BMC Medicine最新文献

{"title":"Microbiota boost immunotherapy? A meta-analysis dives into fecal microbiota transplantation and immune checkpoint inhibitors.","authors":"Anqi Lin, Lihaoyun Huang, Aimin Jiang, Lingxuan Zhu, Weiming Mou, Yu Li, Chunyan Zhang, Zaoqu Liu, Jian Zhang, Quan Cheng, Ting Wei, Peng Luo","doi":"10.1186/s12916-025-04183-y","DOIUrl":"10.1186/s12916-025-04183-y","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) are a cornerstone of modern cancer treatment, but their effectiveness is limited. Fecal microbiota transplantation (FMT), which alters the gut microbiome, has shown promise in enhancing ICIs' therapeutic effects.</p><p><strong>Methods: </strong>We conducted a comprehensive search of relevant studies available up to September 30, 2024, to analyze the clinical efficacy and safety of combining FMT with ICIs in cancer treatment. The primary endpoint was the objective response rate (ORR), with secondary evaluations of survival outcomes and safety.</p><p><strong>Results: </strong>A total of 10 studies involving 164 patients with solid tumors were included. The pooled ORR was 43% (95% CI: 0.35-0.51). Subgroup analysis revealed that the combination of anti-PD-1 and anti-CTLA-4 therapies was associated with a significantly higher ORR (60%) compared to anti-PD-1 monotherapy (37%; P = 0.01). The incidence of grade 1-2 adverse events (AEs) was 42% (95% CI: 0.32-0.52), while grade 3-4 AEs occurred in 37% of patients (95% CI: 0.28-0.46).</p><p><strong>Conclusions: </strong>This meta-analysis provides preliminary evidence supporting the use of FMT as a strategy to enhance the efficacy of ICIs in patients with advanced or refractory solid tumors. However, larger-scale randomized controlled trials with long-term follow-up are required to confirm and optimize treatment protocols.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"341"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246458","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":"Artificial intelligence-assisted diagnosis and prognostication in low ejection fraction using electrocardiograms in inpatient department: a pragmatic randomized controlled trial.","authors":"Dung-Jang Tsai, Chin Lin, Wei-Ting Liu, Chiao-Chin Lee, Chiao-Hsiang Chang, Wen-Yu Lin, Yu-Lan Liu, Da-Wei Chang, Ping-Hsuan Hsieh, Chien-Sung Tsai, Yuan-Hao Chen, Yi-Jen Hung, Chin-Sheng Lin","doi":"10.1186/s12916-025-04190-z","DOIUrl":"10.1186/s12916-025-04190-z","url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis of low ejection fraction (EF) remains challenging despite being a treatable condition. This study aimed to evaluate the effectiveness of an electrocardiogram (ECG)-based artificial intelligence (AI)-assisted clinical decision support tool in improving the early diagnosis of low EF among inpatient patients under non-cardiologist care.</p><p><strong>Methods: </strong>We conducted a pragmatic randomized controlled trial at an academic medical center in Taiwan. 13,631 inpatient patients were randomized to either the intervention group (n = 6,840) receiving AI-generated ECG results or the control group (n = 6,791) following standard care. The primary outcome was the incidence of newly diagnosed low EF (≤ 50%) within 30 days following the ECG. Secondary outcomes included echocardiogram utilization rates, positive predictive value for low EF detection, and cardiology consultation rates. Statistical analysis included hazard ratios (HR) with 95% confidence intervals (CI) for time-to-event outcomes and chi-square tests for categorical variables.</p><p><strong>Results: </strong>The intervention significantly increased the detection of newly diagnosed low EF in the overall cohort (1.5% vs. 1.1%, HR 1.50, 95% CI: 1.11-2.03, P = 0.023), with a more pronounced effect among AI-identified high-risk patients (13.0% vs. 8.9%, HR 1.55, 95% CI: 1.08-2.21). While overall echocardiogram utilization remained similar between groups (17.1% vs. 17.3%, HR 1.00, 95% CI: 0.92-1.09), the intervention group demonstrated higher positive predictive value for identifying low EF among patients receiving echocardiogram (34.2% vs. 20.2%, p < 0.001). Post-hoc analysis revealed increased cardiology consultation rates among high-risk patients in the intervention group (29.3% vs. 23.5%, p = 0.027).</p><p><strong>Conclusions: </strong>Implementation of an AI-ECG algorithm enhanced the early diagnosis of low EF in the inpatient setting, primarily by improving diagnostic efficiency rather than increasing overall healthcare utilization. The tool was particularly effective in identifying high-risk patients who benefited from increased specialist consultation and more targeted diagnostic testing.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT05117970.