology are at risk of hypo-response to ovarian stimulation. The aim of this study was to describe the real-world use of follitropin delta for ovarian stimulation in these patients, as defined by POSEIDON groups 3 and 4 [an anti-Müllerian hormone (AMH) level of <1.2 ng/ml].Materials and methodsThis study was a post-hoc analysis of participants from DELTA, a multi-centre, prospective, observational study conducted in normal care settings in fertility clinics at 14 active sites in France. A subset of 35 patients at risk of hypo-response to ovarian stimulation (mean AMH 0.7 ± 0.29 ng/ml) and treated with follitropin delta were included. Patients were followed for 10–11 weeks after the first fresh or frozen embryo transfer in case of subsequent pregnancy, and data on real-world follitropin delta use collected.ResultsMost patients (92.9%) had undergone their first IVF or ICSI. The prescribed daily dose was usually based on the approved algorithm (N = 26; 74.3%) with a mean daily dose of 14.2 ± 4.1 mcg, resulting in a mean total dose of 187.7 ± 135.6 mcg. The mean duration of ovarian stimulation was 11.6 ± 6.7 days with no premature discontinuations, while the mean number of oocytes retrieved among patients that started stimulation was 6.3 ± 4.3. A fresh transfer was performed for 21 patients (84.0%), with a mean of 1.04 ± 0.98 embryos transferred per patient. Seven patients (20.0%) achieved an ongoing pregnancy (28% per transfer). No adverse drug reactions were reported.ConclusionsThe results describe the real-world use of follitropin delta and demonstrate its suitability for POSEIDON group 3 and 4 patients. These data complement clinical trial outcomes, supporting clinician decision-making and improving IVF/ICSI outcomes

    Regional hippocampal vulnerability in early multiple sclerosis: a dynamic pathological spreading from dentate gyrus to CA1

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    "This is the peer reviewed version of the following article: Planche, V., Koubiyr, I., Romero, J. E., Manjon, J. V., Coupé, P., Deloire, M., ... & Tourdias, T. (2018). Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA 1. Human brain mapping, 39(4), 1814-1824., which has been published in final form at https://doi.org/10.1002/hbm.23970. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Background: Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. Method: We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. Results: At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R-2 = 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (beta = 0.87, p < .05). Conclusion: The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance.ARSEP Foundation; Bordeaux University Hospital; TEVA Laboratories; French Agence Nationale de la Recherche, Grant/Award Numbers: ANR-10-LABX-57, ANR-10-LABX-43, ANR-10-IDEX-03-02, ANR-10-COHO-002; UPV, Grant/Award Numbers: UPV2016-0099, TIN2013-43457-R; Ministerio de Economia y competitividadPlanche, V.; Koubiyr, I.; Romero Gómez, JE.; Manjón Herrera, JV.; Coupe, P.; Deloire, M.; Dousset, V.... (2018). Regional hippocampal vulnerability in early multiple sclerosis: a dynamic pathological spreading from dentate gyrus to CA1. 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Multiple Sclerosis Journal, 23(9), 1214-1224. doi:10.1177/1352458516675750Planche, V., Panatier, A., Hiba, B., Ducourneau, E.-G., Raffard, G., Dubourdieu, N., … Tourdias, T. (2017). Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis. Brain, Behavior, and Immunity, 60, 240-254. doi:10.1016/j.bbi.2016.11.010Planche, V., Ruet, A., Charré-Morin, J., Deloire, M., Brochet, B., & Tourdias, T. (2017). Pattern separation performance is decreased in patients with early multiple sclerosis. Brain and Behavior, 7(8), e00739. doi:10.1002/brb3.739Polman, C. H., Reingold, S. C., Banwell, B., Clanet, M., Cohen, J. A., Filippi, M., … Wolinsky, J. S. (2011). Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Annals of Neurology, 69(2), 292-302. doi:10.1002/ana.22366Rocca, M. A., Longoni, G., Pagani, E., Boffa, G., Colombo, B., Rodegher, M., … Filippi, M. (2015). 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    Neurol Neuroimmunol Neuroinflamm

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    BACKGROUND AND OBJECTIVES: Natalizumab, a monoclonal humanized antibody targeting integrin α4, inhibits the transmigration of lymphocytes into the CNS by preventing the interaction of integrin α4β1 with V-CAM expressed on brain vascular endothelial cells. Although natalizumab treatment reduces the clinical relapse rate in patients with relapsing-remitting MS, its discontinuation after reactivation of the JC virus is associated with a rebound of the disease in 20% of patients. The mechanisms of this rebound are not elucidated, but natalizumab increases the frequencies of circulating CD4 T cells expressing proinflammatory cytokines as well as the proportion of circulating Th17/Th1 cells (Th1-like Th17 cells). Gut-derived memory CD4 T cells are a population of growing interest in the pathogenesis of MS, but whether and how their properties are affected by natalizumab is not known. Here, we studied the phenotype and cytokine expression profile of circulating gut-derived memory CD4 T cells in patients with relapsing-remitting MS under natalizumab. METHODS: We identified gut-derived memory CD4 T cells by their expression of integrin β7 and compared their properties and those of integrin β7- memory CD4 T cells across healthy donors and patients with relapsing-remitting MS treated or not with natalizumab. We also compared the capacity of integrin β7- and integrin β7+ CD4 T-cell subsets to transmigrate in vitro across a model of blood-brain barrier. RESULTS: The proportions of proinflammatory Th17/Th1 cells as well as of IL-17A+IFNγ+ and IL-17A+GM-CSF+ cells were higher in memory CD4 T cells expressing integrin β7 in patients receiving natalizumab compared with healthy donors and patients with relapsing-remitting MS not receiving natalizumab. By contrast, integrin β7 negative memory CD4 T cells only presented a modest increased in their proportion of Th17/Th1 cells under natalizumab. We further observed that integrin β7+ Th17/Th1 cells migrated as efficiently as integrin β7- Th17/Th1 across a monolayer of brain microvascular endothelial cells. DISCUSSION: Our study shows that circulating integrin β7+ memory CD4 T cells of patients with relapsing-remitting MS under natalizumab are enriched in proinflammatory cells supporting the hypothesis that integrin β7+ memory CD4 T cells could play a pathogenic role in the disease rebound observed at natalizumab discontinuation. Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.Initiative d'excellence de l'Université de Bordeau

