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Profile of pregnant women complying or not with physical activity recommendations during the second trimester of pregnancy: a French pilot study
No full textInternational audienceInsufficient physical activity (PA) during pregnancy is a global public health concern. The aims of this study were: i) to determine retrospectively PA and sedentary time in women in the second trimester of pregnancy, and ii) to identify factors that influence adherence to the French National College of Midwives guidelines on PA (≥150 minutes of moderate to high-intensity PA per week). Methods: This cross-sectional, single-centre study, conducted at the University Hospital of Rennes, included 195 pregnant women. PA levels and sedentary time before and during the second trimester of pregnancy were determined using an anonymous self-report questionnaire. The self-reported PA levels were compared to the guidelines on PA. Bivariate analyses and Poisson generalized linear regression models were used to identify factors associated with non-compliance to such guidelines. Results: Only 30.7 % of pregnant women reported the recommended PA levels in the second trimester of pregnancy. Sedentary time and adherence to the PA guidelines were not associated. Fatigue was the most frequently cited reason for insufficient PA (71.6 %). Preconception PA level was the strongest predictor of adherence. Body mass index >25 kg/m², <2 years of higher education, limited access to transportation and sports facilities, and living in a town with <2.000 inhabitants also were associated with lower PA levels. Conclusion: Adherence to the PA recommendations is low among French pregnant women. Public health initiatives should emphasize PA importance before pregnancy and provide tailored support throughout gestation. Future studies should explore the interplay between PA, sedentary time and pregnancy outcomes
Investigating the effectiveness of an intraoperative decision support guided fluid therapy intervention on postoperative outcome of high-risk patients undergoing high-risk abdominal surgery: protocol for an international multicentre stepped-wedge cluster-randomised implementation trial
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Le programme-projet en psychiatrie de précision (PEPR PROPSY), enjeux et défis
No full textInternational audienceCurrent psychiatry, based on categorical descriptions of diagnostic entities, defined by international diagnostic manuals, is moving from this "one size fits all" strategy to a "precision psychiatry" that aims to be clinically informed by a dimensional, transdiagnostic perspective enriched by the use of objective, quantifiable and continuous markers such as omics, brain imaging, environmental and lifestyle variability of each individual. By recognizing the heterogeneity of existing categorical diagnostic entities, determined by the underlying biology, this approach aims to improve patient care. Precision medicine can be used to characterize and identify individuals with or at risk for a disorder, predict their prognosis, and make more specific choices of treatment strategies such as medications, psychological interventions, lifestyle rules, and/or brain stimulation, thereby improving prognosis and cost-effectiveness of the treatments.La psychiatrie actuelle repose sur des descriptions d’entités diagnostiques catégorielles. Ces entités sont définies par des manuels diagnostiques internationaux. La psychiatrie est en train d’évoluer d’une stratégie « one size fits all », vers une psychiatrie de précision. Cette nouvelle approche est éclairée par une perspective dimensionnelle sur le plan clinique. Elle prend en compte la variabilité génétique, environnementale et du mode de vie de chaque personne, et elle est enrichie par l’utilisation de marqueurs objectifs, quantifiables et mesurables. La médecine de précision pourra être utilisée pour caractériser et identifier les personnes atteintes ou à risque de développer une maladie. Elle permettra de prédire leur pronostic et elle aidera à faire un choix plus spécifique des stratégies thérapeutiques, comme par exemple, les médicaments, les interventions psychologiques, les règles d’hygiène de vie et/ou la stimulation cérébrale. Cette approche améliorera le pronostic et le rapport coût-efficacité des traitements
Switching from intravenous to subcutaneous infliximab is safe and feasible in patients with perianal Crohn’s disease
