EBioMedicine最新文献

{"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":"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":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743550/pdf/","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":"OA","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":"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":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732148/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome and metabolomics reveal the effect of gut microbiota on liver regeneration of fatty liver disease.","authors":"Yiqing Hu, Xiaoyi Hu, Li Jiang, Jia Luo, Jiacheng Huang, Yaohan Sun, Yinbiao Qiao, Hao Wu, Shijie Zhou, Haoyu Li, Jianhui Li, Lin Zhou, Shusen Zheng","doi":"10.1016/j.ebiom.2024.105482","DOIUrl":"10.1016/j.ebiom.2024.105482","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with impaired regenerative capacity and poor postoperative prognosis following hepatectomy. Previous research has highlighted the importance of the gut-liver axis in the physiological and pathological processes of the liver. However, the contribution of gut bacteria to the regeneration of livers with MAFLD and its metabolic regulatory mechanisms remain elusive.</p><p><strong>Methods: </strong>Partial hepatectomy (PHx) was performed on C57Bl/6J mice fed with high-fat diet (HFD) for 12 weeks. Pathological examination, immunohistochemistry, and qRT-PCR analysis were performed to assess the severity of steatosis and proliferative potential. The gut microbiome was examined by 16S rRNA gene sequencing and shotgun metagenomics, whereas liver metabolomics was analysed via untargeted and targeted metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS).</p><p><strong>Findings: </strong>HFD-induced hepatic steatosis in mice led to impaired liver regeneration following PHx. The gut microbiota and liver metabolites were altered along with the liver regeneration process. Longitudinal time-series analysis revealed dynamic alterations in these data, whereas correlation analysis screened out bacterial candidates that potentially influence liver regeneration in MAFLD by modulating metabolic pathways. Among these bacteria, the dominant bacterium Akkermansia was selected for subsequent investigation. MAFLD mice gavaged with Akkermansia muciniphila (A. muciniphila) exhibited reduced liver lipid accumulation and accelerated liver regeneration, possibly through the regulation of the tricarboxylic acid (TCA) cycle.</p><p><strong>Interpretation: </strong>These data demonstrated the interplay between the gut microbiome, liver metabolomics, and liver regeneration in mice with MAFLD. A. muciniphila has the potential to serve as a clinical intervention agent to accelerate postoperative recovery in MAFLD.</p><p><strong>Funding: </strong>This work was supported by the Research Project of Jinan Microecological Biomedicine Shandong Laboratory [JNL-2022008B]; the Zhejiang Provincial Natural Science Foundation of China [LZ21H180001]; the Fundamental Research Funds for the Central Universities [No. 2022ZFJH003].</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105482"},"PeriodicalIF":9.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Annotation-free artificial intelligence for abdominal computed tomography anomaly detection.","authors":"Jia Fu, Mengjie Fang, Zhuozhao Zheng, Di Dong","doi":"10.1016/j.ebiom.2024.105497","DOIUrl":"10.1016/j.ebiom.2024.105497","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105497"},"PeriodicalIF":9.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing artificial intelligence for mental health care.","authors":"eBioMedicine","doi":"10.1016/j.ebiom.2025.105563","DOIUrl":"https://doi.org/10.1016/j.ebiom.2025.105563","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105563"},"PeriodicalIF":9.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002168","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":"The impact of information and communication technology on immunisation and immunisation programmes in low-income and middle-income countries: a systematic review and meta-analysis.","authors":"Mohini Zarekar, Hussein Al-Shehabi, Rita Dörner, Heide Weishaar, Tessa Lennemann, Charbel El Bcheraoui, Andrea Bernasconi","doi":"10.1016/j.ebiom.2024.105520","DOIUrl":"10.1016/j.ebiom.2024.105520","url":null,"abstract":"<p><strong>Background: </strong>Low-income and Middle-income Countries (LMIC) are continually working to ensure everyone can access life-saving vaccines. Recognising the considerable impact of Information and Communication Technology (ICT) in healthcare, we performed a systematic review and meta-analysis to summarise ICT effectiveness in improving vaccine delivery in LMICs.