BMC Medicine最新文献

{"title":"Development and validation of a postpartum cardiovascular disease risk prediction model in women incorporating reproductive and pregnancy-related predictors.","authors":"Steven Wambua, Francesca L Crowe, Shakila Thangaratinam, Dermot O'Reilly, Colin McCowan, Sinead Brophy, Christopher Yau, Krishnarajah Nirantharakumar, Richard D Riley, Kym I E Snell","doi":"10.1186/s12916-025-04229-1","DOIUrl":"https://doi.org/10.1186/s12916-025-04229-1","url":null,"abstract":"<p><strong>Background: </strong>Each year, over 700,000 pregnancies occur in the UK, with up to 10% affected by complications such as hypertensive disorders of pregnancy and gestational diabetes mellitus. Pregnancy-related complications and reproductive factors are associated with an increased risk of cardiovascular disease (CVD) later in life. Our aim was to determine whether adding pregnancy factors to a prediction model with established CVD risk factors improves 10-year risk prediction of CVD in postpartum women, using QRISK®-3 as a benchmark model.</p><p><strong>Methods: </strong>We used a population-based retrospective cohort of women aged 15 to 49 who had been pregnant from the Clinical Practice Research Datalink (CPRD) primary care database. Women who were CVD-free were followed from 6 months postpartum. We evaluated the performance of QRISK®-3 and updated the risk prediction model using established risk factors for CVD from QRISK®-3 and additional risk factors specific to pregnancy. Models were developed using Cox-proportional hazards regression for CVD within 10 years. Models were evaluated and compared using measures of overall model fit, calibration, discrimination and clinical utility.</p><p><strong>Results: </strong>Among 567,667 eligible women, 2175 (0.38%) experienced a CVD event within 10 years. The median follow-up was 4 years. Of the additional pregnancy factors, gestational hypertension, preeclampsia, miscarriage, stillbirth, postnatal depression, gravidity, endometriosis and polycystic ovary syndrome remained associated with CVD after adjusting for other established risk factors of CVD. Adding pregnancy factors to those from QRISK®-3 led to marginal improvements in model performance (QRISK®-3 C-statistic: 0.703 (95% CI 0.687 to 0.718), updated model C-statistic: 0.726 (95% CI 0.711 to 0.740) Although calibration did not improve overall, subgroup analysis showed better calibration in women with a history of pre-eclampsia, postnatal depression and preterm birth using the updated model. The clinical utility was improved for updated models.</p><p><strong>Conclusions: </strong>The updated risk prediction models resulted in marginal improvement in discrimination and calibration compared to QRISK®-3 in postpartum women. This could be due to the known association of pregnancy-related complications with established risk factors of CVD. Although the overall predictive performance and calibration of the updated models was similar, the updated model resulted in better clinical utility.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"508"},"PeriodicalIF":8.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943299","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":"Accelerometer-derived \"weekend warrior\" physical activity pattern and cardiovascular disease in individuals with hypertension: a prospective cohort study.","authors":"Yanan Qiao, Hui Yang, Ruilang Lin, Yongfu Yu, Min Zhao, Bo Xi","doi":"10.1186/s12916-025-04344-z","DOIUrl":"https://doi.org/10.1186/s12916-025-04344-z","url":null,"abstract":"<p><strong>Background: </strong>Extensive evidence has demonstrated that physical activity (PA), particularly moderate-to-vigorous intensity PA (MVPA), has protective effects on cardiovascular disease (CVD) in individuals with hypertension. However, the relative effects of different PA patterns in this high-risk population remain unclear. We aimed to evaluate the associations of three PA patterns (\"weekend warrior\" (WW), regularly active, and inactive) with incident CVD in individuals with hypertension.