No full textInternational audienceBackground and objectives: We assessed the evolution of perianal lesions after switching intravenous (IV) to subcutaneous (SC) infliximab in patients with Crohn’s disease (CD). Design: Subgroup analysis of REMSWITCH studies. Methods: We described the clinical and MRI outcomes of patients with a prior or current CD perianal lesions after the switch. Results: In REMSWITCH, 40 CD patients had a prior history of perianal lesions. No patient experienced a new perianal lesion (median follow-up = 18 months). Among the three patients (3/40, 7.5%) with clinically active perianal lesions at baseline, two patients had no more perianal lesions at month 18 while the last patient experienced lesions worsening. Another one with active perianal lesions on MRI but no symptom at baseline did not have any relapse within 18 months. Only one patient (1/40, 2.5%) had a perianal relapse (at month 25) with remission recapture after SC infliximab intensification. Conclusion: Switching from IV to SC infliximab in CD with perianal lesions is safe and feasible
A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection: The Failure of a Procedure, not of a Therapy
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Transcriptomic analysis of human primary T cells after short-term leucine-deprivation and evaluation of kinase GCN2’s role in regulating differential gene expression
No full textInternational audienceChimeric Antigen Receptor T (CAR-T) cells offer a promising strategy for cancer treatment. These CAR-T cells are either autologous or allogeneic T cells that are genetically modified to express a chimeric antigen receptor targeting a specific tumor antigen. Ongoing research aims to optimize the CAR-T cell efficacy, including strategies to modulate their metabolism. One such approach involves inducing transgene expression by activating the GCN2 kinase signaling pathway through dietary deprivation of an essential amino acid. In this study, we investigated the general impact of a 6-hour leucine deprivation on primary activated human T cells using RNA-seq technology. Our analysis identified 3,431 differentially expressed genes between T cells cultured in regular medium and those cultured in leucine-deprived medium. Gene Set Enrichment Analysis revealed that “TNFα signaling via NFκB”, “interferon-γ response”, and “unfolded protein response” gene sets were positively enriched, while “mTORC1 signaling”, “Myc targets”, and “oxidative phosphorylation” gene sets were negatively enriched. To further evaluate the involvement of GCN2 kinase in regulating the differential gene expression during the 6-hour leucine deprivation, T cells were cultured with or without a GCN2 inhibitor. We found that 59% of the differentially expressed genes in our dataset were dependent on the kinase GCN2 (n = 2028), with 1,140 up-regulated and 888 down-regulated genes. These findings suggest a promising strategy to enhance CAR-T cell efficacy by combining short amino acid starvation with transient overexpression of a target gene
Necrotizing Enterocolitis in the newborn: a metabolic disturbance revealed by fecal volatolomics useful for diagnosis eight days before first symptoms
No full textP0649 Acceptability and Tolerance of Risankizumab Treatment Administered via On-Body Injector in Patients with Crohn’s Disease: Results of the Nationwide ACCEPT-OBI Study
No full textInternational audienceBackground Risankizumab (RZB) has been available in our country for Crohn’s disease (CD) patients through an early access program and is now administered using an innovative medical device known as an on-body injector (OBI). We assessed the acceptability and the tolerance of RZB administration via OBI and compare its acceptability with other modalities of CD treatments, and searched for factors associated with the OBI acceptability. Methods This was a prospective, multicenter longitudinal study. All CD patients from the early access cohort treated with RZB via OBI starting in February 2024 were assessed at the time of the switch to OBI (week 0 = W0) and at W8, W16, and W24. The primary endpoint was acceptability, evaluated using a acceptability numerical scale (ANS) ranging from 0 (completely unacceptable) to 10 (perfectly acceptable). Results A total of 58 multi-refractory patients were included (mean age : 42.8 ± 13.8 years; 57.9% were women, 17.3% were smokers, 64.7% had a history of intestinal resection, and 78.2% were in PRO2-clinical remission). Therapeutic education sessions were conducted concurrently for 36.2% (21/58) of patients. OBI was applied to abdomen, thigh, or another site in 43.9%, 52.6%, and 3.5% of patients, respectively. RZB administration via OBI was well tolerated in 57.4%, with possible mild application-site pain (20.4%, mild in 90% of cases), localized erythema (22.2%), pruritus (16.7%), edema (16.7%). No factors affected the acceptability of risankizumab administration via OBI in more than 15% of patients. RZB acceptability via OBI was very high (9.5 ± 1.2) at W0, significantly better than RZB subcutaneous injections (6.98 ± 2.57; p < 0.0001). OBI acceptability remained stable over time: 9.6 ± 1.2 at W8, 9.6 ± 1.4 at W16, and 9.6 ± 0.8 at W24 (p = 0.97). OBI acceptability as a medical device was better than other injectable administration modalities for IBD treatments: IV infusions (p < 