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Evaluation of ZT Scan DIA for the diagnosis of bloodstream infections
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Chronic pain in older adults with psychiatric disorders: the DoCPPA study protocol
No full textInternational audienceAbstract Background Chronic pain (CP) and psychiatric disorders (PD) are common in older adults, and they both may significantly impact patients’ functioning and quality of life. However, research on the prevalence and impact of CP in people with PD remains limited– especially in older adults– and psychiatric care often neglects somatic comorbidities. Objectives The main objective of the DoCPPA study is to determine the prevalence and characteristics of CP in older adults with PD followed-up in psychiatric services. Our secondary objective is to estimate associations between CP and various clinical indicators related to physical, cognitive, and mental health, as well as quality of life. Setting Department of Aging Psychiatry of Le Vinatier Hospital Center (France, Bron), inpatient and outpatient psychiatric services. Method/design Cross-sectional monocentric study with 430 patients with PD under psychiatric care. The inclusion period will be 36 months. The patients will be evaluated using validated scales and neuropsychological assessments. Discussion This study aims to contribute to improving care in aging psychiatry, a field where a major challenge lies in the management of multiple chronic conditions
A Comprehensive Study of the Cobalt(II) Chelation Mechanism by an Iminodiacetate-Decorated Disaccharide Ligand
No full textInternational audienceWe report an investigation on the cobalt(II) chelation mechanism by a modified α-maltoside ligand 9 decorated with two iminodiacetate (IDA) residues on C6,C6 ′ positions. Herein we uncovered the capacity of this biodegradable ligand to chelate cobalt(II), an ionic metal contaminant in the environment that is used, in particular, in lithium-ion batteries. The interactions between cobalt(II) and synthesized ligand 9 were systematically studied using different analytical methods such as 1 H and 13 C NMR, potentiometry, spectrophotometry, ITC, and ICP-AES. We observed a high affinity for the 1:1 complex, one cobalt(II) associated with two iminodiacetate groups, which is 10-fold higher than the 2:1 complex, where each of the two IDA groups interacts alone with a cobalt(II). Taking into account the log β CoL value obtained (≈12.3) with the stoichiometry 1:1, the strength of this complexation with cobalt(II) can be ranked as follows for the most common ligands: IDA < MIDA < NTA < 9 < EDTA < TTHA < DTPA. We further completed a preliminary remediation test with water contaminated with cobalt(II) and recovered cobalt(II) metal using Chelex ® resin, which allowed a recycling of the synthetic ligand for future recovering experiments. The results shed light on the great potential of using this synthetic ligand as an effective and green remediation tool
International real-world study of combination immunotherapy sequences in metastatic melanoma
No full textInternational audienceBackground Immune checkpoint inhibitors (ICIs) have revolutionized melanoma treatment, with programmed cell death protein 1 (PD-1) inhibitors—alone or in combination with cytotoxic T-lymphocyte–associated protein 4 or lymphocyte-activation gene 3 inhibitors—demonstrating significant efficacy. However, there is a critical lack of robust data to determine the optimal sequencing of these therapies for individual patients. In particular, the role of relatlimab+nivolumab (rela/nivo) within treatment sequences remains poorly defined. Choosing the right sequence is strategic, as an inappropriate order may compromise the effectiveness of subsequent treatments and limit long-term benefits. Methods This multicenter retrospective and prospective study evaluated 190 patients across three treatment arms: rela/nivo followed by ipilimumab+nivolumab (ipi/nivo) (arm A, N=40), ipi/nivo followed by rela/nivo (arm B, N=71), and anti-PD-1 followed by rela/nivo (arm C, N=79). The study assessed the impact of treatment sequencing on outcomes including response rate, progression-free survival, and overall survival (OS). Results The overall response rate to second treatment was highest in arm C (30.4%), followed by arm B (28.1%) and arm A (17.5%). Patients with secondary resistance to first-treatment ICIs had better responses to second-treatment ICIs than those with primary resistance, particularly in arm B (p=0026). Median OS from date of first ICI treatment was significantly longer in arms B (40.9 months) and C (42.5 months) compared with arm A (16.3 months). Conclusions Our findings indicate that rela/nivo may remain active following anti-PD-1 or ipi/nivo therapy. Additionally, our results suggest that sequencing ipi/nivo before rela/nivo may yield better outcomes than starting with rela/nivo. Patients who respond to the first combination regimen appear to derive greater benefit from the second. Further efforts are needed to optimize sequencing strategies in advanced melanoma, and future studies should consider the impact of prior treatment outcomes
