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Prevention of extubation failure in neurocritical care patients with residual disorder of consciousness: the Brain-Injured Patients Extubation Readiness (BIPER) study protocol for a stepped-wedge cluster-randomised controlled trial
No full textInternational audienceIntroduction In the intensive care unit (ICU), brain-injured patients are frequently exposed to mechanical ventilation to protect the brain and preserve physiology. After intracranial pressure control and sedation withdrawal, this population is prone to residual disorder of consciousness and altered neurological control of respiratory drive, cough and airway protection. Consequently, extubation failure is more frequent than in general ICU patients, and there is no clear evidence-based clinical trigger for extubation. Different risk factors for extubation failure were described in observational trials, and clinical scores were constructed to detect patients at higher risk of extubation failure. Nevertheless, none of these scores were prospectively tested as interventional tools to prevent extubation failure. The Brain-Injured Patients Extubation Readiness (BIPER) study is an ongoing multicentre stepped-wedge cluster-randomised controlled trial aiming to test one of these scores as an intervention protocol to decrease extubation failure in neurocritical care patients with residual disorder of consciousness. Methods and analysis Trial design: Stepped-wedge cluster-randomised controlled trial with five groups of three to six clusters (20 ICUs). Groups of clusters are randomised to five possible sequences of nine periods with crossing from a control condition period (usual care for extubation) to an intervention condition period (BIPER-guided extubation protocol), separated by a 3-month transition period. Participants: Participants are clinically stable brain-injured patients (18–75 years old), requiring more than 48 hours of invasive mechanical ventilation with residual disorder of consciousness after sedation withdrawal, and who achieved a spontaneous breathing trial. Interventions: The control condition consists of extubation based on usual care and local practice. The intervention condition consists of extubation triggered by a clinical score evaluating deglutition, gag reflex, cough and visual tracking (Coma Recovery Scale-Revised Visual Scale). Objective: To determine whether adoption of an extubation protocol based on a clinical score can lessen extubation failure compared with usual care in brain-injured patients with residual disorder of consciousness. Outcome: The primary outcome measure is extubation failure, defined within 5 days following extubation. The key secondary outcome measure is time to effective extubation. Randomisation: Clusters are allocated to sequence of treatments using random blocks randomisation. The constitution of groups of clusters was stratified according to planned recruitment of each centre. Blinding: Investigators and outcome assessors are not blinded to condition allocation. Number of participants: 660 patients (220 in the control condition and 440 in the intervention condition). Ethics and dissemination The BIPER trial was approved by an independent ethics committee. The study began on 9 February 2020, and 571 participants are now included. Results will be published in an international peer-reviewed medical journal. Trial registration number NCT04080440
Optimizing Sample Size and Statistical Methods for Probabilistic Sweet Spot Mapping in Deep Brain Stimulation
No full textSession: Neural stimulation 1 (Oral Session).International audienceDeep Brain Stimulation (DBS) for movement disorders can greatly benefit from the insights provided by probabilistic mapping. This consists in the application of statistical approaches to stimulation data of multiple patients. Such analysis is influenced by the input data and chosen statistical method, hindering the generalizability of the obtained results. This study aims at determining the minimum sample size yielding stable results, and the statistical approach providing higher results consistency. Intra-operative stimulation test data of 36 patients who underwent DBS surgery for Parkinson’s Disease (PD), were used to compute Probabilistic Sweet Spots (PSS). The PSS were calculated with sample sizes ranging from 4 to 36 (steps of 2) using Bayesian t-test, Wilcoxon test with False Discovery Rate correction and Wilcoxon test with nonparametric permutations correction. Calculations were repeated 10 times. Obtained PSS were compared in terms of size and position variability across sample sizes and between statistical methods. Only the PSS computed with the Bayesian t-test reached stability in all the three chosen metrics. Stability in size and centroid location was reached from a sample size of 14 patients, while the covered volume (Dice coefficient) stabilized from a sample size of 18 patients. The Bayesian t-test also provided higher results consistency with respect to the other approaches. The composition of the dataset in cohorts with <20 patients has a greater influence on the extent and location of computed PSS. Moreover, the Bayesian t-test demonstrated the highest suitability to extrapolate results from analyses involving small sample sizes