</p><p><strong>Methods: </strong>This large prospective cohort study included 40,283 adults with hypertension from the UK Biobank who had accelerometer-measured PA data between June 2013 and December 2015. Participants were categorized into three groups: the regularly active pattern, the WW pattern, and the inactive group. Outcomes included overall CVD, as well as its four major subtypes: myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), and stroke. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between PA patterns and outcomes.</p><p><strong>Results: </strong>Over a median follow-up of 7.59 years (interquartile range, 7.33-8.47), 3789 new cases of overall CVD were identified. Compared with the inactive group, both the WW (HR = 0.76, 95% CI = 0.71-0.82) and regularly active (0.78, 0.71-0.85) patterns were associated with a significantly and similarly reduced risk of developing overall CVD. Moreover, both active groups showed reduced risks of incident MI (WW, 0.75, 0.65-0.87; regularly active, 0.72, 0.61-0.86), AF (WW, 0.77, 0.70-0.85; regularly active, 0.80, 0.71-0.90), HF (WW, 0.58, 0.50-0.68; regularly active, 0.67, 0.56-0.80), and stroke (WW, 0.78, 0.65-0.93; regularly active, 0.85, 0.70-1.05). Additional subgroup and sensitivity analyses confirmed the robustness of main findings.</p><p><strong>Conclusions: </strong>The WW pattern was associated with a similarly lower risk of CVD as more evenly distributed activity in individuals with hypertension, offering an effective and flexible strategy for improving cardiovascular health.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"506"},"PeriodicalIF":8.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943361","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":"Income-based inequalities in risk factors of NCDs and inequities of preventive care services amongst 202,682 adults: a cross-sectional study of South Asia Biobank.","authors":"Bernardo Andretti, Petya Atanasova, Zoey Verdun, Nalinda Tharanga Wellappuli, Rajendra Pradeepa, Sudha Vasudevan, Akansha Tyagi, Ali Ahsan, Md Mokbul Hossain, Abu Ahmed Shamim, Fahmida Akter, Sara Mahmood, Lathika Athauda, Manoja Gamage, Manuja Kaluarachchi, Thomas Burgoine, Soren Brage, Nita G Forouhi, Ian Goon, Marie Loh, Prasad Katulanda, Anuradhani Kasturiratne, Khadija Irfan Khawaja, Sajjad Ahmad, Malay K Mridha, Vinitaa Jha, Ranjit Mohan Anjana, John C Chambers, Gary Frost, Franco Sassi, Marisa Miraldo","doi":"10.1186/s12916-025-04308-3","DOIUrl":"https://doi.org/10.1186/s12916-025-04308-3","url":null,"abstract":"<p><strong>Background: </strong>There is scant research examining income-based inequalities in risk factors of non-communicable diseases (NCDs) and inequities of preventive care services across the South Asian population.</p><p><strong>Methods: </strong>We conducted a cross-sectional study of 202,682 adults aged 18 or above in four South Asian countries: Bangladesh, India, Pakistan, and Sri Lanka. We combined South Asia Biobank (SAB) surveillance data with environmental mapping exposure and 24-h dietary recall to estimate income-based inequalities using concentration curves and concentration indices (CI) that measure the magnitude and directional inequality effects. We also computed the horizontal inequity index (HII) for need-standardised healthcare utilisation and advice by measuring the extent to which the distribution of health promotion advice matches the distribution of diet-related risk factor variables across the income distribution. We reported concentration index coefficients and standard errors.</p><p><strong>Results: </strong>Inequalities in exposure and diet-related risk factors of NCDs were observed. Underweight was concentrated amongst the poor (CI = - 0.16, SE = 0.005, p < 0.001), while overweight and obesity were concentrated amongst the rich (CI = 0.11, SE = 0.003, p < 0.001). Non-recommended intake of fats (CI = 0.04, SE = 0.003, p < 0.001) and carbohydrates were concentrated amongst the rich (CI = 0.05, SE = 0.003, p < 0.001), while non-recommended intake of free sugars (CI = - 0.05, SE = 0.004, p < 0.001) and fruits and vegetables amongst the poor (CI = - 0.07, SE = 0.005, p < 0.001). Exposure to unhealthy outlets was concentrated amongst the rich (CI = 0.02, SE = 0.002, p < 0.001). There were persistent and pro-rich inequities in healthcare utilisation (HII = 0.02, SE = 0.002, p < 0.001) and advice for salt reduction (HII = 0.02, SE = 0.004, p < 0.001), fat reduction (HII = 0.02, SE = 0.004, p < 0.001), healthy weight (HII = 0.03, SE = 0.006, p < 0.001), and fruits and vegetables consumption (HII = 0.04, SE = 0.004, p < 0.001).