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"342"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246454","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":"Projected health and economic effects of nonavalent versus bivalent human papillomavirus vaccination in preadolescence in the Netherlands.","authors":"Birgit Sollie, Johannes Berkhof, Johannes A Bogaards","doi":"10.1186/s12916-025-04170-3","DOIUrl":"10.1186/s12916-025-04170-3","url":null,"abstract":"<p><strong>Background: </strong>Most European countries offer human papillomavirus (HPV) vaccination through organised immunisation programmes, but the choice of vaccine varies. We compared the expected health and economic effects of the currently used bivalent vaccine, targeting HPV-16/18, and the nonavalent vaccine, targeting seven additional genotypes, for the Netherlands.</p><p><strong>Methods: </strong>We estimated the incremental impact of nonavalent versus bivalent vaccination in a cohort of 100,000 girls and 100,000 boys offered vaccination at age 10, by projecting type-specific infection risk reductions onto expected number of cervical screening outcomes, HPV-related cancers, and treatments for anogenital warts and recurrent respiratory papillomatosis (RRP). In the base-case, we assumed two-dose vaccination with 60% uptake, lifelong partial cross-protection against HPV-31/33/45 for the bivalent vaccine and EUR 25 extra cost per dose for the nonavalent vaccine. Cost-effectiveness was assessed from a healthcare provider perspective by comparing the incremental cost-effectiveness ratio (ICER) per life-year gained (LYG) with the Dutch threshold of EUR 20,000/LYG.</p><p><strong>Results: </strong>Compared with bivalent vaccination, nonavalent vaccination prevents an additional 1320 high-grade cervical lesions, 70 cancers, 34,000 anogenital warts episodes and 30 RRPs and generates EUR 4.1 million discounted savings from fewer treatments. The ICER is EUR 5489 (95% credible interval: 3765; 7019)/LYG in the base-case and exceeds the cost-effectiveness threshold only if the cross-protection for the bivalent vaccine extends permanently to non-31/33/45 genotypes or if the vaccine efficacy wanes past age 20 for both vaccines.</p><p><strong>Conclusions: </strong>Sex-neutral vaccination with the nonavalent vaccine is likely to be cost-effective. Long-term monitoring of type-specific vaccine effectiveness is essential because of the impact of cross-protection and waning efficacy on cost-effectiveness.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"339"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246460","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":"Fusion analysis of sMRI-DTI in patients with ulcerative colitis by multimodal CCA + joint ICA and associated neurotransmitter profiles.","authors":"Chengxiang Liu, Zi Wei, Jian Tang, Yintao Liu, Jingdong Lu, Yujia Li, Xin Liu, Peng Liu, Fenrong Chen","doi":"10.1186/s12916-025-04179-8","DOIUrl":"10.1186/s12916-025-04179-8","url":null,"abstract":"<p><strong>Background: </strong>As a chronic inflammatory disease, ulcerative colitis (UC) is characterized by complex etiology and unclear pathological mechanisms. Neuroimaging research plays a pivotal role in improving diagnostic accuracy and guiding treatment decisions, while enhancing our understanding of disease mechanisms. We aimed to explore the possible associations between gray matter volume (GMV) and white matter fractional anisotropy (FA) abnormalities as well as the neurotransmitter profiles in UC patients.</p><p><strong>Methods: </strong>Thirty-four UC patients and 21 healthy controls (HCs) participated in structural magnetic resonance imaging and diffusion tensor imaging scans. To identify the joint and specific independent components (ICs) across modalities between groups, multimodal canonical correlation analysis with joint independent component analysis was used for fusion analysis. ICs with significant group differences from the same index across two modalities were considered joint group-discriminative ICs. Joint ICs reveal cross-modal neurophysiological mechanisms of GMV-FA. A modal-specific group-discriminative IC is defined as a component that shows significant group difference only in unimodal, revealing specific neurophysiological mechanisms of GMV/FA. The relationship between neuroimaging findings and clinical characteristics was assessed. We also investigated the spatial correlations between the joint and modality-specific ICs and neurotransmitter profiles.