Effectiveness of Different Methods of Interdental Hygiene in Daily Practice Among Young Adults: Protocol for a Randomized, Single-Blind Controlled Trial
No full textInternational audienceBackground Interdental spaces are particularly susceptible to biofilm accumulation and gingival inflammation, which contribute to periodontal diseases and their systemic associations. While interdental brushes (IDBs) are recognized as the most effective method of interdental cleaning, their efficacy depends on proper adaptation to the interdental space. Calibration with a colorimetric probe may enhance their effectiveness and comfort. However, evidence directly comparing calibrated and noncalibrated IDBs, especially in young adults, a key target group for preventive strategies, remains limited. The Hygiene of Interdental Junctions in Adults (HIJA) trial was designed to address this gap. Objective This protocol aims to compare the clinical, microbiological, and acceptability outcomes associated with calibrated versus noncalibrated IDBs in young adults, focusing on interdental inflammation, periodontal indices, and microbiota composition. Methods The HIJA trial is a monocentric, randomized, controlled, single-blind, and parallel-arm study. Overall, 50 healthy, nonsmoking adults aged 18‐30 years will be randomized (1:1) to receive either calibrated or noncalibrated IDBs. Participants will perform daily interdental cleaning in addition to conventional toothbrushing for 3 months. The primary outcome will be the reduction in interdental inflammation, expressed as the change in bleeding on probing at 3 months. Secondary outcomes will assess differences in interdental microbiota composition (16S ribosomal RNA sequencing), periodontal indices (plaque index, gingival index, probing depth, and clinical attachment loss), and user acceptability measured through the Theoretical Framework of Acceptability questionnaire at 1, 2, and 3 months. Results The HIJA trial will generate evidence on whether calibrated IDBs provide additional benefits over noncalibrated brushes in reducing interdental inflammation and improving oral health in young adults. Conclusions HIJA findings could contribute to the implementation of clinical guidelines and preventive strategies for interdental hygiene in daily practice
Impact of midostaurin in younger AML patients intensively treated with high-dose anthracycline
No full textInternational audienceIntroduction: Midostaurin (MIDO) was approved by the FDA in 04/2017 for the treatment of FLT3 mutated AML patients in combination with intensive chemotherapy (ICT) with daunorubicin (DAUNO) administered at 60 mg/m² for 3 days based on the findings of the RATIFY trial (Stone, NEJM 2017). Moreover, the UK NCRI AML17 trial (Burnett, Blood 2016) demonstrated that higher DAUNO exposure at 90 mg/m² (without MIDO) provided a particular benefit for patients with FLT3 mutated AML. The aim of this post-hoc study was to assess the impact of MIDO in combination with higher-dose anthracyclines (DAUNO or idarubicin) in the BIG-1 trial (Hunault, NEJM Ev 2025). Methods: Between 01/2015 and 07/2021, the BIG-1 trial (NCT02416388) included patients (pts) aged 18-60 years with newly diagnosed AML treated with ICT (CBF-AML and APL excluded). DNA fragment analysis (FA) detected FLT3-ITD (AR≥0.05 for positivity) and FLT3-TKD mutations were detected depending on each center's usual procedures. The protocol planned single and first induction cycle containing anthracycline. Pts may receive either DAUNO (90 mg/m², d1-3) or idarubicin (9 mg/m², d1-5), combined with cytarabine 200 mg/m² (d1-7). After its approval, MIDO has been introduced in 07/2018 during the course of the trial and provided by Novartis. This offered the opportunity to assess the role of MIDO in this context using an internal control group. Of note, MIDO was omitted during the post-induction cycles in the few pts who entered nested randomized studies evaluating dexamethasone (N=46) or vosaroxin (N=13) in combination with HDAC or IDAC, respectively. Results: Overall, 382 (84.7%) pts had FLT3-ITD, 83 (18.4%) had a TKD mutation and 14 had both, leading to the inclusion of 451 pts in this analysis. 