Napping and memory consolidation in early childhood: A systematic review and meta-analysis
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Yeast fungaemia among injection drug users in France (2012–2022): a cross-sectional observational study
No full textFrench Mycoses Study Group : Taieb Chouaki,Marc Pihet,Anne-Pauline Bellanger,Magalie Demar,Nicole Desbois-Nogard,Muriel Nicolas,Marie-Fleur Durieux,Milène Sasso,Estelle Perraud-Cateau,Jean-Pierre Gangneux,Caroline Mahinc,Sophie Cassaing,Adelaide Chesnay,Guillaume Desoubeaux,André Paugam,Elisabeth Chachaty,Marie-Elisabteth Bougnoux,Lilia Merabet,Patricia Mariani,Maité MicaeloInternational audienceBackgroundIntravenous injection drug use (IVDU) is an established but infrequent risk factor for yeast fungaemia. We aimed to identify features and outcomes of yeast fungaemia associated with IVDU in a nationwide surveillance network in France.MethodsWe prospectively included episodes of yeast fungaemia in adults between 2012 and 2022. Episodes with any history of IVDU were considered IVDU-associated. We compared clinical characteristics, infecting species, antifungal treatments, and 90-day mortality between groups. We used Fisher's exact test for categorical variables and the Kruskal–Wallis test for continuous variables.FindingsWe recorded 9549 episodes of yeast fungaemia among 9132 adults. Among these, 183 (1·9%) were IVDU-associated. Compared with non-IVDU, individuals with IVDU-associated fungaemia were younger and less likely to have a history of malignancy (13·8%, 20/145 vs. 49·5%, 4447/8987, p < 0·0001) or recent surgery (24·3%, 34/140 vs. 37·3%, 3261/8,733, p = 0·0014), and more likely to have deep-seated infections (14·5%, 21/145 vs. 3·4%, 307/8987, p < 0·0001). IVDU cases less often involved Candida albicans (30·1%, 55/183 vs. 47·6%, 4458/9366, p < 0·0001) and more often involved mixed-species infections (13·1%, 24/183 vs. 4·3%, 402/9366), p < 0·0001. Meyerozyma guilliermondii and Wickerhamomyces anomalus were overrepresented among IVDU cases (6·0%, 11/183 vs. 0·5%, 48/9366, p < 0·0001 and 5·5%, 10/183 vs. 0·05%, 5/9366, p < 0·0001, respectively). The crude 90-day case-fatality ratio was 20·7% (95% CI: 13·7%–29·2%) in the IVDU group versus 48·4% (95% CI: 47·3–49·5%) for non-IVDU.InterpretationIVDU-associated yeast fungaemia presents distinct clinical and microbiological characteristics, highlighting the need for tailored diagnosis and management
Response surface methodology for predicting optimal conditions in very low-dose chest CT imaging
No full textInternational audienceObjective: Dose reduction techniques, such as new reconstruction algorithms and automated exposure control systems vary with manufacturer and scanner models, complicating the optimization and standardization procedures. We investigated the feasibility of using the design of experiments in CT protocols optimization. Materials & Methods: A Doehlert matrix was used to define the experiments to carry out. Measurements were conducted on a 128-slice CT scanner using an anthropomorphic chest phantom with a 5 mm diameter lesion that has a HU of -800. CT images were reconstructed using iterative (ASIR-V) and deep learning-based reconstruction techniques at low (DLIR-L) and high (DLIR-H) strengths. Lesion detectability was assessed using two self-supervised learning-based model observers and six human observers. Second-order polynomial functions have been established to model the combined effect of noise index (NI) and percentage of ASIR-V on dose and model observers' performances. The analysis of agreement between model and human observers was performed using correlation coefficients and Bland-Altman test. Results: The optimal conditions predicted by this method were NI = 64, % ASIR-V = 60 and DLIR-H reconstruction. They were found in good agreement with the experimental results obtained by the average human observer, as showed by the Bland-Altman plot with a mean absolute difference of -0.01 ± 3.16. Compared to 60 % ASIR-V, these results suggested an approximately 64 % dose reduction potential for DLIR-H without compromising lesion detection.Conclusion:The proposed method can predict the optimal conditions that ensure diagnostic quality of low-dose chest CT examinations, while minimizing the number of experiments to carry out
Gut microbial dysbiosis associated to diarrheic irritable bowel syndrome can be efficiently simulated in the Mucosal ARtificial COLon (M-ARCOL)