</p><p><strong>Results: </strong>Compared to HCs, patients with UC showed one joint group-discriminating component (GMV_IC4-FA_IC4) mainly in the default mode network, thalamus, corpus callosum, corona radiata, fornix, posterior thalamic radiation, middle cerebellar peduncle, and corticospinal tract as well as one modality-specific group-discriminating component (FA_IC5). The loadings of GMV_IC5 were significantly negatively correlated with platelet levels in UC. Moreover, significant associations between the abnormalities of GMV_IC4 and the dopamine and gamma-aminobutric acid (GABAa) system, between the abnormalities of FA_IC4 and the dopamine, GABAa, acetylcholine, and glutamate system, and between the abnormalities of FA_IC5 and dopamine and serotonin systems were found in this study.</p><p><strong>Conclusions: </strong>This study suggested the complex interplay between structural alterations and associated neurotransmitter changes in neural systems subserving emotion dysregulation and visceral sensory processing in UC patients. The identified covarying GMV-FA complements previous findings of structural abnormalities. Furthermore, these findings provided novel insights into the neuropathological mechanisms and potential therapeutic targets of UC.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"345"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257385","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 impact of GnRH agonists on endometrial immune cells in patients with adenomyosis: a prospective cohort study.","authors":"Anna Lena Zippl, Christiana Kyvelidou, Monika Frank, Elisa Gapp, Elisabeth Reiser, Anne-Sophie Braun, Katharina Feil, Stefanie Schuchter, Patrick Rockenschaub, Bettina Toth, Beata Seeber","doi":"10.1186/s12916-025-04162-3","DOIUrl":"10.1186/s12916-025-04162-3","url":null,"abstract":"<p><strong>Background: </strong>Adenomyosis is associated with lower implantation and higher miscarriage rates. Studies on recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) have shown that endometrial immune cell populations play a crucial role during implantation and early pregnancy. In women with adenomyosis, improved pregnancy outcomes following assisted reproductive technologies (ART) and pre-treatment with GnRH-agonists (GnRH-a) prior to frozen embryo transfer (FET) have been reported. We aimed to compare the endometrial immune cell populations of women with adenomyosis to those of women with RPL and RIF, and to characterise endometrial leucocyte subpopulations within the adenomyosis group before and after GnRH-a.</p><p><strong>Methods: </strong>We conducted a prospective study between 2021 and 2024. Women with infertility and adenomyosis undergoing ART underwent one endometrial biopsy 6-9 days after oocyte retrieval and a second biopsy after 3 months of GnRH-a prior to FET. Women in the RPL and RIF groups underwent one endometrial biopsy in the midluteal phase. We performed flow cytometry (FC) to characterise immune cell populations and immunohistochemistry (IHC) to analyse uterine natural killer cells (uNKs) and plasma cells (PC). The Kruskal-Wallis test was used for comparisons between the study groups, and the Wilcoxon signed rank tests were used for paired samples before and after GnRH-a.</p><p><strong>Results: </strong>Endometrial leucocyte subpopulations at baseline showed no significant differences between the adenomyosis (n = 20), the RPL (n = 40) and RIF (n = 15) group. In the adenomyosis group, following GnRH-a, we observed a significant decrease in the percentage of monocytes, from 77% (IQR 71, 82) to 71% (IQR 65, 75) (adj. p = 0.030). Baseline IHC showed elevated plasma cell concentrations (≥ 5/mm²) in 1/20 adenomyosis patients (5%), 4/40 RPL patients (10%) and 1/15 RIF patients (6.7%) while uNK cells were elevated (≥ 300/mm²) in 8/20 adenomyosis patients (40%), 11/40 RPL patients (27.5%) and 1/15 RIF patients (6.7%).</p><p><strong>Conclusions: </strong>Women with infertility and adenomyosis showed a similar endometrial immune profile as women with RPL and RIF. The beneficial effect of GnRH-a prior to FET in women with adenomyosis may be mediated through effects on monocyte subpopulations. Based on the high prevalence of elevated uNK cells in patients with adenomyosis, we suggest testing women with adenomyosis undergoing ART before FET.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"338"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246386","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":"Platelets in preeclampsia: an observational study of indices associated with aspirin nonresponsiveness, activation and transcriptional landscape.","authors":"Gashaw Garedew Woldeamanuel, Kenean Getaneh Tlaye, Xueqin Wang, Long Nguyen-Hoang, Qiongjie Zhou, Yinan Wang, Bo Wah Leung, Yao Wang, Liona C Poon, Chi Chiu Wang","doi":"10.1186/s12916-025-04132-9","DOIUrl":"10.1186/s12916-025-04132-9","url":null,"abstract":"<p><strong>Background: </strong>Platelets play critical roles in the pathogenesis of preeclampsia, including thrombosis, endothelial dysfunction and inflammation. However, preeclampsia-associated changes in platelet gene expression and activation at the maternal-foetal interface remain unknown. Moreover, aspirin nonresponsiveness in high-risk pregnancies underscores the need for low-cost biomarkers to identify nonresponders. Nevertheless, the changes of platelet indices in women who develop preeclampsia despite aspirin prophylaxis have not yet been evaluated. In this study, we aimed to investigate the changes in platelet indices associated with aspirin nonresponsiveness, activation state and transcriptional landscape in preeclampsia.