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OBJECTIVES: Anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitides (AAV) are rare conditions characterized by inflammatory cell infiltration in small blood vessels, leading to tissue necrosis. While most patients with AAV present antibodies against either myeloperoxidase (MPO) or proteinase 3 (PR3), rare cases of dual positivity for both antibodies (DP-ANCA) have been reported, and their impact on the clinical picture remains unclear. The goal of this study was to investigate the clinical implications, phenotypic profiles, and outcomes of patients with DP-ANCA. METHODS: A retrospective screening for DP-ANCA cases was conducted at Brest University Hospital's immunology laboratory (France), analyzing ANCA results from March 2013 to March 2022. Clinical, biological, imaging, and histological data were collected for each DP-ANCA case. Additionally, a comprehensive literature review on DP-ANCA was performed, combining an AI-based search using BIBOT software with a manual PUBMED database search. RESULTS: The report of our cases over the last 9 years and those from the literature yielded 103 described cases of patients with DP-ANCA. We identified four distinct phenotypic profiles: (i) idiopathic AAV (â¼30%), (ii) drug-induced AAV (â¼25%), (iii) autoimmune disease associated with a low risk of developing vasculitis (â¼20%), and (iv) immune-disrupting comorbidities (infections, cancers, etc) not associated with AAV (â¼25%). CONCLUSION: This analysis of over a hundred DP-ANCA cases suggests substantial diversity in clinical and immunopathological presentations. Approximatively 50% of DP-ANCA patients develop AAV, either as drug-induced or idiopathic forms, while the remaining 50%, characterized by pre-existing dysimmune conditions, demonstrates a remarkably low vasculitis risk. These findings underscore the complex nature of DP-ANCA, its variable impact on patient health, and the necessity for personalized diagnostic and management approaches in these cases.
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BACKGROUND: Admission to the hospital is a major risk factor for the development of venous thromboembolism (VTE). Whether thromboprophylaxis with low-molecular-weight heparin prevents symptomatic VTE in medically ill, hospitalized older adults remains debated. METHODS: In a prospective, randomized, placebo-controlled, double-blind, multicenter trial, older adults (>70 years of age) hospitalized for acute medical conditions were randomly assigned to receive 40 mg a day of low-molecular-weight heparin (enoxaparin) or placebo for 6 to 14 days. The primary efficacy outcome was the cumulative incidence of symptomatic VTE (distal or proximal deep vein thrombosis, fatal or nonfatal pulmonary embolism) at 30 days. The primary safety outcome was major bleeding. Secondary outcomes included efficacy and safety outcomes at 90 days. RESULTS: The trial was prematurely discontinued in September 2020, 5 years after enrollment began, because of drug supply issues. By the time of trial discontinuation, 2559 patients had been randomly assigned at 47 centers. Median age was 82 years and 60% of patients were female. In the intention-to-treat population, the primary efficacy outcome occurred in 22 out of 1278 (cumulative incidence, 1.8%) patients in the enoxaparin group and in 27 out of 1263 (cumulative incidence, 2.2%) patients in the placebo group (cumulative incidence difference, −0.4 percentage points; 95% confidence interval, −1.5 to 0.7), with no significant difference in time to VTE (P=0.46). The incidence of major bleeding was 0.9% in the enoxaparin group and 1.0% in the placebo group. At 90 days there were 14 symptomatic pulmonary emboli in the enoxaparin group and 25 in the placebo group; all 39 pulmonary embolism events resulted in hospital readmission and/or death, with 5 deaths from pulmonary embolism in the enoxaparin group and 11 deaths in the placebo group. CONCLUSIONS: This trial of thromboprophylaxis in medically ill, hospitalized older adults did not demonstrate that enoxaparin reduced the risk of symptomatic VTE after 1 month. Because the trial was prematurely discontinued, larger trials are needed to definitively address this question. (Funded by the French Ministry of Health Programme Hospitalier de Recherche Clinique, grant number PHRC-N-13-0283; ClinicalTrials.gov number, NCT02379806.)
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Enoxaparina , Tromboembolia Venosa , Idoso , Humanos , Anticoagulantes , Pacientes , Tromboembolia Venosa/tratamento farmacológicoRESUMO
Power consumption, thermal management, and wiring challenge of the binary serial architecture drive the search for alternative paradigms to computing. Of special interest is neuromorphic computing, in which materials and device structures are designed to mimic neuronal functionalities with energy-efficient non-linear responses and both short- and long-term plasticities. In this work, we explore and report on the enabling potential of single-electron tunneling (SET) in PbS nanoplatelets epitaxially grown in the liquid phase on InP, which present these key features. By extrapolating the experimental data in the SET regime, we predict and model synaptic operations. The low-energy (
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Semiconductor nanoplatelets, which offer a compelling combination of the flatness of two-dimensional semiconductors and the inherent richness brought about by colloidal nanostructure synthesis, form an ideal and general testbed to investigate fundamental physical effects related to the dimensionality of semiconductors. With low temperature scanning tunnelling spectroscopy and tight binding calculations, we investigate the conduction band density of states of individual CdSe nanoplatelets. We find an occurrence of peaks instead of the typical steplike function associated with a quantum well, that rule out a free in-plane electron motion, in agreement with the theoretical density of states. This finding, along with the detection of deep trap states located on the edge facets, which also restrict the electron motion, provides a detailed picture of the actual lateral confinement in quantum wells with finite length and width.
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Electron states in semiconductor materials can be modified by quantum confinement. Adding to semiconductor heterostructures the concept of lateral geometry offers the possibility to further tailor the electronic band structure with the creation of unique flat bands. Using block copolymer lithography, we describe the design, fabrication, and characterization of multiorbital bands in a honeycomb In0.53Ga0.47As/InP heterostructure quantum well with a lattice constant of 21 nm. Thanks to an optimized surface quality, scanning tunnelling spectroscopy reveals the existence of a strong resonance localized between the lattice sites, signature of a p-orbital flat band. Together with theoretical computations, the impact of the nanopatterning imperfections on the band structure is examined. We show that the flat band is protected against the lateral and vertical disorder, making this industry-standard system particularly attractive for the study of exotic phases of matter.
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Semiconductor nanocrystalline heterostructures can be produced by the immersion of semiconductor substrates into an aqueous precursor solution, but this approach usually leads to a high density of interfacial traps. In this work, we study the effect of a chemical passivation of the substrate prior to the nanocrystalline growth. PbS nanoplatelets grown on sulfur-treated InP (001) surfaces at temperatures as low as 95 °C exhibit abrupt crystalline interfaces that allow a direct and reproducible electron transfer to the InP substrate through the nanometer-thick nanoplatelets with scanning tunnelling spectroscopy. It is in sharp contrast with the less defined interface and the hysteresis of the current-voltage characteristics found without the passivation step. Based on a tunnelling effect occurring at energies below the bandgap of PbS, we show the formation of a type II, trap-free, epitaxial heterointerface, with a quality comparable to that grown on a nonreactive InP (110) substrate by molecular beam epitaxy. Our scheme offers an attractive alternative to the fabrication of semiconductor heterostructures in the gas phase.