BMC Medicine最新文献

{"title":"Correction: The use and impact of surveillance-based technology initiatives in inpatient and acute mental health settings: a systematic review.","authors":"Jessica L Griffiths, Katherine R K Saunders, Una Foye, Anna Greenburgh, Ciara Regan, Ruth E Cooper, Rose Powell, Ellen Thomas, Geoff Brennan, Antonio Rojas-García, Brynmor Lloyd-Evans, Sonia Johnson, Alan Simpson","doi":"10.1186/s12916-025-03979-2","DOIUrl":"10.1186/s12916-025-03979-2","url":null,"abstract":"","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"141"},"PeriodicalIF":7.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584778","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":"Correction: Metabolomics- and proteomics-based multi-omics integration reveals early metabolite alterations in sepsis-associated acute kidney injury.","authors":"Pengfei Huang, Yanqi Liu, Yue Li, Yu Xin, Chuanchuan Nan, Yinghao Luo, Yating Feng, Nana Jin, Yahui Peng, Dawei Wang, Yang Zhou, Feiyu Luan, Xinran Wang, Xibo Wang, Hongxu Li, Yuxin Zhou, Weiting Zhang, Yuhan Liu, Mengyao Yuan, Yuxin Zhang, Yuchen Song, Yu Xiao, Lifeng Shen, Kaijiang Yu, Mingyan Zhao, Lixin Cheng, Changsong Wang","doi":"10.1186/s12916-025-03980-9","DOIUrl":"10.1186/s12916-025-03980-9","url":null,"abstract":"","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"143"},"PeriodicalIF":7.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584776","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":"Psychiatric and neuropsychiatric sequelae of COVID-19 within 2 years: a multinational cohort study.","authors":"Yi Chai, Ivan C H Lam, Kenneth K C Man, Joseph F Hayes, Eric Y F Wan, Xue Li, Celine S L Chui, Wallis C Y Lau, Xiaoyu Lin, Can Yin, Min Fan, Esther W Chan, Ian C K Wong, Hao Luo","doi":"10.1186/s12916-025-03952-z","DOIUrl":"10.1186/s12916-025-03952-z","url":null,"abstract":"<p><strong>Background: </strong>The long-term psychiatric and neuropsychiatric sequelae of COVID-19 across diverse populations remain not fully understood. This cohort study aims to investigate the short-, medium-, and long-term risks of psychiatric and neuropsychiatric disorders following COVID-19 infection in five countries.</p><p><strong>Methods: </strong>This population-based multinational network study used electronic medical records from France, Italy, Germany, and the UK and claims data from the USA. The initial target and comparator cohorts were identified using an exact matching approach based on age and sex. Individuals diagnosed with COVID-19 or those with a positive SARS-CoV-2 screening test between December 1, 2019, and December 1, 2020, were included as targets. Up to ten comparators without COVID-19 for each target were selected using the propensity score matching approach. All individuals were followed from the index date until the end of continuous enrolment or the last healthcare encounter. Cox proportional hazard regression models were fitted to estimate the risk of incident diagnosis of depression, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, psychoses, personality disorders, self-harm and suicide, sleep disorders, dementia, and neurodevelopmental disorders within the first 6 months (short-term), 6 months to 1 year (medium-term), and 1 to 2 years (long-term) post-infection.</p><p><strong>Results: </strong>A total of 303,251 individuals with COVID-19 and 22,108,925 individuals without COVID-19 from five countries were originally included. Within the first 6 months, individuals with COVID-19 had a significantly higher risk of any studied disorders in all databases, with Hazard Ratios (HRs) ranging from 1.14 (95% CI, 1.07-1.22) in Germany to 1.89 (1.64-2.17) in Italy. Increased risks were consistently observed for depression, anxiety disorders, and sleep disorders across almost all countries. During the medium- and long-term periods, higher risks were observed only for depression (medium-term: 1.29, 1.18-1.41; long-term: 1.36, 1.25-1.47), anxiety disorders (medium-term: 1.29, 1.20-1.38; long-term: 1.37, 1.29-1.47), and sleep disorders (medium-term: 1.10, 1.01-1.21; long-term: 1.14, 1.05-1.24) in France, and dementia (medium-term: 1.65, 1.28-2.10) in the UK.</p><p><strong>Conclusions: </strong>Our study suggests that increased risks of psychiatric and neuropsychiatric outcomes were consistently observed only within, and not after, the 6-month observation period across all databases, except for certain conditions in specific countries.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"144"},"PeriodicalIF":7.