BMC Medicine最新文献

{"title":"Adverse events in the nervous system associated with blinatumomab: a real-world study.","authors":"Wen Gao, Jingwei Yu, Yifei Sun, Zheng Song, Xia Liu, Xue Han, Lanfan Li, Lihua Qiu, Shiyong Zhou, Zhengzi Qian, Xianhuo Wang, Huilai Zhang","doi":"10.1186/s12916-025-03913-6","DOIUrl":"10.1186/s12916-025-03913-6","url":null,"abstract":"<p><strong>Background: </strong>Nervous system toxicity (NST) is a frequent and serious adverse event (AE) associated with blinatumomab, the first bispecific antibody drug targeting CD19 and CD3. Real-world data are needed to better understand the incidence and characteristics of NST in clinical practice.</p><p><strong>Methods: </strong>Data were obtained from the FDA Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence interval progressive neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms were utilized for data mining.</p><p><strong>Results: </strong>A total of 5,962 blinatumomab-related cases were analyzed. NSTs were more frequent in males (44.01%) and younger individuals (18-45 years, 28.39%), with a higher prevalence in the USA (77.99%). Forty-three signals of NST were identified, of which neurotoxicity, neurological symptoms, agnosia, intention tremor, and immune effector cell-associated neurotoxicity syndrome had the highest ROR values. Concomitant use of medication for age, musculoskeletal system, genitourinary system, and sexual hormones were independent risk factors for NST, and age was an independent protective factor for fatal NST. The median time to onset (TTO) for neurological events was 3 days (range, 1 ~ 21). The highest fatality rate for neurological events was observed for increased intracranial pressure disorders, which also had the highest co-occurrence rate with cytokine release syndrome (CRS).</p><p><strong>Conclusions: </strong>Age is an independent protective factor for fatal NST, and CRS leads to a higher fatality rate for NST patients treated with blinatumomab. Thorough medication evaluation should be conducted before administering blinatumomab, especially for high-risk patients with preexisting neurological conditions.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"72"},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363700","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":"Assessing brain-muscle networks during motor imagery to detect covert command-following.","authors":"Emilia Fló, Daniel Fraiman, Jacobo Diego Sitt","doi":"10.1186/s12916-025-03846-0","DOIUrl":"10.1186/s12916-025-03846-0","url":null,"abstract":"<p><strong>Background: </strong>In this study, we evaluated the potential of a network approach to electromyography and electroencephalography recordings to detect covert command-following in healthy participants. The motivation underlying this study was the development of a diagnostic tool that can be applied in common clinical settings to detect awareness in patients that are unable to convey explicit motor or verbal responses, such as patients that suffer from disorders of consciousness (DoC).</p><p><strong>Methods: </strong>We examined the brain and muscle response during movement and imagined movement of simple motor tasks, as well as during resting state. Brain-muscle networks were obtained using non-negative matrix factorization (NMF) of the coherence spectra for all the channel pairs. For the 15/38 participants who showed motor imagery, as indexed by common spatial filters and linear discriminant analysis, we contrasted the configuration of the networks during imagined movement and resting state at the group level, and subject-level classifiers were implemented using as features the weights of the NMF together with trial-wise power modulations and heart response to classify resting state from motor imagery.</p><p><strong>Results: </strong>Kinesthetic motor imagery produced decreases in the mu-beta band compared to resting state, and a small correlation was found between mu-beta power and the kinesthetic imagery scores of the Movement Imagery Questionnaire-Revised Second version. The full-feature classifiers successfully distinguished between motor imagery and resting state for all participants, and brain-muscle functional networks did not contribute to the overall classification. Nevertheless, heart activity and cortical power were crucial to detect when a participant was mentally rehearsing a movement.