</p><p><strong>Conclusions: </strong>These findings indicate the need to address and mitigate income-based inequalities in diet-related risk factors of NCDs and underscore the need of policies directed at mitigating NCDs risk exposure and achieving improved and equitable access to healthcare.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"504"},"PeriodicalIF":8.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942997","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":"The effect of fruit smoothie supplementation on psychological distress and biomarkers among people with opioid dependence receiving opioid agonist therapy: a randomized controlled trial.","authors":"Elaheh Javadi Arjmand, Lise Margrete Thomassen, Karl Trygve Druckrey-Fiskaaen, Einar Furulund, Jørn Henrik Vold, Tesfaye Madebo, Rune Blomhoff, Jan Tore Daltveit, Hege Berg Henriksen, Fatemeh Chalabianloo, Kjell Arne Johansen, Torgeir Gilje Lid, Lars Thore Fadnes","doi":"10.1186/s12916-025-04347-w","DOIUrl":"https://doi.org/10.1186/s12916-025-04347-w","url":null,"abstract":"<p><strong>Background: </strong>Unhealthy diets are common among individuals with opioid dependence. While fruit- and vegetable-rich diets have shown mental health benefits, evidence is limited for those receiving opioid agonist therapy (OAT). This trial evaluated the effectiveness of fruit smoothie supplementation for people receiving OAT compared to standard treatment without fruit smoothie supplementation.</p><p><strong>Methods: </strong>In this multicenter randomized controlled trial (FruktBAR), 311 participants receiving OAT were randomized (5:3 intervention:control) to receive either a daily 250 ml fruit smoothie for 16 weeks in addition to standard OAT or standard OAT alone. The primary outcome was the difference between the arms in changes in psychological distress, measured by the ten-item Hopkins Symptom Checklist (SCL-10%) from baseline to the end of the intervention. The secondary outcomes included changes in fatigue symptoms, measured using the three-item Fatigue Severity Scale, physical fitness, measured by a 4-min step test, carotenoid and folate biomarkers.</p><p><strong>Results: </strong>At baseline, 131 participants (70%) in the intervention arm and 91 (73%) in the control arm had a low intake of fruits and vegetables. In the intervention arm, the mean SCL-10% score at baseline was 43.9% (95% confidence interval (CI): 40.4, 47.4), which was reduced to 41.6% (CI: 38.0, 5.1) at the end of the trial. In the control arm, the mean SCL-10% score was 43.6% at baseline (CI: 39.3, 48.0) and decreased to 41.5% (CI: 37.1, 45.8) at the end of the trial period. No significant difference in the change of psychological distress between the intervention and control arms was found (- 0.14%; CI: - 4.49, 2.22). Additionally, no changes were found between the intervention and control arms regarding fatigue symptoms, physical fitness, carotenoid, or folate biomarkers. The mean consumed fruit smoothies reported in the intervention arm was 3.9 bottles per week (SD 1.5).  CONCLUSIONS: Fruit smoothie supplementation over a 16-week period did not impact psychological distress, fatigue, physical fitness, carotenoids, or folate biomarkers among people receiving OAT. Although the smoothies were successfully delivered to the participants, our data indicates suboptimal adherence to the intervention rather than the lack of efficacy.  TRIAL REGISTRATION: ClinicalTrials.gov NCT05229770. Registered on 08 February 2022.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"505"},"PeriodicalIF":8.