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584790","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":"Effect of a single-dose denosumab on mineral homeostasis in infertile men: insights from a pilot intervention study and a randomized controlled trial.","authors":"Sam Kafai Yahyavi, Rune Holt, Li Juel Mortensen, Ida Marie Boisen, Lív Bech Árting, Anne Jørgensen, Anders Juul, Martin Blomberg Jensen","doi":"10.1186/s12916-025-03958-7","DOIUrl":"10.1186/s12916-025-03958-7","url":null,"abstract":"<p><strong>Background: </strong>Denosumab, a drug that inhibits RANKL to reduce bone resorption in osteoporotic postmenopausal women, has been shown to improve semen quality in a subgroup of infertile men. This study aimed to investigate the effects of denosumab on mineral homeostasis in young infertile men.</p><p><strong>Methods: </strong>Secondary data from two clinical trials designed to test the effect on semen quality were used: (1) a pilot intervention study with 12 men receiving a single-dose of 60 mg denosumab and (2) a single-center, double-blinded, randomized clinical trial, where 100 infertile men were randomized 1:1 to receive denosumab 60 mg once sc. or placebo. A linear mixed model for repeated measures was employed to analyze data from follow-up samples.</p><p><strong>Results: </strong>In the pilot intervention study, denosumab treatment induced a decrease in ionized calcium 5, 20, 40, and 80 days after treatment compared with baseline (all p < 0.05). Serum phosphate decreased on all time points up to and including day 40 (all p < 0.05), while alkaline phosphatase was only lowered at 40 days and onwards (p = 0.014). Serum PTH increased significantly at all time points up to and including day 80 (p = 0.026). One hundred eighty days after treatment, all reported analyses were comparable to baseline levels. The observed temporal changes were confirmed in the RCT with differences in serum calcium (p < 0.001) and phosphate (p < 0.001) on day 14, PTH (p < 0.002), and alkaline phosphatase (p < 0.001) on days 80 and 160. Denosumab treatment had no significant effect on vitamin D status, renal function, or serum albumin concentration after 80 and 160 days.</p><p><strong>Conclusions: </strong>Small but significant changes in mineral homeostasis and bone mineral content were observed but the changes were transient and normalized after treatment cessation. A single injection of denosumab in infertile men appears to have no major long-term impact on bone or mineral homeostasis.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03030196. Registered January 24, 2017.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"145"},"PeriodicalIF":7.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584782","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":"A decision-analytical perspective on incorporating multiple outcomes in the production of clinical prediction models: defining a taxonomy of risk estimands.","authors":"Glen P Martin, Alexander Pate, Siân Bladon, Matthew Sperrin, Richard D Riley","doi":"10.1186/s12916-025-03978-3","DOIUrl":"10.1186/s12916-025-03978-3","url":null,"abstract":"<p><strong>Background: </strong>Clinical prediction models (CPMs) estimate an individual's risk of current or future outcome events, using information available about the individual at the time of prediction. While most CPMs are developed to predict a single outcome event, many clinical decisions require considering the risks of multiple outcome events. For example, decision-making for anticoagulation therapy involves assessing an individual's risks of both blood clot and bleeding, while decision-making around interventions for multimorbidity prevention requires an understanding of the risks of developing multiple long-term conditions. However, determining when and how to incorporate multiple outcomes into CPMs remains challenging. This article aims to raise awareness of multiple outcome prediction and present clinical examples where such prediction is essential to help inform individual decision-making.</p><p><strong>Main text: </strong>A range of analytical methods are available to develop multiple-outcome CPMs, but there are frequent malapropisms and heterogeneity in terminology across this literature, making it difficult to identify/compare possible methods. Selecting the appropriate method should depend on the intended risk estimand-the type of predicted risks that we wish the CPM to estimate-but this is often not defined or reported. Using clinical examples and a decision-analytical perspective, we present a taxonomy of risk estimands to frame different clinical contexts requiring multiple-outcome CPMs. We outline four levels of risk estimands: (i) single-outcome risk, (ii) competing-outcome risk, (iii) composite-outcome risk, and (iv) risk of multiple outcome combinations. We demonstrate how a decision-analytical and utility-theory lens can help define the risk estimand for a given clinical scenario, based on the model's intended use.