282 (62.5%) pts received ICT without MIDO (ICT group: internal control) and 169 (37.4%) received ICT with MIDO (ICT+MIDO group). Median age was 50.1y and 263 pts were female. ELN-2022 genetic risk was favorable, intermediate and adverse in 49 (10.9%), 319 (70.7%) and 77 (17.1%) pts. 302 (67%) pts carried also a NPM1 mutation without significant differences between the two groups. Following induction, the rate of CR/CRi was 77.3% vs 88.7% in ICT vs ICT+MIDO groups (p=0.002), respectively. Early death rate at d30 was 4.3% vs 1.2% (p=0.006). After adjustment on confounding factors including allo-HSCT in CR1 as a time-dependent variable in multivariate analysis, MIDO was significantly and independently associated with a decreased risk of relapse (sHR 0.63 [0.46-0.85]; P=0.003). At 2 and 5 years, cumulative incidence of relapse (CIR) was 43.6% vs 35% and 48.1% vs 40.9%, in the ICT and ICT+MIDO group respectively. The two other independent predictive factors for relapse were ELN-2022 genetic risk and allo-SCT in CR1 as protective factor. Anthracycline, gender, age and WBC did not significantly influence CIR. MIDO was also significantly and independently associated with a decreased risk of death or relapse (aHR 0.74 [0.55-0.98]; P=0.036), as well as ELN-2022 genetic risk and allo-SCT in CR1. At 2 and 5 years, RFS was 49.7% vs 55.4% and 42.5% vs 46.4%, in the ICT and ICT+MIDO group respectively. Again, anthracycline, gender, age and WBC did not significantly influence RFS. MIDO was significantly and independently associated with a decreased risk of death, relapse or failure (aHR: 0.65 [0.50-0.84]; P=0.001), as well as WBC, ELN-2022 genetic risk and allo-SCT in CR1. At 2 and 5 years, EFS was 43.3% vs 54.2% and 37.6% vs 44%, in ICT and ICT+MIDO groups respectively. Anthracycline, gender and age did not significantly influence EFS. Finally, MIDO was significantly and independently associated with a decreased risk of death (aHR: 0.70 [0.50-0.96]; P=0.02), as well as WBC, age and ELN-2022 genetic risk but neither allo-HSCT in CR1, nor sex, nor the type of anthracycline was associated with OS. At 2 and 5 years, OS was 62.8% vs 73.2% and 52.8% vs 62%, in ICT and ICT+MIDO group respectively. Conclusion: Subject to the limitations of this non-randomized study, adding MIDO to high-dose anthracycline-based chemotherapy improves CIR, RFS, EFS and OS independently of other factors, resulting in notable 5-year cure rates
Serotonergic dysfunction in patients with impulse control disorders in Parkinson’s disease
No full textInternational audienceImpulse control disorders (ICDs) are frequent and particularly distressing neuropsychiatric symptoms in patients with Parkinson's disease, which are related to impaired behavioural inhibition. Multiple PET imaging studies indicate that striatal dopaminergic abnormalities contribute to hyperdopaminergic functioning in Parkinson's disease patients with ICD (PDICD+) and to the dysregulation of the limbic fronto-striatal networks, which are critical for reward-related decision impulsivity. However, the serotonergic system is central to response inhibition and plays a critical role in neuropsychiatric symptoms in PD, but its role remains undetermined in PDICD. We hypothesized that PDICD+ patients exhibit serotonergic dysfunction within the cortico-striato-pallido-thalamic circuits involved in the inhibitory control of behaviour and decided to investigate the pre- and postsynaptic serotonergic innervation using two highly specific PET tracers for the serotonin transporter (SERT) using 11C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (11C-DASB) and the 5-HT2A receptor using 18F-altanserin. In this prospective, case-control, double-tracer PET study, we recruited 15 PDICD+ patients, 15 PDICD- patients and 15 healthy controls, matched for age and sex, and compared the availability of 11C-DASB and 18F-altanserin using permutation-based analysis. PDICD+ patients had one (n = 9) or multiple ICDs (n = 6), consisting of hypersexuality (n = 8), compulsive eating (n = 6), compulsive shopping (n = 5) and pathological gambling (n = 4), and were characterized by greater choice impulsivity (impaired delay discounting for monetary rewards) and greater urgency with more severe depressive and anxious symptoms. We demonstrate that PDICD+ patients had greater 11C-DASB binding in the posterior putamen and pallidum in comparison to PDICD- patients, corresponding to relatively preserved presynaptic SERT availability within the subcortical sensorimotor network involved in response inhibition. In addition, cortical 18F-altanserin binding was greater in PDICD+ patients in the bilateral supplementary motor area, precentral gyrus and right dorsolateral prefrontal cortex, involving the sensorimotor and associative networks which regulate behavioural inhibition. Furthermore, we show that pre- and postsynaptic serotonergic dysfunction subserving action versus decision impulsivity in patients with Parkinson's disease specifically followed the distinctive functional organization of the sensorimotor and associative fronto-striatal networks. Altogether, we demonstrate that serotonergic dysfunction related to ICDs in Parkinson's disease specifically involve the sensorimotor and associative cortico-striato-pallido-thalamic circuits involved in inhibitory control. Thus, serotonergic dysfunction contributes to the mechanisms related to the vulnerability and development of ICDs in patients with Parkinson's disease, beyond the known dopaminergic abnormalities in the limbic fronto-striatal circuit
