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Transcranial Doppler to guide early discharge after mild traumatic brain injury, the TRUST trial: study protocol for an open-label multisite noninferiority randomized controlled trial
No full textInternational audienceBackground: After mild traumatic brain injury (TBI), discharge from the emergency department (ED) relies on clinical examination and brain imaging, but triaging of these patients can be challenging in specific situations. Transcranial Doppler (TCD) after mild TBI may rule out early neurologic worsening. We hypothesize that patients with mild TBI and normal TCD can be safely discharged home immediately after the ED.Methods: This is a prospective, open-label, multisite, randomized controlled noninferiority trial. Eligible patients are mild TBI patients (Glasgow Coma Scale, GCS, 13-15 on admission) with minor lesions on brain CT scan or normal CT scan but one of the following risk factors: (1) GCS = 14 after CT scan; (2) alcoholic intoxication, (3) ongoing treatment with anticoagulants or anti-platelet therapy; (4) persisting nausea, vomiting, and/or headaches; or (5) early initial CT scan (< 4 h after TBI). Patients randomized in the intervention group have TCD within 12 h after TBI and can be immediately discharged from the ED if TCD is normal (diastolic flow velocity higher than 25 cm/s and pulsatility index lower than 1.25). Discharge of patients in the control group relies on clinical examination and brain imaging only. The primary outcome is the 3-month neurological outcome measured with the Extended Glasgow Outcome Scale (GOS-E). Secondary outcomes are the GOS-E at 1 month, the QOLIBRI (Quality of life after TBI) and EQ-5D-5L questionnaires at 1 month and 3 months after TBI, the Rivermead Post-Concussion Symptoms questionnaire at 1 month and 3 months after TBI, mortality within the first 3 months, the number of cerebral CT scans, length of stay in hospital, the number of thromboembolic events or diagnosed nosocomial infections, and the number of patients re-admitted to hospital in relation with the initial TBI. Inclusions have started in February 2020 and are expected to be complete by June 2025.Discussion: Transcranial Doppler in mild TBI patients may help immediate discharge from the ED after CT scanning
Compartmentalized cytotoxic CD4 + T cell responses in anti-Yo paraneoplastic cerebellar degeneration
No full textInternational audienceParaneoplastic cerebellar degeneration with anti-Yo antibodies (Yo-PCD) is a rare neurological disorder associated with breast and gynecological cancers. Although T cell–mediated immunity against Purkinje cell antigens CDR2/CDR2L has been implicated, the precise mechanisms remain undefined. Here, we applied single-cell RNA sequencing and paired T cell receptor profiling to cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) from six Yo-PCD patients and five ovarian cancer patients without paraneoplastic disease, with additional controls from individuals with multiple sclerosis or idiopathic intracranial hypertension. PBMCs from both cancer cohorts exhibited pro-inflammatory signatures. However, uniquely in Yo-PCD, antigen-presenting cells (APCs) and regulatory T cells showed reduced expression of tolerance-associated genes, including key components of the TGF-β pathway. Moreover, Yo-PCD APCs showed compartment-specific programs, with peripheral APCs enriched for MHC-I and inflammatory mediators, whereas CSF APCs upregulated MHC-II and interferon-stimulated genes. Yo-PCD CSF subclustering revealed no disease-specific expansion of CD8⁺ T cells. In contrast, CD4⁺ cytotoxic T cells were clonally expanded, spanned graded cytotoxic states, expressed central nervous system homing signatures, and overlapped with helper T cell clones, consistent with local reprogramming. Supporting their pathological relevance, CD4⁺ granzyme B⁺ T cells were identified in patient cerebellar tissue. Together, these findings define a dual-compartment immunopathology in Yo-PCD, highlighting CD4⁺ cytotoxic T cells as biomarkers and therapeutic targets
La nutrition parentérale perdialytique : théorie et application pratique
No full textInternational audienceProtein energy wasting is common in chronic kidney disease at the dialysis stage. It has an impact on morbidity and mortality, and must be diagnosed and treated as early as possible. Various strategies can be envisaged, including dietary counseling, prescription of Oral Nutritional Supplements or artificial nutrition (enteral or parenteral nutrition). Intradialytic parenteral nutrition (IDPN) involves administering parenteral nutrition during hemodialysis sessions to support a moderate food intake deficit. In this article, a group of nephrologists, dieticians and nutrition physician the indications, non-indications, administration and monitoring of IDPN. In particular, they analyze IDPN infusion rates in relation to the maximum metabolic capacities of the various nutrients
Dexmedetomidine to Reduce Vasopressor Resistance in Refractory Septic Shock: α2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS): A Double-Blind Randomized Controlled Pilot Trial