0.0001), pen injectors (p < 0.001), and syringes (p < 0.001). Overall, patients preferred OBI (64.0%), followed by oral administration (28.0%), subcutaneous injections (6.0%), and IV infusions (2.0%). When adjusted for administration frequency, RZB every 8 weeks via OBI was the most preferred method (ANS = 9.2 ± 2.0), compared to long interval subcutaneous injections (every 12, 8, or 4 weeks), more frequent injections (weekly or eow), and IV infusions every 4–8 weeks (p < 0.001 for all comparisons). Conclusion In this cohort of refractory patients, the administration of risankizumab via OBI was highly acceptable to CD patients with excellent tolerance, suggesting that this new medical device could promote the use of risankizumab in clinical practice
LymphoTEC: a Retrospective Real-World Study on Lymphocyte Reconstitution After Lymphopenia in Patients with Multiple Sclerosis Treated with Dimethyl Fumarate in France
No full textInternational audienceIntroduction: Dimethyl fumarate (DMF) has demonstrated a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). Some patients may develop lymphopenia on DMF; therefore, LymphoTEC evaluated absolute lymphocyte count (ALC) reconstitution after DMF discontinuation.Methods: LymphoTEC was a retrospective, multicenter study of patients with RRMS in the Observatoire Français de la Sclérose en Plaques registry. Times to ALC reconstitution and lymphopenia were estimated by the Kaplan-Meier method. Univariate and multivariate analyses evaluated factors associated with ALC reconstitution after DMF discontinuation or lymphopenia after DMF initiation. Patients treated with DMF for ≥ 3 months with ≥ 1 ALC in the 6 months before/close to DMF initiation and ≥ 1 ALC during treatment were included.Results: Overall, 1429 RRMS patients were included; 356 patients developed lymphopenia, of whom 183 discontinued DMF. Overall, ALC decreased by 33% over the first year and plateaued thereafter. The probability of developing lymphopenia was 18.2% after 1 year. In patients with lymphopenia, median times to ALC reconstitution after DMF discontinuation were 3.8 months overall, 4.0 months for Grade 1 lymphopenia, 3.0 months for Grade 2, and 9.7 months for Grade 3. At 12 months, 83.0% had reconstituted ALC. In DMF discontinuers, median time to discontinuation was 1.2 years. There was no increased risk of serious or opportunistic infections in patients with lymphopenia. No cases of progressive multifocal leukoencephalopathy were reported. First ALC reconstitution after DMF discontinuation was associated with diabetes, DMF duration, DMF duration before lymphopenia, and DMF duration after lymphopenia; first lymphopenia after DMF initiation was associated with age and ALC at DMF initiation.Conclusion: LymphoTEC confirms previous reports on DMF-induced lymphopenia; the benefit-risk profile of DMF remains favorable. Most cases of lymphopenia were not severe and ALC reconstitution typically occurred within 4 months of DMF discontinuation. Patients with shorter and milder lymphopenia had faster ALC reconstitution.Trial registration: ClinicalTrials.gov NCT0475668
No genetic link between E. coli isolates carrying mcr-1 in bovines and humans in France
No full textInternational audienceColistin is a last-line antibiotic used to treat severe human infections caused by carbapenemase-producing Gram-negative bacteria. In parallel, colistin has massively been used in the veterinary field so that mcr-1 -positive E. coli have spread worldwide in livestock, potentially constituting a reservoir of colistin-resistant isolates that can be further transmitted to humans.Objectives: In France, the mcr-1 gene was frequently identified in E. coli of bovine origin. This genomic study assessed whether French human mcr-1 -positive E. coli might originate or derive from the bovine reservoir.Material and methods: Human (n = 24) and bovine (n = 127) isolates collected between 2011 and 2019 were included and colistin-resistance was confirmed by MICs. The detection of mcr-1 was performed by PCR. Isolates were short-read whole-genome sequenced and a cgMLST-based phylogeny was constructed. The genetic support of mcr-1 was identified using short-read sequences or Southern blots.Results: The mcr-1 gene was carried by a high diversity of genetic backgrounds, among which ST167 and ST10 were the most widespread. No clonally-related isolates between bovines and humans were observed. In bovines, mcr-1 was identified on IncHI2 and IncX4 plasmids and increasingly on the chromosome, while it was also found on IncI2 and p0111 plasmids in humans. Conclusion:Although similar STs (ST744 and ST88) and plasmid types (IncHI2, IncX4) carried mcr-1 , no hypothesis of a transfer from bovines to humans could be supported by the data. Furthermore, the increasing chromosomal location of mcr-1 over time may reflect an animal-specific evolutionary pathway deserving further investigation.</div