Leveraging Latent Space and Radiomics for Multi-Label Classification of Chest CT Scans
No full textInternational audienceIn this article, we propose two approaches for multi-label diagnosis from chest CT images. The first, called Seg2Clf, leverages the latent space of the encoder from a pre-trained segmentation model to extract discriminative representations for classification. The second approach relies on the extraction and integration of clinical radiomic features, allowing prediction refinement using a k-NN classifier. These two complementary methods are part of a broader strategy aimed at developing automated systems capable of simultaneously identifying multiple thoracic pathologies with improved accuracy.Dans cet article, nous proposons deux approches pour le diagnostic multi-label à partir d'images scanner thoraciques (CT). La première, nommée Seg2Clf, exploite l'espace latent de l'encodeur d'un modèle de segmentation pré-entraîné afin d'extraire des représentations discriminantes pour la classification. La seconde approche s'appuie sur l'extraction et l'intégration de caractéristiques radiomiques cliniques, permettant d'affiner les prédictions à l'aide d'un classificateur k-NN. Ces deux méthodes, complémentaires, s'inscrivent dans une stratégie globale visant à développer des systèmes automatisés capables d'identifier simultanément plusieurs pathologies thoraciques avec une meilleure précision
Associations between nocturnal autonomic activity in infancy and later neurocognitive development: the AuBE cohort study
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Cloxacillin versus cefazolin for meticillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): a prospective, open-label, multicentre, non-inferiority, randomised clinical trial
No full textInternational audienceBACKGROUND: Although widely used, cefazolin efficacy for the treatment of meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia has not thus far been investigated in a clinical trial. In this study, we aimed to compare the efficacy and safety of cefazolin with that of cloxacillin in patients with MSSA bacteraemia. METHODS: We conducted an open-label, non-inferiority, randomised clinical trial in 21 university and non-university hospitals in France in adults (aged ≥18 years) with MSSA bacteraemia, without intravascular implant or suspicion of CNS infection. Participants were randomly assigned (1:1) to receive intravenously cefazolin (25-50 mg/kg every 8 h) or cloxacillin (25-50 mg/kg every 4-6 h) for the first 7 days of therapy using computer-generated blocks of various sizes and stratification on vascular-access associated bacteraemia and centre. Subsequent treatment was left to the choice of the investigator (total duration ≥14 days). The primary endpoint was a composite of sterile blood cultures at day 3 (day 5 for endocarditis) without relapse of bacteraemia, survival, and clinical success at day 90, and was assessed in the intention-to-treat population. A non-inferiority margin of 12% was chosen. This trial is registered on ClinicalTrials.gov (NCT03248063) and is complete. FINDINGS: Between Sept 5, 2018, and Nov 16, 2023, 315 participants were enrolled and assigned to cefazolin (n=158) or cloxacillin (n=157); 12 participants were excluded from analysis in the cefazolin group, and 11 in the cloxacillin group (final population of 146 in each group). Mean age was 62·7 years (SD 16·4), 215 (74%) participants were male, and race or ethnicity data were not collected. Median Pitt score was 0 (IQR 0-0). The primary endpoint was met in 109 (75%) of 146 participants in the cefazolin group versus 108 (74%) of 146 participants in the cloxacillin group (treatment difference -1%; 95% CI -11 to 9; p=0·012). At the end of study treatment, 22 (15%) of 146 participants assigned to cefazolin and 40 (27%) of 146 participants assigned to cloxacillin had had a serious adverse event (p=0·010). Acute kidney injury occurred more frequently in participants assigned to cloxacillin (15 [12%] of 128) than in those assigned to cefazolin (one [1%] of 134; p=0·0002). INTERPRETATION: Cefazolin constitutes an alternative to cloxacillin for the treatment of MSSA bacteraemia, offering non-inferior clinical efficacy and potentially enhanced tolerability. FUNDING: French Ministry of Health