</p><p><strong>Methods: </strong>A systematic search from January 2010 to August 2023 in MEDLINE, EMBASE, Cochrane Library, BMJ Health & Care Informatics, and grey literature was performed. This search focused on randomised controlled trials (RCTs), non-RCTs, observational, and mixed-methods studies in English, examining ICT's effects on childhood immunisation in LMICs. Risk of bias in RCTs and non-RCTs was assessed using the Joanna Briggs Institute tool, and mixed-methods studies were evaluated with the Mixed Methods Appraisal Tool. A meta-analysis summarised ICT's impact on third pentavalent dose coverage and full immunisation by age one. The study is registered with PROSPERO (CRD42023446062).</p><p><strong>Findings: </strong>Of 6535 screened studies, 27 involving 354,979 children were included. All apart from one study demonstrated a positive impact on immunisation coverage and timeliness, completeness and accuracy of records, number of adverse events reporting, vaccine stockouts, and cold chain expansion. The meta-analysis demonstrated that reminders effectively improved coverage rate of the third dose of the pentavalent vaccine (OR 2.32, 95% CI 1.34-4.03) and the full immunisation at one year of age (OR 2.61, 95% CI 1.2-5.67) with significant degrees of heterogeneity, respectively I² 82% and I² 89%. Main concerns for bias in RCTs included unblinded outcome assessors and intervention providers. Interpreting quasi-experimental studies was more challenging due to the higher risk of baseline differences between study arms, statistical methods, and dropouts. Mixed-methods studies often lacked clarity in integrating qualitative and quantitative data.</p><p><strong>Interpretation: </strong>This systematic review confirms the benefits of ICT in immunisation programmes by enhancing various stages of vaccine delivery. Specifically, reminders have been shown to enhance childhood immunisation coverage rates.</p><p><strong>Funding: </strong>Deutsche Gesellschaft für Internationale Zusammenarbeit (German Corporation for International Cooperation, GIZ) as part of the Digital Innovation in Pandemic Control (DIPC) Initiative, financed by the Bundesministerium für Wirtschaftliche Zusammenarbeit (Federal Ministry for Economic Cooperation and Development, BMZ).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105520"},"PeriodicalIF":9.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicry.","authors":"Xin Ma, Jian Zhang, Qianling Jiang, Yong-Xin Li, Guan Yang","doi":"10.1016/j.ebiom.2024.105516","DOIUrl":"10.1016/j.ebiom.2024.105516","url":null,"abstract":"<p><strong>Background: </strong>Gut commensal microbiota has been identified as a potential environmental risk factor for multiple sclerosis (MS), and numerous studies have linked the commensal microorganism with the onset of MS. However, little is known about the mechanisms underlying the gut microbiome and host-immune system interaction.</p><p><strong>Methods: </strong>We employed bioinformatics methodologies to identify human microbial-derived peptides by analyzing their similarity to the MHC II-TCR binding patterns of self-antigens. Subsequently, we conducted a range of in vitro and in vivo assays to assess the encephalitogenic potential of these microbial-derived peptides.</p><p><strong>Findings: </strong>We analyzed 304,246 human microbiome genomes and 103 metagenomes collected from the MS cohort and identified 731 nonredundant analogs of myelin oligodendrocyte glycoprotein peptide 35-55 (MOG_35-55). Of note, half of these analogs could bind to MHC II and interact with TCR through structural modeling of the interaction using fine-tuned AlphaFold. Among the 8 selected peptides, the peptide (P3) shows the ability to activate MOG_35-55-specific CD4⁺ T cells in vitro. Furthermore, P3 shows encephalitogenic capacity and has the potential to induce EAE in some animals. Notably, mice immunized with a combination of P3 and MOG_35-55 develop severe EAE. Additionally, dendritic cells could process and present P3 to MOG_35-55-specific CD4⁺ T cells and activate these cells.</p><p><strong>Interpretation: </strong>Our data suggests the potential involvement of a MOG_35-55-mimic peptide derived from the gut microbiota as a molecular trigger of EAE pathogenesis. Our findings offer direct evidence of how microbes can initiate the development of EAE, suggesting a potential explanation for the correlation between certain gut microorganisms and MS prevalence.</p><p><strong>Funding: </strong>National Natural Science Foundation of China (82371350 to GY).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105516"},"PeriodicalIF":9.