BMC Medicine最新文献

{"title":"Outcomes and cost-effectiveness of an integrated holistic care package on persons affected by podoconiosis, lymphatic filariasis and leprosy and community members in north-western Ethiopia: an implementation research study.","authors":"Oumer Ali, Awoke Mihretu, Natalia Hounsome, Vasso Anagnostopoulou, Stephen A Bremner, Mersha Kinfe, Asrat Mengiste, Maya Semrau, Abebaw Fekadu, Gail Davey","doi":"10.1186/s12916-025-04108-9","DOIUrl":"10.1186/s12916-025-04108-9","url":null,"abstract":"<p><strong>Background: </strong>Most studies on integration of neglected tropical disease programmes have focused on mass drug administration or environmental measures rather than Disease Management, Disability and Inclusion (DMDI). The study reported here explored integration of a DMDI care package across three disabling, stigmatising neglected tropical diseases (podoconiosis, lymphatic filariasis and leprosy), across physical and mental health, and into the state health system.</p><p><strong>Methods: </strong>We conducted this pre-post study, the third phase of an implementation research project, in two predominantly rural districts in north-west Ethiopia in 2021. We assessed physical and mental health outcomes on 192 affected persons and 817 community members at baseline and 6 months after initiation of the integrated care package, implemented by nurses and health officers. Key outcomes measured were disability (using WHODAS-2.0), depression (Patient Health Questionnaire-9), discrimination (Discrimination and Stigma Scale), internalised stigma (Internalized Stigma Related to Lymphoedema), quality of life (Dermatology Life Quality Index) and social support (Oslo-3 Social Support Scale). Mixed effects linear regression models were used to estimate change in outcomes between baseline and 6 months after initiation of the care package. We also evaluated implementation feasibility and conducted cost-effectiveness analysis.</p><p><strong>Results: </strong>Among 221 patients, improvements were observed in foot (- 2.3 cm; 95% CI: - 2.2, - 1.8) and leg circumference (- 1.8 cm; - 2.0, - 1.7) and acute attacks (6.2; 0.0, 6.6); these were statistically significant at the 5% level. Reductions were seen in disability scores (- 6.5; - 7.6, - 5.5), depression (- 5.3; - 6.6, - 4.6), discrimination (- 3.3; - 4.2, - 2.3), internalised stigma (- 3.7; - 4.6, - 2.8), quality of life (- 4.0; - 4.8, - 3.2), and alcohol use (- 1.6; - 2.4, - 0.8). No notable changes were found in the presence of wounds or moss, or perceived social support. Across 817 community members, there was strong evidence that knowledge improved, and stigmatising attitudes and social distance reduced. The intervention was cost-effective in reducing depression and disability and improving health-related quality of life and feasible to implement.</p><p><strong>Conclusion: </strong>The integrated intervention is feasible and cost-effective even in remote areas and appears ideal for scale-up to other endemic regions in Ethiopia and other countries.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"284"},"PeriodicalIF":7.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978378","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":"Higher adherence to the EAT-Lancet reference diet is inversely associated with mortality in a UK population of cancer survivors.","authors":"Nena Karavasiloglou, Alysha S Thompson, Giulia Pestoni, Flurina Suter, Keren Papier, Aedín Cassidy, Tilman Kühn, Sabine Rohrmann","doi":"10.1186/s12916-025-04106-x","DOIUrl":"10.1186/s12916-025-04106-x","url":null,"abstract":"<p><strong>Background: </strong>Significant advancements in treatment and care, as well as early detection, have contributed to an increase in cancer survival rates. Recently, the EAT-Lancet Commission on Food, Planet, Health proposed the \"planetary health diet\" but to date, no study has investigated the potential associations between adherence to the EAT-Lancet reference diet and mortality in cancer survivors. To determine whether higher adherence to the EAT-Lancet reference diet is associated with lower risk for all-cause, cancer, and cardiovascular mortality in cancer survivors.</p><p><strong>Methods: </strong>Data from the prospective UK Biobank study were used. Information from UK Biobank's Touchscreen questionnaire was used to develop a score reflecting adherence to the EAT-Lancet reference diet. Cox proportional hazards regression was used to assess the association of the EAT-Lancet reference diet score with all-cause, cancer, and cardiovascular mortality in cancer survivors.