</p><p><strong>Conclusions: </strong>Clearly defining and reporting the risk estimand is essential for all prediction model studies. A decision-analytical framework aids in selecting the most appropriate estimand for a given prediction task and in determining when and how to incorporate multiple outcomes into CPM development.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"142"},"PeriodicalIF":7.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572031","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":"Value of cannabidiol as adjunctive treatment for Lennox Gastaut syndrome: cost-effectiveness and budget impact analysis.","authors":"Zahra Goudarzi, Farhad Lotfi, Rahil Sadat Shahtaheri, Nasrin Moradi, Mohsen Taghizadeh, Khosro Keshavarz","doi":"10.1186/s12916-025-03972-9","DOIUrl":"10.1186/s12916-025-03972-9","url":null,"abstract":"<p><strong>Background: </strong>Lennox-Gastaut syndrome (LGS) is a severe encephalopathic disease that leads to a decrease in the quality of life, physical injury, psychosocial impairment, and a significant increase in treatment costs. Cannabidiol (CBD) is approved for the adjunctive treatment of tonic-colonic seizures in LGS. This study aimed to determine the cost-effectiveness of CBD compared to the usual treatment in patients with LGS syndrome.</p><p><strong>Methods: </strong>We developed a lifetime-horizon Markov model to compare the cost-effectiveness of adjunctive CBD versus usual care. Additionally, we performed a budget impact analysis over a 5-year time horizon. The findings were presented as the incremental cost-effectiveness ratio (ICER) for CEA, with a willingness to pay threshold of $18,261 per QALY gained, and as the difference in the overall budget ($) between the scenarios with and without CBD for budget impact assessment.</p><p><strong>Results: </strong>In the base case scenario, CBD was cost-effective compared with usual care $6573 per QALY. Sensitivity analyses substantiated these results. From a healthcare perspective, there is a 77% probability that CBD is cost-effective at a willingness to pay of $18,261 per quality-adjusted life-year (QALY). Overall, the market access of CBD was associated to an increased budget of about $3,459,846 (+ 33%) in the next 5 years simulated.</p><p><strong>Conclusions: </strong>Compared to usual care, CBD seems to be cost-effective in LGS patients and sustainable, with less than 34% overall budget increased in the next 5 years. Future studies need to confirm our results in the real word setting and in other countries.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"135"},"PeriodicalIF":7.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555893","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":"Lifestyle behaviours do not moderate the association between childhood maltreatment and comorbid depression and cardiometabolic disease in older adults: a meta-analysis.","authors":"Olujolagbe Layinka, Camille Souama, Serena Defina, Vilte Baltramonaityte, Charlotte A M Cecil, Punit Shah, Yuri Milaneschi, Femke Lamers, Brenda W J H Penninx, Esther Walton","doi":"10.1186/s12916-025-03950-1","DOIUrl":"10.1186/s12916-025-03950-1","url":null,"abstract":"<p><strong>Background: </strong>Comorbidity between depression and cardiometabolic diseases is an emerging health concern, with childhood maltreatment as a major risk factor. These conditions are also linked to unhealthy lifestyle behaviours such as physical inactivity, smoking, and alcohol intake. However, the precise degree to which lifestyle behaviours moderate the risk between childhood maltreatment and comorbid depression and cardiometabolic disease is entirely unknown.</p><p><strong>Methods: </strong>We analysed clinical and self-reported data from four longitudinal studies (N_pooled = 181,423; mean follow-up period of 5-18 years) to investigate the moderating effects of physical activity, smoking, and alcohol intake, on the association between retrospectively reported childhood maltreatment and i) depression, ii) cardiometabolic disease and iii) their comorbidity in older adults (mean age range of 47-66 years). Estimates of these moderation effects were derived using multinomial logistic regressions and then meta-analysed.