EBioMedicine最新文献

{"title":"Safety of baricitinib in vaccinated patients with severe and critical COVID-19 sub study of the randomised Bari-SolidAct trial.","authors":"Hans-Kittil Viermyr, Kristian Tonby, Erica Ponzi, Sophie Trouillet-Assant, Julien Poissy, José R Arribas, Virginie Dyon-Tafani, Maude Bouscambert-Duchamp, Lambert Assoumou, Bente Halvorsen, Nuriye Basdag Tekin, Alpha Diallo, Lucie De Gastines, Ludvig A Munthe, Sarah Louise Murphy, Thor Ueland, Annika E Michelsen, Fridtjof Lund-Johansen, Pål Aukrust, Joy Mootien, Benjamin Dervieux, Yoann Zerbib, Jean-Christophe Richard, Renaud Prével, Denis Malvy, Jean-François Timsit, Nathan Peiffer-Smadja, Damien Roux, Lionel Piroth, Hafid Ait-Oufella, Cesar Vieira, Olav Dalgard, Lars Heggelund, Karl Erik Müller, Jannicke Horjen Møller, Anders Benjamin Kildal, Vegard Skogen, Saad Aballi, Jonas Daniel Sjøberg Øgaard, Anne Ma Dyrhol-Riise, Anders Tveita, Amin Alirezaylavasani, Dominique Costagliola, Yazdan Yazdanpanah, Inge Christoffer Olsen, Tuva Børresdatter Dahl, Hassen Kared, Aleksander Rygh Holten, Marius Trøseid","doi":"10.1016/j.ebiom.2024.105511","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105511","url":null,"abstract":"<p><strong>Background: </strong>The Bari-SolidAct randomized controlled trial compared baricitinib with placebo in patients with severe COVID-19. A post hoc analysis revealed a higher incidence of serious adverse events (SAEs) among SARS-CoV-2-vaccinated participants who had received baricitinib. This sub-study aimed to investigate whether vaccination influences the safety profile of baricitinib in patients with severe COVID-19.</p><p><strong>Methods: </strong>Biobanked samples from 146 participants (55 vaccinated vs. 91 unvaccinated) were analysed longitudinally for inflammation markers, humoral responses, tissue viral loads, and plasma viral antigens on days 1, 3, and 8. High-dimensional analyses, including RNA sequencing and flow cytometry, were performed on available samples. Mediation analyses were used to assess relationships between SAEs, baseline-adjusted biomarkers, and treatment-vaccination status.</p><p><strong>Findings: </strong>Vaccinated participants were older, more frequently hospitalized, had more comorbidities, and exhibited higher nasopharyngeal viral loads. Baricitinib treatment did not affect antibody responses or viral clearance, but reduced markers of T-cell and monocyte activation compared to placebo (sCD25, sCD14, sCD163, sTIM-3). Age, baseline levels of plasma viral antigen, and several inflammatory markers, as well as IL-2, IL-6, Neopterin, CXCL16, sCD14, and suPAR on day 8 were associated with the occurrence of SAEs. However, mediation analyses of markers linked to SAEs, baricitinib treatment, or vaccination status did not reveal statistically significant interactions between vaccination status and SAEs.</p><p><strong>Interpretation: </strong>This sub-study did not identify any virus- or host-related biomarkers significantly associated with the interaction between SARS-CoV-2 vaccination status and the safety of baricitinib. However, caution should be exercised due to the moderate sample size.</p><p><strong>Funding: </strong>EU Horizon 2020 (grant number 101015736).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105511"},"PeriodicalIF":9.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to Multiomic analysis in fibroblasts of patients with inborn errors of cobalamin metabolism reveals concordance with clinical and metabolic variability [eBioMedicine 99 (2024), 104911].","authors":"Arnaud Wiedemann, Abderrahim Oussalah, Rosa-Maria Guéant Rodriguez, Elise Jeannesson, Marc Merten, Irina Rotaru, Jean-Marc Alberto, Okan Baspinar, Charif Rashka, Ziad Hassan, Youssef Siblini, Karim Matmat, Manon Jeandel, Celine Chery, Aurélie Robert, Guillaume Chevreux, Laurent Lignières, Jean-Michel Camadro, François Feillet, David Coelho, Jean-Louis Guéant","doi":"10.1016/j.ebiom.2024.105540","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105540","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"112 ","pages":"105540"},"PeriodicalIF":9.