</p><p><strong>Conclusions: </strong>Our work highlights the importance of combining EEG and peripheral measurements to detect command-following, which could be important for improving the detection of covert responses consistent with volition in unresponsive patients.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"68"},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363704","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":"Prevalence of cardiovascular symptoms in post-acute COVID-19 syndrome: a meta-analysis.","authors":"Li-Wei Huang, Hua-Min Li, Bei He, Xiao-Bo Wang, Qi-Zhi Zhang, Wen-Xing Peng","doi":"10.1186/s12916-025-03908-3","DOIUrl":"10.1186/s12916-025-03908-3","url":null,"abstract":"<p><strong>Background: </strong>Since its emergence in 2019, COVID-19 has continued to pose significant threats to both the physical and mental health of the global population, as well as to healthcare systems worldwide (Raman et al., Eur Heart J 43:1157-1172, 2022). Emerging evidence indicates that COVID-19 may lead to post-acute COVID-19 syndrome (PACS) with cardiovascular implications, potentially driven by factors such as ACE2 interaction with viruses, systemic inflammation, and endothelial dysfunction. However, there remains a limited amount of research on the cardiovascular manifestations of PACS, which may delay the development of optimal treatment strategies for affected patients. Therefore, it is crucial to investigate the prevalence of cardiovascular sequelae in COVID-19 patients and to determine whether COVID-19 infection acts as an independent risk factor for these outcomes.</p><p><strong>Methods: </strong>This meta-analysis adhered to PRISMA guidelines and was registered in PROSPERO (CRD42024524290). A systematic search of PubMed, Embase, and the Cochrane Library was conducted up to March 17, 2024. The primary outcomes included hypertension, palpitations, and chest pain, with pooled effect estimate reported as proportions and odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity and subgroup analysis were performed to assess the robustness of the results and to identify sources of heterogeneity.</p><p><strong>Results: </strong>A total of 37 studies, encompassing 2,965,467 patients, were included in the analysis. Pooled results from case-control studies revealed that, compared to the control group, the ORs of chest pain in the COVID-19 group was 4.0 (95% CI: 1.6, 10.0). The ORs for palpitation and hypertension were 3.4 (95% CI: 1.1, 10.2) and 1.7 (95% CI: 1.6, 1.8), respectively. The proportions of PACS patients experiencing chest pain, palpitation, and hypertension as sequelae were 22% (95% CI: 14%, 33%), 18% (95% CI: 13%, 24%), and 19% (95% CI: 12%, 31%), respectively.</p><p><strong>Conclusions: </strong>Our findings indicate that 15% of COVID-19 patients experience cardiovascular sequelae. Furthermore, COVID-19 infection significantly increases the likelihood of developing these sequelae compared to uninfected individuals. Future research should prioritize investigating the underlying pathological mechanisms and developing targeted preventive and management strategies.</p><p><strong>Trial registration: </strong>CRD42024524290.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"70"},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363710","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":"Global, regional, and national disease burden attributable to high systolic blood pressure in youth and young adults: 2021 Global Burden of Disease Study analysis.","authors":"Chuan He, Saien Lu, Haijie Yu, Yingxian Sun, Xueyao Zhang","doi":"10.1186/s12916-025-03918-1","DOIUrl":"10.1186/s12916-025-03918-1","url":null,"abstract":"<p><strong>Background: </strong>High systolic blood pressure (HSBP) can cause adverse cardiovascular events and is therefore associated with a heavy global disease burden. However, this disease burden is poorly understood in youth and young adults. We aimed to explore this population to better understand the evolving trends in HSBP-related disease burden, which is crucial for effectively controlling and mitigating harmful effects.</p><p><strong>Methods: </strong>This systematic analysis used data from the 2021 Global Burden of Disease Study, spanning 1990-2021. Participants were aged 15-39 years from 204 countries/territories. We analysed HSBP-related disease burden by region, sex, age, and temporal trends. The primary outcomes were disability-adjusted life years (DALYs), mortality rates, and estimated annual percentage change.