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943161","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":"Whole genome transcriptional analysis of intestinal biopsies and blood cells indicate genes involved in antioxidant defense systems, amino acid metabolism and antigen presentation in the pathogenesis of celiac disease.","authors":"Åsa Torinsson Naluai, Shafir Sabbag, Sanna Abrahamsson, Audur H Gudjónsdóttir, Henrik Arnell, Daniel Agardh","doi":"10.1186/s12916-025-04261-1","DOIUrl":"https://doi.org/10.1186/s12916-025-04261-1","url":null,"abstract":"<p><strong>Background: </strong>Celiac disease is associated with HLA-risk haplotypes, but non-HLA genes and environmental factors are also linked to disease susceptibility. In this study, we explore the molecular pathways involved in celiac disease by analyzing the differential expression of genes in both the gut and peripheral blood across various celiac disease phenotypes.</p><p><strong>Methods: </strong>Whole genome RNA sequencing was performed on 283 samples from intestinal mucosa and peripheral blood from 72 cases with either active, potential, or treated celiac disease and 73 disease controls. Enrichr pathway analysis of top differentially expressed genes was performed.</p><p><strong>Results: </strong>Overall, 7565 genes in intestinal biopsies and 542 genes in blood samples were differentially expressed between cases and controls. Compared with controls, immunoglobulin heavy variable 5-51 (IGHV5-51) (p = 1.05 × 10^-14) and tissue transglutaminase (TGM2) (p = 5.29 × 10^-10), encoding for TG2, the main autoantigen in celiac disease, were two of the top up-regulated genes in intestinal biopsies from celiac cases. TGM2 was also slightly upregulated in blood cells from cases with active disease compared with controls (p = 0.05). The topmost differentially expressed genes in peripheral blood were HLA-DQB1, HLA-DQB2, and GSTM1. Among pathways identified containing transcriptionally differentiated genes were antioxidant defense systems (e.g., nuclear factor (erythroid-derived 2)-like 2 (Nrf2), glutathione, ergothioneine, and peroxisome metabolism), as well as MHC class 1 antigen presentation, amino acid transport, mTORC1, bilirubin and lipid metabolism, liver homeostasis, the complement system, and interferon signaling.</p><p><strong>Conclusions: </strong>Differentially expressed genes in cases and controls indicate crosstalk between molecular pathways involved in antioxidant defense, immune regulation, and nutrient signaling in the pathogenesis of celiac disease.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"507"},"PeriodicalIF":8.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943179","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":"Effects of Mediterranean diet, exercise, and their combination on body composition and liver outcomes in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials.","authors":"Vicente Artola Arita, Manuel Castro Cabezas, Juliana Alexandra Hernández Vargas, Silvia Juliana Trujillo-Cáceres, Nathalie Mendez Pernicone, Lara Anne Bridge, Hamidreza Raeisi-Dehkordi, Carmen A W Dietvorst, Ruben Dekker, Julieth Pilar Uriza-Pinzón, Mohamed Tawfik, Kirsten A Berk, Jo Massoels, Stan Driessen, Maarten E Tushuizen, Adriaan G Holleboom, Diederick E Grobbee, Oscar H Franco, Sara Beigrezaei","doi":"10.1186/s12916-025-04320-7","DOIUrl":"https://doi.org/10.1186/s12916-025-04320-7","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of liver-related morbidity and mortality. Lifestyle interventions like the Mediterranean diet (MD) and exercise are recommended for management, but the most effective lifestyle approach remains unclear.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted in Embase, MEDLINE via Ovid, Cochrane Central, and Web of Science Core Collection from inception to April 1, 2025, without language restrictions. We included randomized controlled trials (RCTs) in adults with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) assessing the MD and/or exercise interventions on anthropometric measures, liver enzymes, and indices or grades of liver steatosis and fibrosis. The mean difference and corresponding 95% confidence interval (CI) were pooled using a random-effects model. Risk of bias was assessed with ROB-2, and evidence certainty was evaluated using GRADE.