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics profiling reveals altered mitochondrial metabolism in adipose tissue from patients with metabolic dysfunction-associated steatohepatitis.","authors":"Helena Castañé, Andrea Jiménez-Franco, Anna Hernández-Aguilera, Cristian Martínez-Navidad, Vicente Cambra-Cortés, Alina-Iuliana Onoiu, Juan Manuel Jiménez-Aguilar, Marta París, Mercè Hernández, David Parada, Carmen Guilarte, Antonio Zorzano, María Isabel Hernández-Alvarez, Jordi Camps, Jorge Joven","doi":"10.1016/j.ebiom.2024.105532","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105532","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form steatohepatitis (MASH) contribute to rising morbidity and mortality rates. The storage of fat in humans is closely associated with these diseases' progression. Thus, adipose tissue metabolic homeostasis could be key in both the onset and progression of MASH.</p><p><strong>Methods: </strong>We conducted a case-control observational research using a systems biology-based approach to analyse liver, abdominal subcutaneous adipose tissue (SAT), omental visceral adipose tissue (VAT), and blood of n = 100 patients undergoing bariatric surgery (NCT05554224). MASH was diagnosed through histologic assessment. Whole-slide image analysis, lipidomics, proteomics, and transcriptomics were performed on tissue samples. Lipidomics and proteomics profiles were determined on plasma samples.</p><p><strong>Findings: </strong>Liver transcriptomics, proteomics, and lipidomics revealed interconnected pathways associated with inflammation, mitochondrial dysfunction, and lipotoxicity in MASH. Paired adipose tissue biopsies had larger adipocyte areas in both fat depots in MASH. Enrichment analyses of proteomics and lipidomics data confirmed the association of liver lesions with mitochondrial dysfunction in VAT. Plasma lipidomics identified candidates with high diagnostic accuracy (AUC = 0.919, 95% CI 0.840-0.979) for screening MASH.</p><p><strong>Interpretation: </strong>Mitochondrial dysfunction is also present in VAT in patients with obesity-associated MASH. This may cause a disruption in the metabolic equilibrium of lipid processing and storage, which impacts the liver and accelerates detrimental adaptative responses.</p><p><strong>Funding: </strong>The project leading to these results has received funding from 'la Caixa' Foundation (HR21-00430), and from the Instituto de Salud Carlos III (ISCIII) (PI21/00510) and co-funded by the European Union.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105532"},"PeriodicalIF":9.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared genetic architecture and bidirectional clinical risks within the psycho-metabolic nexus.","authors":"Xiaonan Guo, Yu Feng, Xiaolong Ji, Ningning Jia, Aierpati Maimaiti, Jianbo Lai, Zheng Wang, Sheng Yang, Shaohua Hu","doi":"10.1016/j.ebiom.2024.105530","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105530","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence suggests a complex interplay between psychiatric disorders and metabolic dysregulations. However, most research has been limited to specific disorder pairs, leaving a significant gap in our understanding of the broader psycho-metabolic nexus.</p><p><strong>Methods: </strong>This study leveraged large-scale cohort data and genome-wide association study (GWAS) summary statistics, covering 8 common psychiatric disorders and 43 metabolic traits. We introduced a comprehensive analytical strategy to identify shared genetic bases sequentially, from key genetic correlation regions to local pleiotropy and pleiotropic genes. Finally, we developed polygenic risk score (PRS) models to translate these findings into clinical applications.</p><p><strong>Findings: </strong>We identified significant bidirectional clinical risks between psychiatric disorders and metabolic dysregulations among 310,848 participants from the UK Biobank. Genetic correlation analysis confirmed 104 robust trait pairs, revealing 1088 key genomic regions, including critical hotspots such as chr3: 47588462-50387742. Cross-trait meta-analysis uncovered 388 pleiotropic single nucleotide variants (SNVs) and 126 shared causal variants. Among variants, 45 novel SNVs were associated with psychiatric disorders and 75 novel SNVs were associated with metabolic traits, shedding light on new targets to unravel the mechanism of comorbidity. Notably, RBM6, a gene involved in alternative splicing and cellular stress response regulation, emerged as a key pleiotropic gene. When psychiatric and metabolic genetic information were integrated, PRS models demonstrated enhanced predictive power.