</p><p><strong>Results: </strong>Globally, the number of HSBP-related deaths among youth and young adults has increased by 36.11% (95% uncertainty interval [95% UI], 20.96-52.37%), whereas the number of DALYs has increased by 37.68% (95% UI, 22.69-53.65%); however, global mortality and DALY rates have remained relatively stable. In 2021, the mortality and DALY rates were 4.29 (95% UI, 3.29-5.28) and 263.37 (95% UI, 201.40-324.46) per 100,000 population, respectively. The overall HSBP-related burden was higher in males than in females, with increasing and decreasing trends for males and females, respectively. Regionally, significant improvements in HSBP-related burden were observed in most high-sociodemographic index (SDI) regions, including high-income Asia Pacific (deaths: percentage change, - 72.65%; DALYs: percentage change, - 69.30%) and Western Europe (deaths: percentage change, - 72.89%; DALYs: percentage change, - 67.48%). In contrast, middle-SDI regions had the highest number of deaths and DALYs in 2021, whereas low-middle-SDI regions had the highest mortality and DALY rates. Furthermore, low-SDI regions experienced the largest increase in the number of deaths and DALYs. The HSBP-related burden increased with age; in addition, the proportion of deaths or DALYs due to ischaemic heart disease and stroke increased with age, reaching > 75% for those > 25 years of age.</p><p><strong>Conclusions: </strong>The increase in global HSBP-related burden among youth and young adults indicates that current preventative efforts are insufficient. Therefore, targeted measures are needed to counter the trends in HSBP-related diseases and reduce disparities across regions and sexes.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"74"},"PeriodicalIF":7.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363706","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 DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID.","authors":"Andrea Polli, Lode Godderis, Dries S Martens, Madhura Shekhar Patil, Jolien Hendrix, Arne Wyns, Jente Van Campenhout, Emma Richter, Lara Fanning, Olivia Vandekerckhove, Eveline Claeys, Wim Janssens, Natalie Lorent","doi":"10.1186/s12916-025-03881-x","DOIUrl":"10.1186/s12916-025-03881-x","url":null,"abstract":"<p><strong>Background: </strong>Long-COVID is defined as the persistency or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. Common persistent symptoms are fatigue, sleep disturbances, post-exertional malaise (PEM), pain, and cognitive problems. Long-COVID is estimated to be present in about 65 million people. We aimed to explore clinical and biological factors that might contribute to Long-COVID.</p><p><strong>Methods: </strong>Prospective longitudinal cohort study including patients infected with SARS-CoV-2 between March 2020 and March 2022. Patients were assessed between 4 and 12 months after infection at the COVID follow-up clinic at UZ Leuven. We performed a comprehensive clinical assessment (including questionnaires and the 6-min walking test) and biological measures (global DNA methylation, telomere length, mitochondrial DNA copy number, inflammatory cytokines, and serological markers such as C-reactive protein, D-dimer, troponin T).</p><p><strong>Results: </strong>Of the 358 participants, 328 were hospitalised, of which 130 had severe symptoms requiring intensive care admission; 30 patients were ambulatory referrals. Based on their clinical presentation, we could identify 6 main clusters. One-hundred and twenty-seven patients (35.4%) belonged to at least one cluster. The bigger cluster included PEM, fatigue, sleep disturbances, and pain (n = 57). Troponin T and telomere shortening were the two main markers predicting Long-COVID and PEM-fatigue symptoms.</p><p><strong>Conclusions: </strong>Long-COVID is not just one entity. Different clinical presentations can be identified. Cardiac involvement (as measured by troponin T levels) and telomere shortening might be a relevant risk factor for developing PEM-fatigue symptoms and deserve further exploring.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"60"},"PeriodicalIF":7.