</p><p><strong>Results: </strong>Within 25,348 cancer survivors, better adherence to the EAT-Lancet reference diet was inversely related to all-cause mortality (hazard ratio (HR): 0.97, 95% confidence interval (CI): 0.95-0.99), 1 unit increase) and cancer mortality (HR: 0.98, 95% CI: 0.96-1.00), while mostly null associations were observed for major cardiovascular mortality (HR: 0.99, 95% CI: 0.95-1.03).</p><p><strong>Conclusions: </strong>Our findings suggest the adoption of the EAT-Lancet reference diet is associated with lower all-cause and cancer-specific mortality among cancer survivors.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"286"},"PeriodicalIF":7.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957424","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":"Phenotypic and genotypic characteristics of macrolide, lacosamide, and streptogramin resistance in clinically resistant Streptococci and their correlation with reduced biocide susceptibility.","authors":"Safaa A Abdel-Karim, Fathy M Serry, Eman M Elmasry, Wael A H Hegazy","doi":"10.1186/s12916-025-04097-9","DOIUrl":"10.1186/s12916-025-04097-9","url":null,"abstract":"<p><strong>Background: </strong>Gram-positive Streptococci is a huge group of different species that are classified based on its hemolytic effect besides the C-substance in the cell wall. This study focuses on the investigation of the prevalence and genetic basis of resistance to macrolides, lincosamides, and streptogramins (MLS) in α- and β-hemolytic Streptococci.</p><p><strong>Methods: </strong>Streptococcal isolates were identified and their resistance was assessed to MLS antibiotics through phenotypic analysis and genotypic screening of resistance genes. Isolates were also tested for susceptibility to antiseptics/disinfectants. The correlation between high MLS antibiotic resistance and reduced susceptibility to biocides was assessed. Efflux pump activity in the most resistant isolates (to both MLS antibiotics and biocides) was investigated.</p><p><strong>Results: </strong>The susceptibility testing indicates an increasing resistance to MLS, particularly macrolides (erythromycin, azithromycin, and clarithromycin) and lincomycin. By screening the resistance, the most predominant phenotype is the constitutive (cMLS) one, while the erm genes, particularly ermB, are the most detected genotype. Furthermore, the esterase-encoding gene ereA is widely distributed in the streptococcal isolates. By evaluating the minimum inhibitory concentrations (MICs) to different biocides, there was a strong relation between the increased MIC values to both MLS antibiotics and tested biocides. This can be attributed mainly to the transferable ermB gene and the enhanced bacterial efflux.</p><p><strong>Conclusions: </strong>A significant correlation exists between reduced biocide susceptibility and resistance to MLS antibiotics. Elevated efflux pump activity in MLS-resistant isolates suggests efflux mechanisms may contribute to dual resistance to antibiotics and biocides. However, cross-resistance is primarily driven by the horizontally transferable ermB gene, which confers resistance by targeting the 50S ribosomal subunit.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"281"},"PeriodicalIF":7.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062331","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":"Major depressive disorder recognition based on electronic handwriting recorded in psychological tasks.","authors":"Chong Li, Kunxue Zhang, Qunxing Lin, Shan Huang, Wanying Cheng, Yueshiyuan Lei, Xinyu Zhao, Jiubo Zhao","doi":"10.1186/s12916-025-04101-2","DOIUrl":"10.1186/s12916-025-04101-2","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to determine whether handwriting patterns are altered in individuals experiencing depressive episodes. Additionally, we developed a model for the recognition of major depressive disorder (MDD) based on electronic handwriting in psychological tasks.