</p><p><strong>Results: </strong>From a total of 4806 search results, 37 unique RCTs met the inclusion criteria, from which 11 assessed the MD and 27 exercise, either aerobic, resistance, or in combination, and two RCTs assessed the effect of the MD and exercise combination. Meta-analyses showed that the MD in comparison with the control significantly reduced body weight [weighted mean difference (WMD = - 2.38 kg, 95% CI - 4.11 to - 0.66), body mass index (WMD = - 0.70 kg/m², 95% CI = - 1.03 to - 0.36), waist circumference (WC) (WMD = - 1.56 cm, 95% CI - 3.02 to - 0.09), and alanine aminotransferase (ALT) (WMD = - 3.96 IU/L, 95% CI - 6.54 to - 1.38). Aerobic and combined aerobic-resistance exercises in comparison with the control group reduced body weight (WMD = - 1.56 kg, 95%CI - 2.31 to - 0.82; WMD = - 1.90 kg, 95%CI - 3.59 to - 0.22, respectively). In addition, aerobic exercise significantly decreased WC (WMD = - 2.14 IU/L, 95%CI - 2.87 to - 1.41) and resistance exercise reduced ALT (WMD = - 15.40 IU/L, 95%CI - 28.60 to - 2.20) in patients with MASLD/MASH compared to the control group.</p><p><strong>Conclusions: </strong>The MD and aerobic exercise, whether alone or combined with resistance training, support weight loss and improve liver health in patients with MASLD/MASH. Standardized methods for measuring and reporting outcomes are essential to build robust evidence on the impact of lifestyle changes on clinical outcomes. TRIAL REGISTRATION: PROSPERO registration code. CRD42024577846.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"502"},"PeriodicalIF":8.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943334","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":"Risk stratification and outcomes in diabetes mellitus patients with preserved ejection fraction: a cardiac MRI study.","authors":"Wenjing Yang, Mengdi Jiang, Huaying Zhang, Di Zhou, Yining Wang, Leyi Zhu, Zhaoxin Tian, Gang Yin, Qiang Zhang, Arlene Sirajuddin, Andrew E Arai, Shihua Zhao, Minjie Lu","doi":"10.1186/s12916-025-04354-x","DOIUrl":"https://doi.org/10.1186/s12916-025-04354-x","url":null,"abstract":"<p><strong>Background: </strong>Patients with diabetes mellitus (DM) have a significantly increased risk of developing heart failure (HF), which exacerbates adverse cardiovascular outcomes. Limited data are available on the prognostic value of cardiac MRI in DM. We aimed to evaluate the association between MRI-derived strain analysis and adverse outcomes in DM patients at different heart failure (HF) stages.</p><p><strong>Methods: </strong>In this prospective study, DM participants with preserved ejection fraction (EF) underwent MRI examination between January 2019 and December 2021 were evaluated. Feature tracking strain parameters were measured using cine MRI. The primary outcome was a composite outcome including HF hospitalization or cardiovascular death. Cox proportional regression was used to assess the association between risk factors and outcomes.</p><p><strong>Results: </strong>A total of 581 DM participants (mean age, 56 years ± 13; 401 men) including 390 asymptomatic patients (stage A/B HF) and 191 heart failure with preserved EF were evaluated. After a median follow-up of 34.3 months, 74 DM patients reached the primary outcome; 13(2.2%) had cardiovascular mortality and 61(10.5%) had heart failure hospitalization. Kaplan-Meier survival curves showed that patients with global longitudinal strain (GLS) greater than or equal to -13.76% and patients with global early diastolic longitudinal strain rate (eGLSR) less than or equal to 0.51/s were more likely to experience the primary outcome (log-rank P < 0.001). In multivariable analysis, eGLSR was independently associated with an increased risk of the primary endpoint(per SD, adjusted HR: 2.038; 95% CI: 1.384-3.002; P < 0.001), but GLS was not. When risk stratification was based on GLS and eGLSR, Kaplan-Meier survival curves showed that patients with abnormal eGLSR had a significantly higher risk of adverse outcomes, regardless of GLS status. In addition, eGLSR provided incremental predictive power over clinical and imaging variables, achieving the largest C-statistic of 0.744. Of note, the association between eGLSR and outcomes was consistent in stage A/B HF patients and patients with HFpEF. Subgroup analysis showed non-ischemic LGE assessed by MRI was also independently associated with outcomes in patients with DM.