No full textInternational audienceOBJECTIVES: Increasing evidence has suggested the benefits of dexmedetomidine in patients with sepsis. Dexmedetomidine may increase vasopressor sensitivity, which may be of interest in the setting of refractory septic shock. The α2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS) pilot study aimed to evaluate the effect of dexmedetomidine on the vasopressor response in patients with refractory septic shock. DESIGN: This study was a multicenter, randomized, placebo-controlled, double-blind pilot trial. SETTING: The study was conducted in 5 ICUs in France. PATIENTS: Inclusion criteria were septic shock (Sepsis-3 definition) and norepinephrine requirement greater than or equal to 0.25 µg/kg/min (0.5 µg/kg/min of norepinephrine tartrate) with persistent circulatory failure (defined by lactate > 2 mmol/L, oliguria, or skin mottling) and invasive mechanical ventilation. INTERVENTIONS: The arterial pressure response to phenylephrine was measured before starting the treatment (0 hr), at 6 hours (primary outcome), and 12 hours. In the treatment arm, dexmedetomidine was given at a fixed dose of 1 µg/kg/hr. MEASUREMENTS AND MAIN RESULTS: Inclusions were stopped early because of higher mortality in the dexmedetomidine arm. Thirty-two patients of the 36 planned were included. Response to phenylephrine at 6 hours was lower in the dexmedetomidine group than in the placebo group (1.26 ± 0.23 vs. 1.45 ± 0.26; p = 0.048), although this difference was also observed at baseline ( p = 0.029). There were no significant differences between the groups in terms of cumulative norepinephrine dose, lactatemia, Sequential Organ Failure Assessment score, fluid balance, ventilation-free days, or occurrence of bradycardia. Mortality on day 3 was higher in the dexmedetomidine group than in the placebo group, with a difference that diminished and was no longer significant on 30 and 90 days. CONCLUSIONS: Patients in the dexmedetomidine arm had a significantly lower response to phenylephrine at all study times including baseline, which might have contributed to higher early mortality in the dexmedetomidine arm and preclude to conclude on dexmedetomidine efficacy in refractory septic shock. However, heart rate was not decreased in the dexmedetomidine arm.Trial registration: ClinicalTrials.gov NCT0395367
A European Survey to Identify Challenges in the Management of Metabolic Dysfunction‐Associated Steatotic Liver Disease
No full textInternational audienceBackground and Aims Metabolic dysfunction‐associated steatotic liver disease (MASLD) and its more severe subtype, metabolic dysfunction‐associated steatohepatitis (MASH), are highly prevalent and strongly associated with obesity and type 2 diabetes (T2D). This study sought to identify challenges to the diagnosis, treatment and management of people living with MASLD and MASH and understand the key barriers to adopting relevant clinical guidelines. Methods A real‐world, cross‐sectional study (BARRIERS‐MASLD) consisting of a quantitative survey and qualitative interviews of physicians in France, Germany, Italy, Spain and the United Kingdom was conducted from March to September 2023. Descriptive statistics were used for data analysis. Results A total of 626 physicians completed the survey; n = 10 from each country participated in the qualitative interviews. Physicians considered the presence of MASH to be highly impactful on how they treated people living with obesity (66%) and T2D (69%). Over one‐third (35%) of the respondents could not identify any MASH‐specific clinical guidelines issued by medical societies or associations top‐of‐mind, but overall awareness rose when prompted about country‐specific guidelines. Physicians said they would need evidence of success (48%) and clinical guidelines that address common MASLD comorbidities (38%) to increase their adoption. Conclusions This study found that lack of awareness around MASLD and MASH clinical guidelines and clearly established care pathways, particularly for addressing common comorbidities, was a key factor preventing physicians from optimising care for people living with MASH in Europe. This research highlights opportunities to improve education and training about clinical guidelines and care coordination
Prevalence of low bone mineral density in robotic-assisted TKA candidates: insights from quantitative CT analysis
No full textInternational audienceIntroduction: Osteoporosis is a prevalent and often underdiagnosed condition that significantly increases the risk of fragility fractures. Dual-energy X-ray absorptiometry (DXA) is the standard diagnostic tool; however, many patients remain unscreened. Preoperative computed tomography (CT) scans obtained for robotic-assisted total knee arthroplasty (TKA) planning present an opportunity for opportunistic osteoporosis screening without additional radiation exposure. Methods: A retrospective observational study was conducted on 637 patients (307 males, 330 females) who underwent robotic-assisted TKA between January 2023 and December 2024. Preoperative CT scans were analyzed using quantitative computed tomography (QCT) software to determine T-scores, Z-scores, and percentage of bone mineral density (BMD) relative to a young-adult reference. Patients were categorized as normal (T-score ≥ −1.0), osteopenic (−2.5 < T-score < −1.0), or osteoporotic (T-score ≤ −2.5). Results: Among 597 patients with available T-score data, 41.0% were classified as normal, 32.3% as osteopenic, and 26.6% as osteoporotic. Notably, 37.0% of female patients were osteoporotic compared to 15.3% of male patients. Bone density parameters declined progressively with age, with females over 80 years exhibiting a mean T-score of −2.53 and BMD at 68.25% of the young-adult reference. Discussion: Opportunistic screening using preoperative CT scans in robotic-assisted TKA patients reveals a high prevalence of undiagnosed low BMD, particularly among elderly women. Integrating QCT analysis into the preoperative workflow may facilitate early identification of at-risk individuals, informing surgical planning and enabling timely interventions to improve bone health
Early Start Denver Model effectiveness in young autistic children: a large multicentric randomised controlled trial in two European countries.