</p><p><strong>Methods: </strong>A total of 130 patients and 117 healthy controls completed 21 psychology-related handwriting tasks. The electronic tablet recorded several handwriting characteristics, including horizontal and vertical coordinates, nib pressure and speed, and inclination angle. The statistical indicators for each handwriting characteristic were calculated. Statistical analyses, including differential analysis, were performed to identify predictors of depression. Furthermore, logistic regression and machine learning models were developed to discriminate MDD.</p><p><strong>Results: </strong>The study included 130 patients with onset depression (mean (standard deviation (SD)) age, 20.42 (5.21)) and 117 healthy controls (mean (SD) age, 20.54 (2.60)). The t-test and logistics analysis results indicated that depressed patients exhibited a higher minimum of handwriting pressure, an elevated median of handwriting speed, and greater pen tip jitter. The LightGBM machine learning model exhibited satisfactory performance, with a cross-validated area under the receiver operating curve of mean 0.90 (SD, 0.01). The analysis of variance revealed that the negative question-answer task model exhibited superior performance compared to the neutral and positive task models.</p><p><strong>Conclusions: </strong>The present study indicates that depressed patients exhibit modal handwriting changes and developed a cost-effective, rapid, and valid model for identifying MDD. This finding established a strong foundation for developing multimodal recognition models in the future.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"282"},"PeriodicalIF":7.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962756","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":"Disease and mortality trajectories of cognitively able autistic individuals in mid- and later adulthood.","authors":"Yiwei Pu, Feng Li, Tailin Zhu, Jiong Li, Wei Zhou, Lingli Zhang, Jingyu Chen, Qianlong Zhang, Tai Ren, Fei Li","doi":"10.1186/s12916-025-04095-x","DOIUrl":"10.1186/s12916-025-04095-x","url":null,"abstract":"<p><strong>Background: </strong>An increasing number of autistic adults have entered their later life, but little is known about the disease trajectory in mid- and later adulthood. We aimed to examine the patterns of comorbidity progression in adults with autism spectrum disorder (ASD) that may affect their mortality.</p><p><strong>Methods: </strong>Participants were identified from the UK Biobank study. We first identified individuals with ASD diagnosis, each of whom was randomly matched to up to 10 participants without ASD diagnosis. Cox regression was used to estimate the hazard ratio (HR) of mortality. Disease trajectory analysis was performed to investigate temporal sequencing of medical conditions and mortality associated with ASD. A multistate model was used to investigate the association patterns between ASD and three common chronic conditions: cardiovascular disease/hypertension, type 2 diabetes and disorders of lipoprotein metabolism, and depression/anxiety.</p><p><strong>Results: </strong>The study included 659 ASD cases (66.8% male; mean age 52.0 [SD, 8.1]) and 6590 matched non-autistic individuals. ASD were associated with a 90% higher all-cause mortality (HR, 1.90, 95% CI, 1.41-2.55) and also higher risks of 45 medical conditions across almost all body systems (all Bonferroni-adjusted P < 0.05). Trajectory analyses exhibited three clusters of medical conditions that predisposed autistic adults to excess mortality: cardiometabolic diseases, external conditions, and infectious diseases. Autistic adults showed not only an overall increased risk of progression of multimorbidity but also distinctive association patterns across different disease transitions.</p><p><strong>Conclusions: </strong>Our findings show patterns of comorbidities among autistic adults in their mid- and later adulthood, which could provide information to their caregivers to implement appropriate disease management and prevention strategies.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"280"},"PeriodicalIF":7.