</p><p><strong>Interpretation: </strong>The study highlights the intertwined genetic and clinical relationships between psychiatric disorders and metabolic dysregulations, emphasising the need for integrated approaches in diagnosis and treatment.</p><p><strong>Funding: </strong>The National Key Research and Development Program of China (2023YFC2506200, SHH). The National Natural Science Foundation of China (82273741, SY).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105530"},"PeriodicalIF":9.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From intensive care monitors to cloud environments: a structured data pipeline for advanced clinical decision support.","authors":"Sijm H Noteboom, Eline Kho, Maria Galanty, Clara I Sánchez, Frans C P Ten Bookum, Denise P Veelo, Alexander P J Vlaar, Björn J P van der Ster","doi":"10.1016/j.ebiom.2024.105529","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105529","url":null,"abstract":"<p><strong>Background: </strong>Clinical decision-making is increasingly shifting towards data-driven approaches and requires large databases to develop state-of-the-art algorithms for diagnosing, detecting and predicting diseases. The intensive care unit (ICU), a data-rich setting, faces challenges with high-frequency, unstructured monitor data. Here, we showcase a successful example of a data pipeline to efficiently move patient data to the cloud environment for structured storage. This supports individual patient analysis, enables largescale retrospective research, and the development of data-driven algorithms.</p><p><strong>Methods: </strong>Since June 2021, ICU data of the Amsterdam UMC have been collected and stored in a third-party cloud environment which is hosted on large virtual servers. The feasibility of the pipeline will be demonstrated with the available data through research and clinical use cases. Furthermore, privacy, safety, data quality, and environmental impact are carefully considered in the cloud storage transition.</p><p><strong>Findings: </strong>Over two years, data from over 9000 patients have been stored in the cloud. The availability, agility, computational power, high uptime, and streaming data pipelines allow for large retrospective analyses as well as the opportunity to implement real-time prediction of critical events with machine learning algorithms. Critical events can be accessed by applying keyword search in the natural language data, annotated by the treating team. Besides, the cloud environment offers storage of institutional data enabling evaluation of healthcare.</p><p><strong>Interpretation: </strong>The combined data and features of cloud environments offer support for predictive algorithm development and implementation, healthcare evaluation, and improved individual patient care.</p><p><strong>Funding: </strong>University of Amsterdam Research Priority Agenda Program AI for Heath Decision-Making.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105529"},"PeriodicalIF":9.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to-\"Ca²⁺ and CACNA1H mediate targeted suppression of breast cancer brain metastasis by AM RF EMF\"-[eBiomedicine, 44 (2019) 194-208].","authors":"Sambad Sharma, Shih-Ying Wu, Hugo Jimenez, Fei Xing, Dongqin Zhu, Yin Liu, Kerui Wu, Abhishek Tyagi, Dan Zhao, Hui-Wen Lo, Linda Metheny-Barlow, Peiqing Sun, Daniel J Bourland, Michael D Chan, Alexandra Thomas, Alexandre Barbault, Ralph B D'Agostino, Christopher T Whitlow, Volker Kirchner, Carl Blackman, Boris Pasche, Kounosuke Watabe","doi":"10.1016/j.ebiom.2024.105541","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105541","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105541"},"PeriodicalIF":9.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yield of clinical metagenomics: insights from real-world practice for tissue infections.","authors":"Hui Tang, Yuqing Chen, Xinyan Tang, Muyun Wei, Juan Hu, Xuan Zhang, Dairong Xiang, Qing Yang, Dongsheng Han","doi":"10.1016/j.ebiom.2024.105536","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105536","url":null,"abstract":"<p><strong>Background: </strong>While metagenomic next-generation sequencing (mNGS) has been acknowledged as a valuable diagnostic tool for infections, its clinical validity and impact on patient management when using fresh tissue samples remains uncertain.