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Ultrafast dynamics of a spin-polarized electron plasma with magnetic ions
No full textInternational audienceWe construct a mean-field model that describes the nonlinear dynamics of a spin-polarized electron gas interacting with fixed, positively-charged ions possessing a magnetic moment that evolves in time. The mobile electrons are modeled by a four-component distribution function in the two-dimensional phase space (x, v), obeying a Vlasov-Poisson set of equations. The ions are modeled by a Landau-Lifshitz equation for their spin density, which contains ion-ion and electron-ion magnetic exchange terms. We perform a linear response study of the coupled Vlasov-Poisson-Landau-Lifshitz (VPLL) equations for the case of a Maxwell-Boltzmann equilibrium, focussing in particular on the spin dispersion relation. Condition of stability or instability for the spin modes are identified, which depend essentially on the electron spin polarization rate η and the electron-ion magnetic coupling constant K. We also develop an Eulerian grid-based computational code for the fully nonlinear VPLL equations, based on the geometric Hamiltonian method recently developed in [15]. This technique allows us to achieve great accuracy for the conserved quantities, such as the modulus of the ion spin vector and the total energy. Numerical tests in the linear regime are in accordance with the estimations of the linear response theory. For two-stream equilibria, we study the interplay of instabilities occurring in both the charge and the spin sectors. The set of parameters used in the simulations, with densities close to those of solids (≈ 10^{29} m^{-3} ) and temperatures of the order of 10 eV, may be relevant to the warm dense matter regime appearing in some inertial fusion experiments
Long-Term Efficacy and Safety of Rituximab in Patients With Pemphigus Foliaceus Compared With Pemphigus Vulgaris
No full textInternational audienceNo abstract availabl
Differentiating cerebral amyloid angiopathy from Alzheimer disease using dual amyloid and Tau Positron Emission Tomography
No full textInternational audienceBackground and Purpose.Although amyloid PET provides a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity relative to incipient Alzheimer's disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce the overlap by selecting "pure CAA" (i.e., fulfilling the criteria for probable CAA but without tau-PET AD signature) and "pure AD" (i.e., positive amyloid PET and presence of tau-PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to whole cortex (WC) would be higher in pure CAA, and may serve as a specific diagnostic marker.Methods. Patients fulfilling the above criteria were identified. In addition to the occipital ROI, we also assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as absolute SUVR and ROI/WC ratio. Diagnostic utility of amyloid PET was assessed using Youden index cutoff.Results. 18 AD and 42 CAA patients with comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.</div
Glycolytic activity following anti‐CD19 CAR‐T cell infusion in non‐Hodgkin lymphoma
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The RaDiCo information system for rare disease cohorts
No full textInternational audienceAbstract Background Rare diseases (RDs) clinical care and research face several challenges. Patients are dispersed over large geographic areas, their number per disease is limited, just like the number of researchers involved. Current databases as well as biological collections, when existing, are generally local, of modest size, incomplete, of uneven quality, heterogeneous in format and content, and rarely accessible or standardised to support interoperability. Most disease phenotypes are complex corresponding to multi-systemic conditions, with insufficient interdisciplinary cooperation. Thus emerged the need to generate, within a coordinated, mutualised, secure and interoperable framework, high-quality data from national or international RD cohorts, based on deep phenotyping, including molecular analysis data, notably genotypic. The RaDiCo program objective was to create, under the umbrella of Inserm, a national operational platform dedicated to the development of RD e-cohorts. Its Information System (IS) is presented here. Material and methods Constructed on the cloud computing principle, the RaDiCo platform was designed to promote mutualization and factorization of processes and services, for both clinical epidemiology support and IS. RaDiCo IS is based on an interoperability framework combining a unique RD identifier, data standardisation, FAIR principles, data exchange flows/processes and data security principles compliant with the European GDPR. Results RaDiCo IS favours a secure, open-source web application in order to implement and manage online databases and give patients themselves the opportunity to collect their data. It ensures a continuous monitoring of data quality and consistency over time. RaDiCo IS proved to be efficient, currently hosting 13 e-cohorts, covering 67 distinct RDs. As of April 2024, 8063 patients were recruited from 180 specialised RD sites spread across the national territory. Discussion The RaDiCo operational platform is equivalent to a national infrastructure. Its IS enables RD e-cohorts to be developed on a shared platform with no limit on size or number. Compliant with the GDPR, it is compatible with the French National Health Data Hub and can be extended to the RDs European Reference Networks (ERNs). Conclusion RaDiCo provides a robust IS, compatible with the French Data Hub and RDs ERNs, integrated on a RD platform that enables e-cohorts creation, monitoring and analysis
A phase 2 open-label pilot study of Remimazolam for sedation in critically ill patients