No full textInternational audienceBackground Evidence regarding early interventions based on the Naturalistic Developmental Behavioral Interventions framework, such as the Early Start Denver Model (ESDM), suggests efficacy for autistic children. However, the effectiveness of ESDM across diverse cultural contexts remains under-researched. Objective To assess the effectiveness of ESDM compared with treatment as usual (TAU) on overall development in young children with autism spectrum disorder (ASD). Method This parallel, randomised controlled trial, using a modified Zelen design, was conducted in five Child and Adolescent Mental Health Services in France and Belgium. A total of 180 children aged 19–36 months, who met autism criteria and were referred by community professionals, were randomly assigned to either receive 12-hour weekly ESDM+TAU or TAU alone. The primary outcome was the change in developmental quotient (DQ) on the Mullen Scale of Early Learning, assessed blindly from baseline to 24 months post randomisation. Findings From September 2015 to March 2019, 180 children were randomly assigned to either ESDM+TAU (n=61, girls=21.7%) or TAU alone (n=119, girls=15.4%). Three children dropped out immediately after randomisation. Compared with TAU alone, children in the ESDM+TAU group did not significantly improve global DQ (endpoint mean difference 3.82 (95% CI −1.25 to 8.89), p=0.14). Conclusions and clinical implications Our findings suggest that ESDM+TAU cannot be universally recommended for young children with ASD. Further research is required to evaluate the long-term effectiveness of ESDM and identify subgroups that may benefit more, thereby guiding optimal implementation strategies. Trial registration number NCT02608333
Particle-Based Framework for Continuous Fields of Coupled Phase Oscillators: Exploring Spontaneous Local Synchronization
No full textWe introduce a particle-based framework inspired by smoothed particle hydrodynamics (SPH) to simulate the dynamics of a continuous field of coupled phase oscillators. This methodology discretizes the spatial domain into particles and employs a smoothing kernel to model non-local interactions, enabling the exploration of how spatial heterogeneities and interaction ranges influence the synchronization and pattern formation of coupled phase oscillators. Notably, we observe the emergence of spatially localized synchronization clusters, providing evidence for spontaneous local synchronization in these systems. This local synchronization refers to the transition from an initially homogeneous state, where no preferred spatial organization exists, to one where structured synchronization patterns emerge due to local interactions. Our results advance the theoretical understanding of spatiotemporal synchronization and demonstrate the utility of SPH-inspired techniques for modeling complex, spatially distributed systems. These findings are particularly relevant to applications where spatial interactions drive collective dynamics, such as in neural systems, ecosystems, power grids, social models, chemical oscillators, and climate systems, as well as in condensed matter and collective phenomena involving synchronization
Shedding light on microsleep episodes for comprehensive sleepiness assessment: a narrative review
No full textInternational audienceExcessive daytime sleepiness is a consistent and common symptom in sleep medicine. It represents a major public health problem due to its association with significant impairments in quality of life, work productivity, and driving ability. Objective clinical tests for assessing excessive daytime sleepiness follow the universal American academy of sleep medicine scoring classification, which overlooks short intrusions of sleep during wake states, known as microsleep episodes. This narrative review provides a comprehensive summary of the existing literature concerning microsleep episodes, highlighting their significance and potential additional value in the context of sleepiness assessment. Moreover, due to the related attention lapses they cause, microsleep episodes may have significant implications for cognitive performance and road traffic accidents. These are discussed along with potential effective countermeasures. This review concludes by proposing an innovative framework for enriching excessive daytime sleepiness evaluation by integrating the assessment of microsleep episodes into routine clinical tests. Such an approach promises to provide valuable insights into the dynamics of sleepiness and could significantly enhance excessive daytime sleepiness assessment and management through personalized medicine