</p><p><strong>Methods: </strong>We conducted a retrospective cross-sectional study involving patients who underwent tissue mNGS at a tertiary hospital in China from February 2021 to February 2024, aiming to assess its ability to detect plausible pathogens and its clinical validity and impact.</p><p><strong>Findings: </strong>A total of 520 mNGS results from 508 patients were analysed, detecting plausible pathogens in 302 (58.1%) tests, including 260 single-pathogen and 42 (13.9%) multi-pathogen results. Rare pathogens, such as Balamuthia mandrillaris, Bartonella henselae, and Sporothrix globosa, were identified. Of the multi-pathogen results, 22 were with predominance of anaerobes. mNGS showed higher positivity in cases with high initial suspicion of infection than those used for ruling out infection (PR 1.961, 95% CI: 1.604-2.394) and in patients living with HIV (PR 1.312, 95% CI: 1.047-1.643) or solid organ transplant recipients (PR 1.346, 95% CI: 1.103-1.643) compared to immunocompetent individuals. Sensitivity and specificity for diagnosing confirmed/probable infections were 85.0% (95% CI: 76.7%-93.3%) and 93.7% (95% CI: 86.8%-100.0%), respectively. mNGS influenced clinical management in 258 (49.6%) cases by identifying new infections and in 112 (21.5%) by excluding infections. It prompted initiation (20.2%), modification (23.1%), or discontinuation (6.3%) of antimicrobial therapy.</p><p><strong>Interpretation: </strong>mNGS demonstrates high diagnostic accuracy for tissue infections. Its impact on clinical management highlights the need to integrate it into current diagnostic practices.</p><p><strong>Funding: </strong>National Natural Science Foundation of China (No. 82472371), \"Leading Geese\" Research and Development Plan of Zhejiang Province (No. 2024C03218), and Pudong New Area Joint Project (PW2021D-09).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105536"},"PeriodicalIF":9.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ex vivo imaging-based high content phenotyping of patients with rheumatoid arthritis.","authors":"Felix Kartnig, Michael Bonelli, Ulrich Goldmann, Noemi Mészáros, Nikolaus Krall, Daniel Aletaha, Leonhard X Heinz, Giulio Superti-Furga","doi":"10.1016/j.ebiom.2024.105522","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105522","url":null,"abstract":"<p><strong>Background: </strong>High content imaging-based functional precision medicine approaches have been developed and successfully applied in the field of haemato-oncology. For rheumatoid arthritis (RA), treatment selection is still based on a trial-and-error principle, and biomarkers for patient stratification and drug response prediction are needed.</p><p><strong>Methods: </strong>A high content, high throughput microscopy-based phenotyping pipeline for peripheral blood mononuclear cells (PBMCs) was developed, allowing for the quantification of cell type frequencies, cell type specific morphology and intercellular interactions from patients with RA (n = 65) and healthy controls (HC, n = 33). Samples were exposed to a curated set of RA-specific small molecules, biologicals and reference stimuli for 24 h to assess ex vivo drug effects. Data on ex vivo PBMC phenotypes were integrated with information on patients' in vivo medication and disease activity.</p><p><strong>Findings: </strong>The unbiased data from in total 6.9e8 individual cells were collected and allowed for the identification of PBMC phenotypes specific to disease activity as well as in vivo and ex vivo treatment. The arrayed ex vivo drug perturbation enabled the systematic characterization of drug effects, clustering by mode of action and uncovered morphologic alterations associated with biologic disease-modifying anti-rheumatic drug (DMARD) treatment. Individual in vivo treatment regimens translated into altered immune cell abundances in patients with a comedication of conventional synthetic DMARDs when compared to HCs. Global integration of PBMC characteristics led to clustering of patients according to disease activity and correlation with clinical data.