</p><p><strong>Methods: </strong>Platelet indices were compared between aspirin-responsive and nonresponsive women. Logistic regression analysis was performed to determine the associations between platelet indices and aspirin nonresponsiveness. Opal immunofluorescence staining was performed to evaluate the expression of platelet-specific (CD42b) and activation (CD62P) markers in placental villous and decidual tissues. RNA sequencing (RNA-seq) was performed to investigate the transcriptomic profile of platelets.</p><p><strong>Results: </strong>A decrease in platelet count (PC) during the second trimester as well as an increase in mean platelet volume (MPV) and a lower PC/MPV ratio in the third trimester were significantly associated with the subsequent development of aspirin nonresponsiveness. We observed significantly greater expression of CD62P in the placental villous and CD42b in the decidua of the preeclamptic group than in those of the nonpreeclamptic group. Colocalization analysis of CD42b and CD62P revealed that the preeclamptic placenta and decidua presented significant platelet activation. RNA-seq analysis revealed a total of 20, 618 and 1819 transcripts in the peripheral blood, placental villous and decidua of preeclamptic women, respectively. Functional analysis revealed that the PI3K-Akt and Wnt signalling pathways were significantly enriched in the placental villous and decidua of preeclamptic patients, respectively. RT‒qPCR analysis confirmed the upregulation of FKBP5, LAMA5, FZD5 and FGG mRNA expression in preeclampsia.</p><p><strong>Conclusions: </strong>Our findings suggest that PC in the second trimester and PC, MPV and PC/MPV ratio in the third trimester may be useful for assessing aspirin nonresponsiveness in women at high risk of preeclampsia. Furthermore, our findings demonstrate that preeclampsia is associated with increased platelet activation and significant enrichment of signalling pathways involved in platelet activation.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"346"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257386","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":"Short-term mortality after opioid initiation among opioid-naïve and non-naïve patients with dementia: a retrospective cohort study.","authors":"Yeon-Mi Hwang, Jennifer M Hah, Jennifer E Bramen, Jennifer J Hadlock, Tina Hernandez-Boussard","doi":"10.1186/s12916-025-04172-1","DOIUrl":"10.1186/s12916-025-04172-1","url":null,"abstract":"<p><strong>Background: </strong>In the ongoing opioid epidemic, the mortality risk of opioid initiation in patients with dementia or mild cognitive impairment (MCI) remains understudied despite their vulnerability. This study evaluates mortality risks associated with opioid exposure in patients diagnosed with dementia or MCI by comparing outcomes between the initiation and continuation groups.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using data from a Northern California academic healthcare system (Stanford Health Care Alliance; 2015/01/01-2024/07/31), including 27,757 patients aged 50-100 with dementia or MCI. Of these, 14,105 received opioids after diagnosis and were classified as initiation (opioid-naïve; n=9443) or continuation (non-naïve; n=4662) groups. Cox regression assessed 14-day mortality risk. Aalen's additive model examined time-varying impact up to 180 days. Potential causes of death were extracted from clinical notes using GPT-3.5-Turbo. We also analyzed an independent community healthcare system cohort (Providence Health & Service; n=208,306) from western US states (2015/01/01-2023/05/31) as a replication cohort.</p><p><strong>Results: </strong>In the primary cohort, 4.1% (572/14,105) of patients died within 14 days of opioid exposure. The initiation group had a significantly higher 14-day mortality risk than the continuation group (adjusted hazard ratio (aHR), 2.00 (1.59-2.52); P<0.0001). The replication cohort had a 14-day mortality rate of 6.2% (7022/113,343) with a smaller difference between the initiation (n=77,168) and continuation (n=36,175) groups (aHR 1.22 (1.16-1.30); P<0.0001). In both cohorts, elevated risk stabilized after day 30. In the primary cohort, respiratory conditions (62% vs. 48%, P<0.1), particularly pneumonia (38% vs. 19%, P<0.05), were more prevalent among the initiation group who died early.