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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":"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":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732195/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust, fully-automated assessment of cerebral perivascular spaces and white matter lesions: a multicentre MRI longitudinal study of their evolution and association with risk of dementia and accelerated brain atrophy.","authors":"Giuseppe Barisano, Michael Iv, Jeiran Choupan, Melanie Hayden-Gephart","doi":"10.1016/j.ebiom.2024.105523","DOIUrl":"10.1016/j.ebiom.2024.105523","url":null,"abstract":"<p><strong>Background: </strong>Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility.</p><p><strong>Methods: </strong>We developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer's Disease Neuroimaging Initiative, the National Alzheimer's Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models.</p><p><strong>Findings: </strong>Our fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer's disease biomarkers.</p><p><strong>Interpretation: </strong>These robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia.</p><p><strong>Funding: </strong>US National Institutes of Health.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105523"},"PeriodicalIF":9.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk tools.","authors":"Michail Kokkorakis, Pytrik Folkertsma, Filippos Anagnostakis, Nicole Sirotin, Manyoo Agarwal, Ronney Shantouf, Robert H Henning, Hanno Pijl, Bruce H R Wolffenbuttel, Jeroen J Bax, Douwe E Atsma, José Castela Forte, Christos S Mantzoros, Sipko van Dam","doi":"10.1016/j.ebiom.2024.105518","DOIUrl":"10.1016/j.ebiom.2024.105518","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Coronary artery disease (CAD) comprises one of the leading causes of morbidity and mortality both in the European population and globally. All established clinical risk stratification scores and models require blood lipids and physical measurements. The latest reports of the European Commission suggest that attracting health professionals to collect these data can be challenging, both from a logistic and cost perspective, which limits the usefulness of established models and makes them unsuitable for population-wide screening in resource-limited settings, i.e., rural areas. Therefore, the aim of this study was to develop and externally validate a questionnaire-based risk stratification model on a population scale at minimal cost, i.e., the Questionnaire-Based Evaluation for Estimating Coronary Artery Disease (QUES-CAD) to stratify the 10-year incidence of coronary artery disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Cox proportional hazards (CoxPH) and Cox gradient boosting (CoxGBT) models were trained with 10-fold cross-validation using combinations of ten questionnaire variables on the White population of the UK Biobank (n = 448,818) and internally validated the models in all ethnic minorities (n = 27,433). The Lifelines cohort was employed as an independent external validation population (n = 97,770). Additionally, we compared QUES-CAD's performance, containing only questionnaire variables, to clinically established risk prediction tools, i.e., Framingham Coronary Heart Disease Risk Score, American College of Cardiology/American Heart Association pooled cohort equation, World Health Organization cardiovascular disease risk charts, and Systematic Coronary Risk Estimation 2 (SCORE2). We conducted partial log-likelihood ratio (PLR) tests and C-index comparisons between QUES-CAD and established clinical prediction models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;In the external validation set, QUES-CAD exhibited C-index values of CoxPH: 0.692 (95% Confidence Interval [CI]: 0.673-0.71) and CoxGBT: 0.699 (95% CI: 0.681-0.717) for the male population and CoxPH: 0.771 (95% CI: 0.748-0.794) and CoxGBT: 0.759 (95% CI: 0.736-0.783) for the female population. The addition of measurement-based variables and variables that require a prior medical examination (i.e., insulin use, number of treatments/medications taken, prevalent cardiovascular disease [other than CAD, and stroke diagnosed by a doctor]) and the further addition of biomarkers/other measurements (i.e., high-density lipoprotein [HDL] cholesterol, total cholesterol, and glycated haemoglobin) did not significantly improve QUES-CAD's performance in most instances. C-index comparisons and PLR tests showed that QUES-CAD performs and fits the data at least as well as the clinical prediction models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;QUES-CAD performs comparably to established clinical prediction models and enables a population-wide identification of high-risk individuals for CAD.","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"111 ","pages":"105518"},"PeriodicalIF":9.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}