No full textInternational audienceIntroduction: Remimazolam is a novel benzodiazepine with an ultra-short half-life. It is a potentially interesting alternative for sedation in the Intensive Care Unit, but there is limited data regarding its use in critically ill patients.Methods: Phase 2, investigator-initiated, single-center, non-randomized, open-label study. Patients with an expected duration of sedation ≥ 24 h were eligible and received a maximum 48-h infusion of Remimazolam, with a dose ranging from 0.1 to 1 mg/min. The primary endpoint was a composite of the ability to reach a targeted sedation level without the use of another hypnotic drug and hemodynamic stability (no drop in mean arterial pressure ≤ 65 mmHg and no increase in norepinephrine dose ≥ 50% for more than 1 h), during the first 8 h after start. Secondary endpoints included the monitoring of Adverse Events (AE) and pharmacokinetics.Results: 30 patients were included with a median age of 60 [51-70] years, a SAPS II 38 [30-46], and a mortality rate of 23.3%. Fourteen (46.7%) patients met the primary endpoint. Ten (33.3%) patients received Remimazolam for 48 h and 4 (13.3%) patients received the highest dose. 54 AEs were reported in 23 patients and 11 were classified as Serious AEs in 8 patients. Ten AEs were related to Remimazolam. The pharmacokinetics analysis showed steady plasma levels throughout the infusion and rapid elimination after dosing discontinuation.Discussion: Remimazolam could be useful for sedation in the ICU but deserves further investigation before routine use.Trial registration: NCT04611425. Registered 2 November 2020
Impact of COVID-19 pandemic on childhood cancer incidence and stage in France – A national registry-based study
No full textInternational audienceCOVID-19 pandemic has considerably affected access to healthcare resources with global decline in cancer care activities in 2020. This national study aimed to assess a possible impact of the pandemic on the management of pediatric cancer cases. Methods: The study was based on the French National Childhood Cancer Registry and included all cases of cancer under 18 years of age diagnosed between January 1, 2016 and December 31, 2020. We estimated incidence rates, the proportion of advanced/metastatic stages (Toronto Pediatric Cancer Stage Guidelines) and the distribution of treatment initiation time during the 2020 pandemic period compared to the 2016–2019 reference period. Results: Age-standardized incidence rates of overall pediatric cancer were similar in 2020 (161.4 cases per million person-years; 2250 cases) and in 2016–2019 (162.4 cases per million person-years; 9208 cases). They were also similar by sex, age group, region, and cancer type. We did not observe any significant differences in stage at diagnosis or median time to treatment. Conclusion: Our nationwide population-based study suggests that pediatric cancer management was not substantially altered in 2020, despite the challenges induced by the COVID-19 pandemic and associated lockdown
Intra-arterial hepatic chemotherapy in metastatic colorectal cancer: differences between oxaliplatin-naive versus oxaliplatin-pretreated patients
No full textInternational audienceBackground: Oxaliplatin-based hepatic arterial infusions (HAI) combined with intravenous therapy is a therapeutic option for colorectal cancer with liver-only metastasis, notably in the palliative setting, either initially or after failure of systemic chemotherapy. Our study aimed to assess efficacy and tolerance between oxaliplatin-naive patients and oxaliplatin-pretreated patients. Methods: Between 2008 and 2022, single-center consecutive patients presenting with liver metastasis secondary to colorectal cancer who received at least one cycle of HAI-oxaliplatin combined with systemic therapy were included. Results: The oxaliplatin-naive arm included 63 patients (median age 58 years) and the pretreated arm included 244 patients (median age 53 years). Patient characteristics were well balanced between the groups. All patients in the oxaliplatin-naive arm received HAI-oxaliplatin while 13% of the pretreated patients received HAI-FOLFIRINOX. After a median follow-up of 36 months, median progression-free survival was 14 months in the oxaliplatin-naive group (range 11.8-24 months) and 10.1 months in the pretreated group (range 9.4-12.5 months) (P ¼ 0.016). The objective response rate was 66.7% and the disease control rate was 79.4% in the oxaliplatin-naive group, versus 32.4% and 77.5% (P < 0.001) in the pretreated group. Grade 3-4 toxicities were comparable between the two groups, including neuropathy. Secondary resection/ablation rate was 22.2% in oxaliplatin-naive patients and 17.6% in pretreated patients. Conclusion: Oxaliplatin use as an intra-arterial hepatic infusion is feasible and efficient after previous systemic oxaliplatin; it showed significant response rates without increased toxicities. It can provide alternative treatments and spare late-setting drugs such as regorafenib and tipiraciletrifluridine for a further palliative intent treatment.</div
Genetics of Catatonia: a systematic review of case reports and a gene pathway analysis
No full textInternational audienceNo abstract availabl
Progression of Kidney Fibrosis after Sepsis: The Underestimated Role of Resident Macrophages and Recruited Monocytes
No full textInternational audienceSepsis is a life-threatening condition affecting each year an estimated 49 million people and causing 11 million deaths. Short-term mortality of sepsis was substantially reduced during the past decades and is still improving. Besides its short-term lethality, awareness regarding long-term consequences of sepsis is rising. Among all organs affected during sepsis, the kidney is the most vulnerable. Up to 40% of patients suffering from sepsis develop acute kidney injury (AKI), and sepsis is the leading cause of AKI among critically ills. Half of patients will recover from AKI during their stay; however, several studies have pointed out that those patients were at increased risk for the development of subsequent chronic kidney disease (CKD). In patients suffering from transient AKI, a second injury was found to hasten renal fibrogenesis. Taken together those findings challenge the concept of ad integrum recovery and strongly suggest maladaptive repair AKI, together with profound and durable alterations at intra-organ level. Factors driving AKI to CKD after sepsis are poorly understood and could be of multiple origins. Kidney macrophages have pleiotropic roles in health and disease. Following sepsis, a proportion of kidney macrophages undergoes pyroptosis in an “altruist” maneuver to recruit inflammatory cells. Empty niches are later colonized by circulating monocyte arising from bone marrow in a process called emergency myelopoiesis but also by expansion of resident cells. The role of monocytes and macrophages in the acute phase of sepsis is well described, however, their role in the resolution of inflammation is just beginning to be understood. In the present review, we will discuss the fate of kidney resident macrophages and recruited monocytes in septic AKI. We will review the evidence linking changes in the immune landscape and maladaptive repair after sepsis. Finally, we will consider how targeting macrophage recruitment and polarization might influence sepsis long-term consequences