No full textInternational audienceIrritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, with diarrhea-predominant IBS (IBS-D) as the most frequent subtype. The implication of gut microbiota in the disease's etiology is not fully understood. In vitro gut systems can offer a great alternative to in vivo assays in preclinical studies, but no model reproducing IBS-related dysbiotic microbiota has been developed. Thanks to a large literature review, a new Mucosal ARtifical COLon (M-ARCOL) adapted to IBS-D physicochemical and nutritional conditions was set-up. To validate the model and further exploit its potential in a mechanistic study, in vitro fermentations were performed using bioreactors inoculated with stools from healthy individuals (n=4) or IBS-D patients (n=4), when the M-ARCOL was set-up under healthy or IBS-D conditions. Setting IBS-D parameters in M-ARCOL inoculated with IBS-D stools maintained the key microbial features associated to the disease in vivo, validating the new system. In particular, compared to the healthy control, the IBS-D model was characterized by a decreased bacterial diversity, together with a lower abundance of Rikenellaceae and Prevotellaceae, but a higher level of Proteobacteria and Akkermansiaceae. Of interest, applying IBS-D parameters to healthy stools was not sufficient to trigger IBS-D dysbiosis and applying healthy parameters to IBS-D stools was not enough to restore microbial balance. This validated IBS-D colonic model can be used as a robust in vitro platform for studies focusing on gut microbes in the absence of the host, as well as for testing food and microbiota-related interventions aimed at personalized restoration of gut microbiota eubiosis
High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis The D-Lay MS Randomized Clinical Trial
No full textInternational audienceImportance Vitamin D deficiency is a risk factor for multiple sclerosis (MS) and is associated with the risk of disease activity, but data on the benefits of supplementation are conflicting. Objective To evaluate the efficacy of high-dose cholecalciferol as monotherapy in reducing disease activity in patients with clinically isolated syndrome (CIS) typical for MS. Design, Setting, and Participants The D-Lay MS trial was a parallel, double-blind, randomized placebo-controlled clinical trial in 36 MS centers in France. Patients were enrolled from July 2013 to December 2020 (final follow-up on January 18, 2023). Untreated patients with CIS aged 18 to 55 years with CIS duration less than 90 days, serum vitamin D concentration less than 100 nmol/L, and diagnostic magnetic resonance imaging (MRI) meeting 2010 criteria for dissemination in space or 2 or more lesions and presence of oligoclonal bands were recruited. Intervention Patients were randomized 1:1 to receive oral cholecalciferol 100 000 IU (n = 163) or placebo (n = 153) every 2 weeks for 24 months. Main Outcomes and Measures The primary outcome measure was disease activity, defined as occurrence of a relapse and/or MRI activity (new and/or contrast-enhancing lesions) over 24 months of follow-up, also analyzed as separate secondary outcomes. Results Of the 316 participants enrolled and randomized (median [IQR] age, 34 [28-42] years; 70% women), the primary analysis included 303 patients (95.9%) who took at least 1 dose of the study drug and 288 (91.1%) ultimately completed the 24-month trial. Disease activity was observed in 94 patients (60.3%) in the vitamin D group and 109 patients (74.1%) in the placebo group (hazard ratio [HR], 0.66 [95% CI, 0.50-0.87]; P = .004), and median time to disease activity was longer in the vitamin D group (432 vs 224 days; log-rank P = .003). All 3 secondary MRI outcomes reported significant differences favoring the vitamin D group vs the placebo group: MRI activity (89 patients [57.1%] vs 96 patients [65.3%]; HR, 0.71 [95% CI, 0.53-0.95]; P = .02), new lesions (72 patients [46.2%] vs 87 patients [59.2%]; HR, 0.61 [95% CI, 0.44-0.84]; P = .003), and contrast-enhancing lesions (29 patients [18.6%] vs 50 patients [34.0%]; HR, 0.47 [95% CI, 0.30-0.75]; P = .001). All 10 secondary clinical outcomes showed no significant difference, including relapse, which occurred in 28 patients (17.9%) in the vitamin D group vs 32 (21.8%) in the placebo group (HR, 0.69 [95% CI, 0.42-1.16]; P = .16). Results were similar in a subset of 247 patients meeting updated 2017 diagnostic criteria for relapsing-remitting MS at treatment initiation. Severe adverse events occurred in 17 patients in the vitamin D group and 13 in the placebo group, none of which were related to cholecalciferol. Conclusions and Relevance Oral cholecalciferol 100 000 IU every 2 weeks significantly reduced disease activity in CIS and early relapsing-remitting MS. These results warrant further investigation, including the potential role of pulse high-dose vitamin D as add-on therapy. Trial Registration ClinicalTrials.gov Identifier: NCT0181716