</p><p><strong>Conclusions: </strong>Starting opioids in patients with dementia or MCI is associated with elevated short-term mortality risks, with the initiation group having twice the 14-day mortality risk in academic settings and a smaller but significant increase in community healthcare systems. The first 30 days after initiation represent a critical risk window, likely due to a lack of tolerance to opioid adverse effects. These findings underscore the need for cautious initiation, tailored follow-up protocols accounting for healthcare setting characteristics, and close monitoring during the first month in this vulnerable population.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"340"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246385","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":"Nut consumption, linoleic and α-linolenic acid intakes, and genetics: how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in EPIC-InterAct and PREDIMED studies.","authors":"Susanne Jäger, Olga Kuxhaus, Marcela Prada, Inge Huybrechts, Tammy Y N Tong, Nita G Forouhi, Cristina Razquin, Dolores Corella, Miguel A Martinez-Gonzalez, Christina C Dahm, Daniel B Ibsen, Anne Tjønneland, Jytte Halkjær, Chloé Marques, Claire Cadeau, Xuan Ren, Verena Katzke, Benedetta Bendinelli, Claudia Agnoli, Alberto Catalano, Marta Farràs, Maria-Jose Sánchez, María Dolores Chirlaque López, Marcela Guevara, Dagfinn Aune, Stephen J Sharp, Nicholas J Wareham, Matthias B Schulze","doi":"10.1186/s12916-025-04187-8","DOIUrl":"10.1186/s12916-025-04187-8","url":null,"abstract":"<p><strong>Background: </strong>Dietary guidelines recommend replacing saturated fatty acid with unsaturated fats, particularly polyunsaturated fatty acids. Cohort studies do not suggest a clear benefit of higher intake of polyunsaturated fatty acids but, in contrast, higher circulating linoleic acid (LA) levels-reflective of dietary LA intake, are associated with a reduced risk of type 2 diabetes. However, genetic variants in the fatty acid desaturase 1 gene (FADS1) may influence individual responses to plant-based fats. We explored whether FADS1 variants influence the relationships of LA and α-linolenic acid (ALA) intakes and nut consumption with plasma phospholipid fatty acid profiles and type 2 diabetes risk in a large-scale cohort study and a randomized controlled trial.</p><p><strong>Methods: </strong>In the EPIC-InterAct case-cohort (7,498 type 2 diabetes cases, 10,087 subcohort participants), we investigated interactions of dietary and plasma phospholipid fatty acids and nut consumption with FADS1 rs174547 in relation to incident type 2 diabetes using weighted Cox regression. In PREDIMED (492 participants in the Mediterranean Diet + Nuts intervention group, 436 participants in the control group), we compared changes in plasma phospholipid FAs from baseline to year 1.</p><p><strong>Results: </strong>In EPIC-InterAct and PREDIMED, nut consumption was positively associated with LA plasma levels and inversely with arachidonic acid, the latter becoming stronger with increasing number of the minor rs174547 C allele (p interaction EPIC-InterAct: 0.030, PREDIMED: 0.003). Although the inverse association of nut consumption with diabetes seemed stronger in participants with rs174547 CC-genotype (HR: 0.73, 95% CI: 0.54-1.00) compared with CT (0.94, 0.81-1.10) or TT (0.90, 0.78-1.05) in EPIC-InterAct, this interaction was not statistically significant.</p><p><strong>Conclusions: </strong>FADS1 variation modified the effect of nut consumption on circulating FAs. We did not observe clear evidence that it modified the association between nut consumption and type 2 diabetes risk.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"344"},"PeriodicalIF":7.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246459","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":"Circulating short-chain fatty acids and Mediterranean food patterns. A potential role for the prediction of type 2 diabetes risk: The Di@bet.es Study.","authors":"Gemma Llauradó, Lídia Cedó, Elisenda Climent, Joan Badia, Gemma Rojo-Martínez, Juana Flores-Le Roux, Oscar Yanes, Maria Vinaixa, Minerva Granado-Casas, Didac Mauricio, Sonia Fernández-Veledo, Joan Vendrell","doi":"10.1186/s12916-025-04186-9","DOIUrl":"10.1186/s12916-025-04186-9","url":null,"abstract":"<p><strong>Background: </strong>Identifying nutritional patterns associated with developing type 2 diabetes (T2D) can facilitate more effective and personalized dietary interventions. Short-chain fatty acids (SCFAs), key metabolites derived from gut microbiota, are produced through the anaerobic fermentation of dietary fibers. This study aimed to evaluate whether circulating concentrations of SCFAs are associated with specific food consumption patterns and to assess their association with T2D development in at-risk subjects within a prospective cohort (The Di@bet.es Study).