    Early cognitive impairment in multiple sclerosis predicts disability outcome several years later

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    Cognition is frequently impaired in the early stages of multiple sclerosis (MS). The predictive value of cognitive impairment on disability is unknown. The objective of this study was to correlate cognitive impairment and the progression of disability over 7 years. Forty-five patients, recruited after MS diagnosis, were followed for 7 years by yearly Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) evaluations and were classified as cognitively impaired (CI) or unimpaired (CU) according to neuropsychological testing at baseline. At baseline, 47.8% of patients were CI, with deficits in mainly memory and information processing speed (IPS). The baseline EDSS correlated significantly with one IPS test. The EDSS, but not the MSFC, deteriorated significantly over the 7 years in the whole group and the CI group, but not the CU group. A multivariate analysis showed correlations between the EDSS change over 5 and 7 years and two baseline tests evaluating IPS and verbal memory. The deterioration of the EDSS after 7 years was significantly correlated with verbal memory testing at baseline after adjustment for age and baseline EDSS. In conclusion, in this sample of MS patients early in the disease, the baseline IPS and verbal memory impairments predict the EDSS score 5 and 7 years later. </jats:p

    : MR and cognitive decline in RRMS

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    International audienceThe main predictors of cognitive changes over 7 years are baseline diffuse brain damage and progressive central brain atrophy over the 2 years after MS diagnosis

    A new computerised cognitive test for the detection of information processing speed impairment in multiple sclerosis

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    Background:Cognitive impairment in multiple sclerosis (MS) primarily applies to information processing speed (IPS).Objective:To evaluate psychometric properties of a new digit/symbol substitution test in healthy subjects and patients with MS, and assess its ability to detect IPS impairment in patients with MS.Methods:A sample of MS patients, 60 relapsing–remitting (RRMS) and 41 primary progressive MS (PPMS), and 415 healthy controls (HCs) underwent an IPS battery, including assessment of reaction times of subtests of the Test of Attentional Performance battery and a newly developed in-house digit/symbol substitution task, the Computerised Speed Cognitive Test (CSCT). The CSCT was additionally evaluated in a second cohort of 31 RRMS and 12 progressive MS patients, for comparison with the Symbol Digit Modalities Test (SDMT).Results:The CSCT had good reliability in both HCs and patients with MS. It showed a weak practice effect at the 6-month time point. This test had good ecological validity in MS patients. There was a strong correlation between the CSCT with the SDMT and with other IPS tests in patients with MS. The CSCT had the best sensitivity for predicting IPS impairment and was one of the most accurate tests among the IPS battery.Conclusion:The CSCT appeared as a good candidate for detecting IPS impairment in MS patients.</jats:sec

    Mult Scler.

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    Background: The Brief Computerized Cognitive Assessment in Multiple Sclerosis (BCCAMS) is a short neuropsychological battery for persons with multiple sclerosis (PwMS). Objectives: The main objective of the study is to validate the BCCAMS. Methods: PwMS and healthy subjects (HS) were evaluated using the BCCAMS which include two computerized tests, the Computerized Speed Cognitive Test and the Computerized Episodic Visual Memory Test (CEVMT), a newly developed visuospatial memory test, and the French learning test. The Minimal Assessment of Cognitive Function in MS (MACFIMS), including the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) tests, was also administered. Regression-based norms of the BCCAMS were calculated in 276 HS. BCCAMS was compared with BICAMS and MACFIMS for detection of cognitive impairment (CI). Results: Out of 120 PwMS, CI was detected using the BCCAMS, BICAMS (one impaired test), and MACFIMS (two impaired tests) in 59.1%, 50%, and 37.9%, respectively. The BCCAMS produced the same predictive value as that of the BICAMS battery for detecting CI in the MACFIMS. Conclusion: This study validated the BCCAMS as a validated computerized short assessment for information processing speed and learning in MS. © The Author(s), 2021

    Validation of a Brief Computerized Cognitive Assessment in Multiple Sclerosis (BCCAMS) and comparison with reference batteries

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    Background: The Brief Computerized Cognitive Assessment in Multiple Sclerosis (BCCAMS) is a short neuropsychological battery for persons with multiple sclerosis (PwMS). Objectives: The main objective of the study is to validate the BCCAMS. Methods: PwMS and healthy subjects (HS) were evaluated using the BCCAMS which include two computerized tests, the Computerized Speed Cognitive Test and the Computerized Episodic Visual Memory Test (CEVMT), a newly developed visuospatial memory test, and the French learning test. The Minimal Assessment of Cognitive Function in MS (MACFIMS), including the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) tests, was also administered. Regression-based norms of the BCCAMS were calculated in 276 HS. BCCAMS was compared with BICAMS and MACFIMS for detection of cognitive impairment (CI). Results: Out of 120 PwMS, CI was detected using the BCCAMS, BICAMS (one impaired test), and MACFIMS (two impaired tests) in 59.1%, 50%, and 37.9%, respectively. The BCCAMS produced the same predictive value as that of the BICAMS battery for detecting CI in the MACFIMS. Conclusion: This study validated the BCCAMS as a validated computerized short assessment for information processing speed and learning in MS. </jats:sec
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