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122150","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":"Implementation of a rapid host-protein diagnostic test for distinguishing bacterial and viral infections in adults presenting to urgent care centers: a pragmatic cohort study.","authors":"Boaz Kalmovich, Daniella Rahamim-Cohen, Ilan Yehoshua, Sara Kivity, Noam Orvieto, Shirley Shapiro Ben David","doi":"10.1186/s12916-025-03903-8","DOIUrl":"10.1186/s12916-025-03903-8","url":null,"abstract":"<p><strong>Background: </strong>Urgent care centers (UCCs) are a growing segment of healthcare with high rates of inappropriate antibiotic use. MeMed BV® (MMBV) is a blood test that differentiates bacterial from viral infections. Between April 2022 and March 2023, we introduced MMBV into routine care at ten UCCs. The primary objective was to assess MMBV's impact on antibiotic use; the secondary objective was to assess whether MMBV aided in patient management.</p><p><strong>Methods: </strong>A pragmatic prospective cohort study. Physicians who ordered MMBV reported electronically (in real-time) whether they intended to prescribe antibiotics before ordering the test and upon UCC discharge whether MMBV aided in patient management. Hospitalizations were recorded for 7 days post-UCC discharge.</p><p><strong>Results: </strong>During implementation, 3920 MMBV tests were ordered for adults (age ≥ 18) by 144 physicians. The study cohort had 59% female patients and the median age was 42 years (IQR 31-58). For the primary objective, 3262 cases were included. MMBV indicated 629/3262 (19.3%) cases of potentially unwarranted antibiotics, of which physicians avoided prescriptions in 397/629 (63.1%). MMBV indicated 405/3262 (12.4%) cases of potentially missed bacterial infections. Physicians prescribed antibiotics to 283/405 (69.9%). MMBV adherence was associated with fewer hospitalizations (7.8% vs. 30.3%, p < 0.001). For the secondary objective, 2901 cases were included. Physicians reported MMBV aided patient management in 2494/2901 (86.0%) cases and contributed to avoiding emergency department referrals in 595/2901 (20.5%).</p><p><strong>Conclusions: </strong>Implementing MMBV aided urgent care center physicians in their clinical decision-making and may have contributed to appropriate antibiotic use, better resource utilization, and patient management.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"63"},"PeriodicalIF":7.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122168","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":"Single-nucleotide polymorphisms in dizygotic twin ovine fetuses are associated with discordant responses to antenatal steroid therapy.","authors":"Erin L Fee, Haruo Usuda, Sean W D Carter, Hideyuki Ikeda, Tsukasa Takahashi, Yuki Takahashi, Yusaku Kumagai, Michael W Clarke, Demelza J Ireland, John P Newnham, Masatoshi Saito, Sebastian E Illanes, Binny Priya Sesurajan, Liang Shen, Mahesh A Choolani, Gokce Oguz, Adaikalavan Ramasamy, Sara Ritchie, Andrew Ritchie, Alan H Jobe, Matthew W Kemp","doi":"10.1186/s12916-025-03910-9","DOIUrl":"10.1186/s12916-025-03910-9","url":null,"abstract":"<p><strong>Background: </strong>Antenatal steroid (ANS) therapy is given to women at risk of preterm delivery to accelerate fetal lung maturation. However, the benefit of ANS therapy is variable and how maternal and fetal factors contribute to this observed variability is unknown. We aimed to test the degree of concordance in preterm lung function, and correlate this with genomic, transcriptomic, and pharmacokinetic variables in preterm dizygotic twin ovine fetuses.</p><p><strong>Methods: </strong>Thirty-one date-mated ewes carrying twin fetuses at 123 ± 1 days' gestation received maternal intramuscular injections of either (i) 1 × 0.25 mg/kg betamethasone phosphate and acetate (CS1, n = 11 twin pairs) or (ii) 2 × 0.25 mg/kg betamethasone phosphate and acetate, 24 h apart (CS2, n = 10 twin pairs) or (iii) 2 × saline, 24 h apart (negative control, n = 10 twin pairs). Fetuses were surgically delivered 24 h after their final treatment and ventilated for 30 min.</p><p><strong>Results: </strong>ANS-exposed female fetuses had lower arterial partial pressure of carbon dioxide (PaCO₂) values than male fetuses (76.5 ± 38.0 vs. 97.2 ± 42.5 mmHg), although the observed difference was not statistically significant (p = 0.1). Only 52% of ANS-treated twins were concordant for lung maturation responses. There was no difference in fetal lung tissue or plasma steroid concentrations within or between twin pairs. Genomic analysis identified 13 single-nucleotide polymorphisms (SNPs) statistically associated with ANS-responsiveness, including in the proto-oncogene MET and the transcription activator STAT1.