</p><p><strong>Methods: </strong>The Di@bet.es study is a prospective, population-based study utilizing random cluster sampling from the Spanish population aged over 18 years (n = 5,072). Among these participants, 4,347 were free of T2D at baseline. Follow-up losses were approximately 45%, resulting in a final re-screened sample of 2,408 subjects. A qualitative food frequency questionnaire evaluated Mediterranean diet (MedDiet) adherence and high-fiber food consumption. The risk of developing T2D was assessed using the FINDRISK. Metabolomics-driven analyses of SCFAs were conducted using gas chromatography-mass spectrometry.</p><p><strong>Results: </strong>Subjects who developed T2D after a median follow-up of seven years had higher baseline circulating concentrations of butyrate and isobutyrate. Circulating concentrations of SCFAs were associated with high-fiber food consumption at baseline. In multivariate analysis, baseline circulating concentrations of butyrate and isobutyrate were independently associated with incident T2D after adjusting for traditional clinical factors. The C-statistics for predicting T2D were 0.847 (95%CI:0.816-0.877) for butyrate and 0.843 (95%CI:0.812-0.875) for isobutyrate in adjusted models, similar to the reference model based on traditional clinical factors (0.840 [95%CI: 0.807-0.873]). Both models improved risk prediction compared to FINDRISK. Dietary patterns did not add predictive value. Sensitivity analysis excluding subjects with prediabetes at baseline confirmed these results. In addition, an association between baseline consumption of high-fiber foods with incident T2D emerged, suggesting a different behaviour between healthy and prediabetic subjects.</p><p><strong>Conclusions: </strong>Baseline circulating concentrations of SCFAs are associated with high-fiber food consumption and independently predict the development of T2D over seven years of follow-up. However, they offer limited improvement in risk prediction compared to traditional risk factors, though they enhance risk prediction as assessed by FINDRISK. Further studies are necessary to evaluate the impact of dietary interventions on SCFA.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"337"},"PeriodicalIF":7.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246455","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 indirect effect of the bivalent human papillomavirus vaccination program: an observational cohort study.","authors":"Marit Middeldorp, Janneke W Duijster, Mirjam J Knol, Birgit H B van Benthem, Johannes Berkhof, Audrey J King, Hester E de Melker","doi":"10.1186/s12916-025-04155-2","DOIUrl":"10.1186/s12916-025-04155-2","url":null,"abstract":"<p><strong>Background: </strong>The impact of human papillomavirus (HPV) vaccination programs depends on the degree of indirect protection against new infections achieved among unvaccinated women. We estimated the indirect effect of bivalent HPV vaccination by comparing the HPV-type incidence in unvaccinated female participants between a cohort offered vaccination in 2009/2010 and a cohort of similar-aged women offered vaccination in 2014.</p><p><strong>Methods: </strong>We compared the incidence rates of HPV types in the HAVANA cohort (follow-up from 2010/2011 until 2015/2016) with those from the HAVANA-2 cohort (2017-2022) using two regression approaches to estimate the indirect effect of HPV vaccination. First, we calculated the incidence ratio (IRR) for a vaccine or cross-protective type in HAVANA-2 versus HAVANA by Poisson regression and compared it to the IRR for a non-cross-protective type. The indirect vaccine effect is defined as 1-ratio of the IRRs. Second, we performed Cox regression with infection by vaccine or cross-protective type as the endpoint and calculated the hazard ratio (HR) for HAVANA-2 versus HAVANA after adjusting for time-varying sociodemographic variables. The indirect effect is defined as 1-HR.</p><p><strong>Results: </strong>We included 661 unvaccinated participants in HAVANA and 927 in HAVANA-2. We observed a significant reduction in incident HPV16 infections of 70.9% (95% CI 48.3-83.7%) with Poisson regression and of 73.1% (95% CI 53.3-84.5%) with Cox regression. For HPV45, significant decreases of 67.3% (95% CI 8.8-88.3%) and 69.8% (95% CI 15.2-89.3%) were observed. For HPV18, HPV31, and HPV33, the indirect effect was not statistically significant.</p><p><strong>Conclusions: </strong>Large indirect effects of the bivalent HPV vaccination program were observed for HPV16 and HPV45 infections.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"335"},"PeriodicalIF":7.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246387","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}