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975307","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":"Understanding the underlying systems dynamics contributing to the continued predominance of the unhealthy motorway food environment in the Netherlands: identifying leverage points and actions for change.","authors":"Lisanne Geboers, Coosje Dijkstra, Frédérique C Rongen, Sanne K Djojosoeparto, Maartje P Poelman","doi":"10.1186/s12916-025-04088-w","DOIUrl":"10.1186/s12916-025-04088-w","url":null,"abstract":"<p><strong>Background: </strong>Motorway food environments are dominated by roadside restaurants and petrol station stores offering predominantly unhealthy quick-service meals and foods for on-the-go consumption. Improving these environments to promote healthier diets is necessary, but how to achieve this is not fully understood. Therefore, this study aims to identify the complex underlying systems dynamics contributing to the continued predominance of the unhealthy motorway food environment as well as to identify potential leverage points and corresponding actions for change to improve the healthiness of the motorway food environment.</p><p><strong>Methods: </strong>Two Group Model Building workshops were held in October 2023 with motorway food environment stakeholders (e.g. food providers, producers, national policymakers, truck drivers). In the first workshop, a Causal Loop Diagram (CLD) was created to identify the system that contributes to the continued predominance of the unhealthy motorway food environment. The research team then identified leverage points for change based on the CLD. During the second workshop, stakeholders formulated actions to improve the motorway food environment for each identified leverage point. Leverage points and actions were classified based on the Action Scales Model (ASM).</p><p><strong>Results: </strong>The resulting CLD comprised six interconnected subsystems (food providers, supply chain collaboration, government, social culture, road users, global trends) with six reinforcing feedback loops, underlying the continued predominance of the unhealthy motorway food environment. Additionally, 14 potential leverage points and 31 corresponding actions for change were identified at different levels of the system based on the ASM (i.e. events, structures, goals and beliefs).</p><p><strong>Conclusions: </strong>The findings show many interrelated factors and mechanisms underlying the continued predominance of the unhealthy motorway food environment. Actions for change were proposed together with stakeholders aimed at leverage points at different system levels. The results show that the motorway food environment is shaped by broader societal goals and beliefs (e.g. the profitability of unhealthy products) and social-cultural beliefs particularly evident to the on-the-go setting, including the motorway food environment. Together they present the strongest potential for leveraging systems change. There is a need for a coherent multidimensional action plan targeting these leverage points, which is broadly supported by various stakeholders, to induce systemic change.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"279"},"PeriodicalIF":7.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953835","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":"Gut microbiota-derived glutathione from metformin treatment alleviates intestinal ferroptosis induced by ischemia/reperfusion.","authors":"Fangyan Wang, Xinyu Wang, Chaoyi Wang, Wangxin Yan, Junpeng Xu, Zhengyang Song, Mingli Su, Jingjing Zeng, Qiannian Han, Gaoyi Ruan, Eryao Zhang, Wantie Wang","doi":"10.1186/s12916-025-04119-6","DOIUrl":"10.1186/s12916-025-04119-6","url":null,"abstract":"<p><strong>Background: </strong>Intestinal ischemia/reperfusion injury (IIRI) is a life-threatening condition caused by multiple organ and system failures induced by dysbiosis and gut leakage. Metformin has demonstrated efficacy in protecting against IIRI, although the precise role of the gut microbiota in the underlying mechanism is still ambiguous.</p><p><strong>Methods: </strong>This study examined intestinal barrier function and ferroptosis-related parameters in mice with IIRI following treatment with metformin. Additionally, dirty cages and antibiotics were utilized to investigate the impact of the microbiota on the effects of metformin. The analysis included an assessment of the microbial composition of metformin-treated mice and the biosynthetic activity of specific metabolites.</p><p><strong>Results: </strong>Metformin effectively reduced gut leakage induced by IIRI, as evidenced by decreased intestinal permeability and increased Occludin, ZO-1, Claudin-1, and MUC-1 expression. A decrease in the expression of the pro-ferroptotic proteins ACSL4, TFR1, and VDAC2/3 and a decrease in dihydroethidium (DHE) fluorescence, iron, malondialdehyde (MDA), and myeloperoxidase (MPO) were further observed in metformin-treated mice. In contrast, the damage to the GPX4/GSH system caused by IIRI was reversed after metformin treatment, as shown by increases in GPX4, SLC7A11, and GSH. The antiferroptotic effects of metformin were phenocopied by its fecal microbiota but were eliminated by antibiotic intake. 