Primary mediastinal B-cell lymphoma (PMBCL): The LYSA pragmatic guidelines
No full textInternational audiencePrimary mediastinal B-cell lymphoma (PMBCL) is a distinct subtype of large B-cell lymphoma with unique clinical, histopathological, and molecular characteristics. Despite its aggressive nature, PMBCL has a high cure rate when managed appropriately. Advances in the understanding of PMBCL biological characteristics, coupled with improvements in diagnostic tools and therapeutic approaches, have significantly improved patient outcomes in recent years. In this article, we present a set of pragmatic guidelines developed by the Lymphoma Study Association (LYSA) for the management of PMBCL. These guidelines address key aspects of diagnosis, staging, response evaluation, and treatment, integrating the latest evidence from clinical trials, expert consensus, and real-world practice. The aim of the guidelines is to provide clinicians with a clear, practical framework to optimize care for patients with PMBCL, ensuring that the best available evidence is translated into clinical practice
DOP087 Characterization of a European population with recently diagnosed Crohn’s Disease: results from the prospective Crohn´s Disease Cohort (CROCO) Study
No full textInternational audienceBackground Crohn’s disease (CD) is a chronic and progressive condition with a growing global prevalence, leading to potential bowel damage and disability. Data on the clinical presentation, outcomes, and treatment options in newly diagnosed CD patients in Europe in the current era are essential to guide physicians. The aim is describe the clinical characteristics of a contemporary European cohort of recently diagnosed CD patients. Methods The Crohn's Disease Cohort (CROCO) is an ongoing, multicenter, European prospective study of CD patients diagnosed within the last 12 months, aimed at tracking bowel damage progression and disability. This report presents the baseline characteristics at study inclusion. Results From August 2021 to October 2024, 399 patients (56% male, 46% current or former smokers) with a median age at diagnosis of 33.7 years (IQR 24.6; 49.2) were recruited across 18 centers. The median delay between symptom onset and diagnosis was 6.2 months (IQR 2; 15.4), and the median disease duration at inclusion was 3.8 months (IQR 1.6; 7.4). Ileal involvement (L1/L3) was reported in 85% of patients. Overall, 15% had perianal disease and 28% had extraintestinal manifestations, predominantly arthritis/arthralgia. Complicated disease behavior was observed in 32% of patients at diagnosis (stricturing: 17%; penetrating: 15%); 6% had undergone intestinal surgery, and 3% perianal surgery from diagnosis to inclusion. CD-related hospitalizations were reported by 22% of patients. Regarding treatments, 51% received steroids (28% systemic steroids), 17% 5-ASA, 1% immunosuppressants monotherapy, and 44% initiated biological therapy (168 anti-TNF, 8 anti-IL 12/23, and 6 anti-integrin, representing 42%, 2% and 2% of the cohort, respectively). A total of 31% were managed with a combination of biologic and immunosuppressant therapies. Disability assessment showed that 48% of patients reported no disability, 24% mild disability, and 28% moderate to severe disability. Conclusion In this prospective European cohort of newly diagnosed CD patients, nearly one-third had a complicated disease phenotype and moderate to severe disability, despite a relatively short diagnostic delay. While steroid use remains common, early initiation of biological therapy in 44% of patients reflects a shift in CD management strategies
High-throughput screening to identify endocrine disruptors: Contribution of low-resolution tandem MS and high-resolution MS
No full textInternational audienceTelomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of telomere shortening and replicative senescence in Saccharomyces cerevisiae which is quantitatively calibrated and validated using data of telomerase-deficient single cells. Simulations of yeast populations, where cells with varying proliferation capacities compete against each other, show that the distribution of telomere lengths of the initial population shapes population growth, especially through the distribution of cells’ shortest telomere lengths. We also quantified how factors influencing cell viability independently of telomeres can impact senescence rates. Overall, we demonstrate a temporal evolution in the composition of senescent cell populations—from a state directly linked to critically short telomeres to a state where senescence onset becomes stochastic. This population structure may promote genome instability and facilitate senescence escape