</p><p><strong>Conclusions: </strong>Twin fetal responses and ANS tissue levels were comparable with those from singleton fetuses in earlier studies. Twin ovine fetuses thus benefit from ANS in a similar manner to singleton fetuses, and a larger dose of betamethasone is not required. Assuming no difference in input from the placental or maternal compartments, fetal lung responses to ANS therapy in dizygotic twin preterm lambs are dependent on the fetus itself. These data suggest a potential heritable role in determining ANS responsiveness.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"65"},"PeriodicalIF":7.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122178","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":"Association of accelerated phenotypic aging, genetic risk, and lifestyle with progression of type 2 diabetes: a prospective study using multi-state model.","authors":"Lulu Pan, Yahang Liu, Chen Huang, Yifang Huang, Ruilang Lin, Kecheng Wei, Ye Yao, Guoyou Qin, Yongfu Yu","doi":"10.1186/s12916-024-03832-y","DOIUrl":"10.1186/s12916-024-03832-y","url":null,"abstract":"<p><strong>Background: </strong>Aging is a major risk factor for type 2 diabetes (T2D), but individuals of the same chronological age may vary in their biological aging rate. The associations of Phenotypic Age Acceleration (PhenoAgeAccel), a new accelerated biological aging indicator based on clinical chemistry biomarkers, with the risk of dynamic progression remain unclear. We aimed to assess these associations and examine whether these associations varied by genetic risk and lifestyle.</p><p><strong>Methods: </strong>We conducted a prospective cohort study that included 376,083 adults free of T2D and diabetes-related events at baseline in UK Biobank. PhenoAgeAccel > 0 and ≤ 0 were defined as biologically older and younger than chronological age. The outcomes of interest were incident T2D, diabetic complications, and mortality. Hazard ratios (HRs) with 95% confidence intervals (CIs) and population attributable fractions (PAFs) for these associations were calculated using multi-state model.</p><p><strong>Results: </strong>During a median follow-up of 13.7 years, 17,615 participants developed T2D, of whom, 4,524 subsequently developed complications, and 28,373 died. Being biologically older was associated with increased risks of transitions from baseline to T2D (HR 1.77, 95% CI 1.71-1.82; PAF 24.8 [95% CI 23.5-26.2]), from T2D to diabetic complications (1.10, 1.04-1.17; 4.4 [1.4-7.4]), from baseline to all-cause death (1.53, 1.49-1.57; 17.6 [16.6-18.6]), from T2D to all-cause death (1.14, 1.03-1.26; 7.4 [1.8-13.0]), and from diabetic complications to all-cause death (1.32, 1.15-1.51; 15.4 [7.5-23.2]) than being biologically younger. Additionally, participants with older biological age and high genetic risk had a higher risk of incident T2D (4.76,4.43-5.12;18.2 [17.5-19.0]) than those with younger biological age and low genetic risk. Compared with participants with younger biological age and healthy lifestyle, those with older biological age and unhealthy lifestyle had higher risks of transitions in the T2D trajectory, with HRs and PAFs ranging from 1.34 (1.16-1.55; 3.7 [1.8-5.6]) to 5.39 (5.01-5.79; 13.0 [12.4-13.6]).</p><p><strong>Conclusions: </strong>PhenoAgeAccel was consistently associated with an increased risk of all transitions in T2D progression. It has the potential to be combined with genetic risk to identify early T2D incidence risk and may guide interventions throughout T2D progression while tracking their effectiveness.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"62"},"PeriodicalIF":7.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122145","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":"Immune microenvironment spatial landscapes of tertiary lymphoid structures in gastric cancer.","authors":"Yi Xie, Haoxin Peng, Yajie Hu, Keren Jia, Jiajia Yuan, Dan Liu, Yanyan Li, Xujiao Feng, Jian Li, Xiaotian Zhang, Yu Sun, Lin Shen, Yang Chen","doi":"10.1186/s12916-025-03889-3","DOIUrl":"10.1186/s12916-025-03889-3","url":null,"abstract":"<p><strong>Background: </strong>Tertiary lymphoid structures (TLS) correlate with tumour prognosis and immunotherapy responses in gastric cancer (GC) studies. However, understanding the complex and diverse immune microenvironment within TLS requires comprehensive analysis.