16S rRNA analysis revealed that the metformin-modulated gut microbiota was characterized by increased Lactobacillus murinus, which expressed higher levels of GshF that contributed to the mitigation of IIRI.</p><p><strong>Conclusions: </strong>Murine gut microbiota mediated the anti-ferroptotic effect of metformin on IIRI, and the resulting increase in microbial GSH synthesis could serve as a critical pathway for anti-IIRI.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"285"},"PeriodicalIF":7.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969661","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":"Exploring metabolomics for colorectal cancer risk prediction: evidence from the UK Biobank and ESTHER cohorts.","authors":"Teresa Seum, Rafael Cardoso, Joshua Stevenson-Hoare, Bernd Holleczek, Ben Schöttker, Michael Hoffmeister, Hermann Brenner","doi":"10.1186/s12916-025-04107-w","DOIUrl":"10.1186/s12916-025-04107-w","url":null,"abstract":"<p><strong>Background: </strong>While metabolic pathway alterations are linked to colorectal cancer (CRC), the predictive value of pre-diagnostic metabolomic profiling in CRC risk assessment remains to be clarified. This study evaluated the predictive performance of a metabolomics risk panel (MRP) both independently and in combination with established risk factors.</p><p><strong>Methods: </strong>We derived, internally validated (IV), and externally validated (EV) a metabolomics risk panel (MRP) for CRC from data of the UK Biobank (UKB) and the German ESTHER cohort. Baseline blood samples were assessed for 249 metabolites using nuclear magnetic resonance spectroscopy analysis. We applied LASSO Cox proportional hazards regression to identify metabolites for inclusion in the MRP and evaluated the model performance using the concordance index (C-index). We compared the performance of the MRP to an environmental risk panel (ERP; sex, age, body mass index, smoking status, and alcohol consumption) and a genetic risk panel (GRP; polygenic risk score).</p><p><strong>Results: </strong>The study included 154,892 participants of the UKB cohort (mean age at baseline 54.5 years; 55.5% female) with 1879 incident CRC and 3242 participants of the ESTHER cohort (mean age 61.5 years; 52.2% female) with 103 CRC cases. Twenty-three metabolites, primarily amino acid and lipid-related metabolites, were selected for the MRP, showing moderate predictive performance (C-index 0.60 [IV] and 0.54 [EV]). The ERP and GRP showed superior performance, with C-index values of 0.73 (IV) and 0.69 (EV). Adding the MRP to these risk models did not change the C-indices in both cohorts.</p><p><strong>Conclusions: </strong>Genetic and environmental risk information provided strong predictive accuracy for CRC risk, with no improvements from adding metabolomics data. These findings suggest that metabolomics data may have limited impact on enhancing established CRC risk models in clinical practice.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"283"},"PeriodicalIF":7.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985499","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":"Discovery and validation of a novel dual-target blood test for the detection of hepatocellular carcinoma across stages from cirrhosis.","authors":"Wenhao Teng, Hui Li, Hao Yang, Yu Chen, Liying Xi, Fuli Xin, Aiyuan Zhang, Lihui Yu, Lu Zheng, Ming Wang, Jian Bai, Fayong Ke, Yin Wang, Fuming Sun, Hui Zhang, Lin Wu, Jingfeng Liu","doi":"10.1186/s12916-025-04115-w","DOIUrl":"https://doi.org/10.1186/s12916-025-04115-w","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is one of the most common cancers. Early detection of HCC helps improve the patients' 5-year survival rate. Our goal was to identify superior methylation biomarkers to develop a methylation-specific quantitative PCR (MS‒qPCR) assay.</p><p><strong>Methods: </strong>A five-phase case-control study identified HCC methylation biomarkers via capture sequencing, TCGA/RNA-seq filtering, technical (MS-qPCR/Sanger) and biological (quadruplex MS-qPCR) validation. Methylated biomarkers were selected based on differential methylation expression using a tissue discovery cohort (43 HCC, 32 normal) and validated in plasma validation cohorts (Phase 1: 53 HCC, 52 cirrhosis, 20 benign, 50 healthy; Phase 2: 67 HCC, 81 cirrhosis). Then, the final assay's HCC detection performance was compared with existing blood-based surveillance methods.