</p><p><strong>Conclusions: </strong>In DM patients with preserved ejection fraction, left ventricular eGLSR measured by cardiac MRI was an independent predictor of adverse outcomes and offered incremental prognostic value over conventional clinical and imaging indices.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"500"},"PeriodicalIF":8.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943100","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":"Extracellular vesicle-derived lncRNA-GC1 serves as a novel biomarker for predicting and monitoring the immunotherapeutic outcomes of patients with gastric cancer.","authors":"Jiangpeng Wei, Xinxin Wang, Danhong Dong, Yi Ru, Lubin Chen, Xin Cheng, Xiaohui Lv, Xin Guo","doi":"10.1186/s12916-025-04270-0","DOIUrl":"https://doi.org/10.1186/s12916-025-04270-0","url":null,"abstract":"<p><strong>Background: </strong>Efforts to predict the outcomes of patients with gastric cancer (GC) following immune checkpoint inhibitor (ICI) treatments remain limited, owing to a lack of reliable biomarkers. Studies have found that extracellular vesicle (EV)-derived lncRNA-GC1 may serve as a GC-specific biomarker. This study was designed to expand on these previous results by estimating the usefulness of EV-derived lncRNA-GC1 as a predictive indicator for patients with GC who undergo ICI treatments.</p><p><strong>Methods: </strong>EV-derived lncRNA-GC1 levels were measured using real-time polymerase chain reaction (RT-PCR) in patients with unresectable or metastatic GC who were receiving ICI treatments. Correlations between this biomarker and ICI treatment outcomes were analyzed in a training cohort (n = 136), two external validation cohorts (n = 188 and n = 214), one expanding cohort (n = 30), and one prospective cohort (n = 192).</p><p><strong>Results: </strong>Circulating EVs exhibited a lncRNA-GC1 expression profile that was distinct from that of tissues or circulating cells. EV-derived lncRNA-GC1 levels were found to be independent of PD-L1 expression status or the density of CD8⁺ T cell infiltration. EV-derived lncRNA-GC1 could be used to effectively predict ICI-related patient outcomes, and could be used for dynamic monitoring throughout treatments. Lower levels of EV-derived lncRNA-GC1 were associated with tumor microenvironmental characteristics such as more robust antitumor immunity-including higher levels of activated CD8⁺ T/NK cells and an increased TH1/TH2 ratio. Such biomarkers can be stably detected in clinical practice. These results were consistent in both the two external validation cohorts and the one prospective cohort.</p><p><strong>Conclusions: </strong>EV-derived lncRNA-GC1 can be used to reliably predict immunotherapeutic outcomes in patients with GC who undergo ICI treatments, suggesting that targeted analyses of this lncRNA may be useful for guiding treatment planning, monitoring, and associated decision-making processes.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"499"},"PeriodicalIF":8.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943341","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":"Pharmacokinetics, safety, and efficacy of mixed formulation of fosrolapitant and palonosetron (HR20013) in combination with dexamethasone in patients with solid tumors scheduled for highly emetogenic cisplatin-based chemotherapy: a phase I trial.","authors":"Yuanyuan Zhao, Yuxiang Ma, Tengrui Yin, Zhiquan Qin, Linlin Liu, Guoqiang Kong, Ranran Zhang, Yuanyuan Huang, Li Zhang, Hongyun Zhao","doi":"10.1186/s12916-025-04314-5","DOIUrl":"10.1186/s12916-025-04314-5","url":null,"abstract":"<p><strong>Background: </strong>This phase I trial aimed to assess the pharmacokinetics (PK), safety, and preliminary efficacy of a single dose of HR20013 (mixed formulation of fosrolapitant and palonosetron) plus dexamethasone in patients with malignant solid tumors.</p><p><strong>Methods: </strong>Solid tumor patients who were naive to cisplatin-based chemotherapy and scheduled to receive the single-day cisplatin-based chemotherapy were enrolled. Patients would receive a single intravenous infusion of HR20013 (Day 1) before cisplatin-based chemotherapy, alongside oral dexamethasone (Day 1, 12 mg, once a day; Day 2-4, 3.75 mg, twice a day). Primary endpoints were PK parameters of fosrolapitant, rolapitant, M19 (a major active metabolite of rolapitant), palonosetron, and dexamethasone.