</p><p><strong>Methods: </strong>We examined the prognostic impact of TLS within the tumour core (TC) of 59 GC patients undergoing immunotherapy. Multispectral fluorescence imaging was employed to evaluate variations in immune cell infiltration across different TLS sites among 110 GC patients, by quantifying immune cell density and spatial characteristics. We also generated a single-cell transcriptomic atlas of TLS-positive (n = 4) and TLS-negative (n = 8) microenvironments and performed spatial transcriptomics (ST) analysis on two samples.</p><p><strong>Results: </strong>TLS presence in the TC significantly correlated with improved immune-related overall survival (P = 0.049). CD8⁺LAG-3^-PD-1⁺TIM-3^-, CD4⁺PD-L1⁺, and CD4⁺FoxP3^- T cell densities were significantly higher in the TLS within TC compared to tumour and stromal regions. Immune cells within TLS exhibited closer intercellular proximity than those outside TLS. Five key density and spatial characteristics of immune cells within TLS in the TC were selected to develop the Density and Spatial Score risk model. Single-cell RNA sequencing revealed strong intercellular interactions in the presence of TLS within the microenvironment. However, TLS-absent environment facilitated tumour cell interactions with immune cells through MIF- and galectin-dependent pathways, recruiting immunosuppressive cells. ST analysis confirmed that T and B cells co-localise within TLS, enhancing immune response activation compared to cancer nests and exerting a strong anti-tumour effect.</p><p><strong>Conclusions: </strong>TLS presence facilitates frequent cell-to-cell communication, forming an active immune microenvironment, highlighting the prognostic value of TLS.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"59"},"PeriodicalIF":7.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122155","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":"Visceral adipose tissue area and proportion provide distinct reflections of cardiometabolic outcomes in weight loss; pooled analysis of MRI-assessed CENTRAL and DIRECT PLUS dietary randomized controlled trials.","authors":"Hadar Klein, Hila Zelicha, Anat Yaskolka Meir, Ehud Rinott, Gal Tsaban, Alon Kaplan, Yoash Chassidim, Yftach Gepner, Matthias Blüher, Uta Ceglarek, Berend Isermann, Michael Stumvoll, Ilan Shelef, Lu Qi, Jun Li, Frank B Hu, Meir J Stampfer, Iris Shai","doi":"10.1186/s12916-025-03891-9","DOIUrl":"10.1186/s12916-025-03891-9","url":null,"abstract":"<p><strong>Background: </strong>Visceral adipose tissue (VAT) is well established as a pathogenic fat depot, whereas superficial subcutaneous adipose tissue (SAT) is associated with either an improved or neutral cardiovascular state. However, it is unclear to what extent VAT area (VATcm²) and its proportion of total abdominal adipose tissue (VAT%) are distinguished in predicting cardiometabolic status and clinical outcomes during weight loss.</p><p><strong>Methods: </strong>We integrated magnetic resonance imaging (MRI) measurements of VAT, deep-SAT, and superficial-SAT from two 18-month lifestyle weight loss clinical trials, CENTRAL and DIRECT PLUS (n = 572).</p><p><strong>Results: </strong>At baseline, the mean VATcm² was 144.8cm² and VAT% = 28.2%; over 18 months, participants lost 28cm² VATcm² (- 22.5%), and 1.3 VAT% units. Baseline VATcm² and VAT% were similarly associated with metabolic syndrome, hypertension, and diabetes status, while VAT% better classified hypertriglyceridemia. Conversely, higher VATcm² was associated with elevated high-sensitivity C-reactive protein (hsCRP), while VAT% was not. After 18 months of lifestyle intervention, both VATcm² and VAT% loss were significantly associated with decreased triglycerides, HbA1c, ferritin, and liver enzymes, and increased HDL-c levels beyond weight loss (FDR < 0.05). Only VATcm² loss was correlated with decreased HOMA-IR, chemerin, and leptin levels.</p><p><strong>Conclusions: </strong>MRI follow-up of 572 participants over 18 months of weight loss intervention suggests that although increased VATcm² and VAT% exhibit similar clinical manifestations, it might be preferable to examine VAT% when exploring lipid status, while VATcm² may better reflect inflammatory and glycemic states.</p><p><strong>Trial registration: </strong>CENTRAL (Clinical-trials-identifier: NCT01530724); DIRECT PLUS (Clinical-trials-identifier: NCT03020186).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"57"},"PeriodicalIF":7.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122180","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}