</p><p><strong>Results: </strong>Two methylated genes, OSR2 and TSPYL5, and a novel internal reference gene, SDF4, were identified and developed into an MS‒qPCR assay named Qliver. Qliver had an AUC of 0.955 (95% CI: 0.924-0.987) for distinguishing HCC patients from non-HCC patients in the Phase 1 plasma cohort, with a sensitivity of 88.68% (95% CI: 76.97%-95.73%) and a specificity of 89.34% (95% CI: 82.47%-94.20%), and 0.958 (95% CI: 0.927-0.989) for distinguishing HCC patients from cirrhosis patients in the Phase 2 plasma cohort, with a sensitivity of 88.06% (95% CI: 77.82%-94.70%) and a specificity of 92.59% (95% CI: 84.57%-97.23%). For the Phase 1 plus Plasma 2 cohort, Qliver had an AUC of at least 0.958 for detecting HCC in healthy individuals, cirrhosis patients and patients with benign liver diseases, which was superior to that of the GALAD score (AUC: 0.777 to 0.849). For BCLC stage 0 and A HCC patients, the sensitivity of Qliver ranged from 62.50% (95% CI: 24.49%-91.48%) to 72.73% (39.03%-93.98%), with a specificity of 90%. Overall, Qliver was superior to the AFP, AFP-L3, DCP and the GALAD score in terms of cirrhosis history, tumor stage, tumor size and tumor count.</p><p><strong>Conclusions: </strong>Qliver demonstrated superior performance in detecting HCC compared with currently widely used blood biomarkers, suggesting its potential clinical benefit in HCC surveillance in high-risk populations.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"278"},"PeriodicalIF":7.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976808","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":"Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy for locally advanced rectal cancer: 3-year survival from a phase 2 study.","authors":"Zhenyu Lin, Peng Zhang, Ming Cai, Gang Li, Tao Liu, Kailin Cai, Jing Wang, Junli Liu, Hongli Liu, Weikang Zhang, Jinbo Gao, Chuanqing Wu, Linfang Wang, Zheng Wang, Zhiguo Hou, Hongyi Kou, Kaixiong Tao, Tao Zhang","doi":"10.1186/s12916-025-04087-x","DOIUrl":"https://doi.org/10.1186/s12916-025-04087-x","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant short-course radiotherapy (SCRT) followed by camrelizumab and chemotherapy has shown an encouraging pathological complete response rate (48.1%, primary endpoint) in patients with locally advanced rectal cancer (LARC). Here, we present the 3-year survival outcomes.</p><p><strong>Methods: </strong>In this phase 2 trial, patients with previously untreated T3-4N0M0 or T1-4N + M0 rectal adenocarcinoma received 5 × 5 Gy SCRT over 5 days, followed by two cycles of camrelizumab (200 mg) and CAPOX regimen every 3 weeks after 1 week. Total mesorectal excision (TME) was scheduled 1 week after the completion of neoadjuvant treatment. The 3-year disease-free survival (DFS) and overall survival (OS) were evaluated in this analysis.</p><p><strong>Results: </strong>A total of 30 patients were enrolled, of whom 28 (93.3%) had microsatellite stable status (MSS) and 27 (90.0%) underwent TME. With a median follow-up of 40.8 months, the median DFS and OS were both not reached, with the 3-year DFS and OS rates of 80.2% (95% CI 58.6-91.3) and 93.3% (95% CI 75.9-98.3), respectively. Additionally, there was a trend toward improved 3-year DFS and OS in patients with pCR, postoperative pathological node-negative status (pN0), baseline negative circumferential resection margin as assessed by MRI, baseline negative extramural venous invasion and a PD-L1 combined positive score of 1 or higher, as compared with those without these characteristics.</p><p><strong>Conclusions: </strong>Our data support the potential efficacy of neoadjuvant SCRT followed by camrelizumab and CAPOX regimen in LARC, as indicated by 3-year survival outcomes, suggesting that this may be an alternative therapeutic strategy, especially with the potential to address an unmet need for MSS patients.</p><p><strong>Trial registration: </strong>www.</p><p><strong>Clinicaltrials: </strong>gov . NCT04231552.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"273"},"PeriodicalIF":7.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970699","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}