</p><p><strong>Results: </strong>Twenty-four patients were enrolled, and 22 received study treatment. Fosrolapitant reached maximum plasma concentration (C_max) immediately at the end of the infusion of HR20013 (1 h), followed by a short terminal phase, and it was completely hydrolyzed into rolapitant. Mean elimination half-lives of rolapitant and palonosetron were 188.2 and 51.5 h, respectively. M19 reached C_max at approximately 166.2 h. After a single oral administration of dexamethasone at 12 mg, when combined with HR20013, dexamethasone reached C_max at approximately 1.5 h, with a mean C_max of 106.0 ng/mL. Treatment-related adverse events occurred in 54.5% of patients, with constipation (22.7%), increased blood pressure (18.2%), abdominal distension (13.6%), injection site reaction (9.1%), and increased neutrophil count (9.1%) being most common. Complete response rates (no emesis/rescue therapy) were 90.9% at the overall phase (0-120 h) and 86.4% at the beyond delayed phase (120-168 h).</p><p><strong>Conclusions: </strong>HR20013 plus dexamethasone had a favorable PK profile, manageable safety, and durable antiemetic efficacy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT05465681.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"501"},"PeriodicalIF":8.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943046","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":"External validation of the COLOFIT colorectal cancer risk prediction model in the Oxford-FIT dataset: the importance of population characteristics and clinically relevant evaluation metrics.","authors":"Andres Tamm, Brian Shine, Tim James, Jaimie Withers, Hizni Salih, Theresa Noble, Kinga A Várnai, James E East, Gary Abel, Willie Hamilton, Colin Rees, Eva J A Morris, Jim Davies, Brian D Nicholson","doi":"10.1186/s12916-025-04339-w","DOIUrl":"https://doi.org/10.1186/s12916-025-04339-w","url":null,"abstract":"<p><strong>Background: </strong>A faecal immunochemical test (FIT) result ≥ 10 µg/g is recommended in the UK to triage patients with symptoms of colorectal cancer (CRC) in primary care for urgent cancer investigation. The COLOFIT model combining FIT results with demographics and blood tests was developed to reduce the proportion of people referred without CRC. This study aims to externally validate the COLOFIT using data from Oxford University Hospitals (OUH).</p><p><strong>Methods: </strong>FITs requested by GPs between January 2017 and February 2024 were extracted from the OUH Clinical Data warehouse. Adults with COLOFIT predictors and 180-day follow-up for CRC were included. External validation of the COLOFIT equation was conducted overall and for six independent time periods. Risk score thresholds where the model captured the same number of cancers as FIT ≥ 10 µg/g were estimated to understand the number of urgent referrals avoided.</p><p><strong>Results: </strong>A total of 51,477 individuals (659 CRC) were included; 6194 (12%) had FIT ≥ 10 µg/g. FIT positivity and testing volume increased over time, associated with a gradual change from testing lower-risk patients to including those with higher-risk symptoms. COLOFIT was poorly calibrated overall (observed/expected [O/E] ratio 1.52 with calibration slope 1.05), but calibration improved over time (up to O/E ratio 1.09 with calibration slope 1.05). COLOFIT reduced referrals by 8% overall without missing colorectal cancers compared to FIT ≥ 10 µg/g, but this varied from 23% reduction to 2% increase depending on the period evaluated.</p><p><strong>Conclusions: </strong>The potential benefit of COLOFIT varied depending on FIT testing rates, the proportion of FIT ≥ 10 µg/g, and the symptoms in the tested population. Adopting COLOFIT into current clinical practice demands, therefore, FIT positivity of at least 17% and CRC rates within 1.3-1.6%. Further validation in local and different populations would also be of significant value and help to maximise COLOFIT's ability to improve diagnostic pathways.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"503"},"PeriodicalIF":8.3,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943352","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}