</p><p><strong>Interpretation: </strong>The application of the developed screening tool demonstrates a technical proof-of-concept for feasibility of a functional precision medicine approach to the ex vivo immunophenotypic characterisation of patients with RA.</p><p><strong>Funding: </strong>This work was supported by the Austrian Academy of Sciences, the Medical University of Vienna and a grant (RMG2235 to L.X.H.) from the European Alliance of Associations for Rheumatology (EULAR).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105522"},"PeriodicalIF":9.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic risk score to the rescue of monogenic diseases? The case of epilepsy.","authors":"Jean-Madeleine De Sainte Agathe, Eric Leguern","doi":"10.1016/j.ebiom.2024.105505","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105505","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105505"},"PeriodicalIF":9.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of microvascular flow in human atherosclerotic carotid plaques using ultrasound localization microscopy.","authors":"Henri Leroy, Louise Z Wang, Anatole Jimenez, Nassim Mohamedi, Clément Papadacci, Pierre Julia, Salma El Batti, Jean-Marc Alsac, Jonas Sitruk, Armelle Arnoux, Patrick Bruneval, Emmanuel Messas, Tristan Mirault, Guillaume Goudot, Mathieu Pernot","doi":"10.1016/j.ebiom.2024.105528","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105528","url":null,"abstract":"<p><strong>Background: </strong>Neovascularisation of carotid plaques contributes to their vulnerability. Current imaging methods such as contrast-enhanced ultrasound (CEUS) usually lack the required spatial resolution and quantification capability for precise neovessels identification. We aimed at quantifying plaque vascularisation with ultrasound localization microscopy (ULM) and compared the results to histological analysis.</p><p><strong>Methods: </strong>We conducted a prospective, monocentric, study involving patients who were undergoing carotid endarterectomy (CEA) for carotid artery stenosis. The day before CEA ultrasound examination coupled with the injection of microbubbles (MB) as a contrast agent (CEUS) to image the MB circulating within and around the carotid plaque was performed. CEUS images analysis classified patients into 2 groups: absence of neovascularisation (group A) or presence of neovascularisation (group B). ULM was performed by localising and tracking individual MB centres to reconstruct the neovessels structure with a resolution of around 60 μm. Plaques were manually segmented on the images to quantify the number of neovessels and various haemodynamic metrics inside the plaques. Histological analysis of the excised carotid plaque specimens classified patients into 2 groups: absence of neovascularisation (group I) or presence of neovascularisation (group II).</p><p><strong>Findings: </strong>Among the 26 patients included, classification was as follows: group I: n = 8 and group II: n = 18, 18 patients had analysable CEUS images and were classified as follows: group A: n = 10, group B: n = 8. The median (Q1-Q3) number of MB tracked per second inside the plaque was 0.03 (0-0.37) for patients in group I and 0.51 (0-3) for patients in group A versus (vs.) 3.55 (1.26-17.68) for patients in group II and 9.69 (5.83-34.68) for patients in group B (p = 0.00049; p = 0.010 respectively). The length of the MB tracks was 0.02 mm (0-0.16) in group I vs. 0.29 mm (0.22-0.45) in group II (p = 0.0069). The study also showed that flow in the neovessels was greater during systole than during diastole period: 9.38 (1.67-19.17) MB tracked per second vs. 1.35 (0.28-6.56) (p = 0.021).</p><p><strong>Interpretation: </strong>ULM allows the detection of neovessels within the carotid atherosclerotic plaque. Thus, ULM provides a precise picture of plaque neovascularisation in patients and could be used as a non-invasive imaging technique to assess carotid plaque vulnerability.</p><p><strong>Funding: </strong>The study was sponsored and funded by Assistance Publique-Hôpitaux de Paris (CRC 1806 APHP INNOVATION 2018). Co-funding by ART (Technological Research Accelerator) biomedical ultrasound program of INSERM, France.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105528"},"PeriodicalIF":9.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}