</p><p><strong>Results: </strong>No meaningful moderation effects were detected for any of the lifestyle behaviours on the association between childhood maltreatment and each health outcome. Physical activity was linked to lower odds of depression (OR [95% CI] = 0.94 [0.92; 0.96]), while smoking was a risk factor for all three outcomes (OR [95% CI] = 1.16 [1.04; 1.31] or larger). Alcohol intake was associated with slightly lower odds of comorbidity (OR [95% CI] = 0.69 [0.66; 0.73]), although this association was not stable across all sensitivity analyses.</p><p><strong>Conclusions: </strong>Lifestyle behaviours did not moderate the risk association between childhood maltreatment and depression, cardiometabolic disease, and their comorbidity in older adults. However, we confirmed that childhood maltreatment was associated with these conditions. Further research should address the limitations of this study to elucidate the most optimal targets for intervention.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"133"},"PeriodicalIF":7.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555872","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":"Longitudinal multi-omics analysis of convalescent individuals with respiratory sequelae 6-36 months after COVID-19.","authors":"Huqin Yang, Lujia Guan, Yi Xue, Xuyan Li, Leyi Gao, Zhijin Zhang, Haifan Zhang, Haomiao Ma, Fengjiao Liu, Xuan Huang, Zhaohui Tong, Jieqiong Li","doi":"10.1186/s12916-025-03971-w","DOIUrl":"10.1186/s12916-025-03971-w","url":null,"abstract":"<p><strong>Background: </strong>Approximately 10-30% of individuals continue to experience symptoms classified as post-acute sequelae of coronavirus disease 2019 (COVID-19 (PASC)). PASC is a multisystem condition primarily characterized by respiratory symptoms, such as reduced diffusing capacity for carbon monoxide (DLco). Although many studies have investigated the pathogenesis of acute COVID-19, the long-term molecular changes in COVID-19 convalescents with PASC remain poorly understood.</p><p><strong>Methods: </strong>We prospectively recruited 70 individuals who had been diagnosed with COVID-19 from 7 January 2020 to 29 May 2020 (i.e., COVID-19 convalescents); we performed follow-up visits at 6 months, 1 year, 2 years, and 3 years after hospital discharge. Thirty-five healthy controls (CONs), recruited from a physical examination center before the COVID-19 pandemic, served as a comparison group. We explored the proteomic and metabolomic profiles of 174 plasma samples from the 70 COVID-19 convalescents and 35 CONs.</p><p><strong>Results: </strong>We performed a comprehensive molecular analysis of COVID-19 convalescents to investigate host changes up to 3 years after hospital discharge. Our multi-omics analysis revealed activation of cytoskeletal organization and glycolysis/gluconeogenesis, as well as suppression of gas transport and adaptive immune responses, in COVID-19 convalescents. Additionally, metabolites involved in glutathione metabolism; alanine, aspartate, and glutamate metabolism; and ascorbate and aldarate metabolism were significantly upregulated in COVID-19 convalescents. Pulmonary and molecular abnormalities persisted for 3 years in COVID-19 convalescents; impaired diffusing capacity for carbon monoxide (DLco) was the most prominent feature. We used this multi-omics profile to develop a model involving one protein (heterogeneous nuclear ribonucleoprotein K (HNRNPK)) and two metabolites (arachidonoyl-EA and 1-O-(2r-hydroxy-pentadecyl)-sn-glycerol)) for identification of COVID-19 convalescents with abnormal DLco.</p><p><strong>Conclusions: </strong>These data provide insights concerning molecular sequelae among COVID-19 convalescents up to 3 years after hospital discharge, clarify mechanisms driving respiratory sequelae, and support the development of a novel model to predict reduced DLco. This longitudinal multi-omics analysis may illuminate the trajectory of altered lung function in COVID-19 convalescents.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"134"},"PeriodicalIF":7.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555887","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":"Elevated CD10^- neutrophils correlate with non-response and poor prognosis of CD19 CAR T-cell therapy for B-cell acute lymphoblastic leukemia.","authors":"Jinli Zhu, Ji Zhou, Xue Liang, Furun An, Yangyang Ding, Xunyi Jiao, Meng Xiao, Fan Wu, Yingwei Li, Hao Xiao, Ying Pan, Huiping Wang, Zhimin Zhai","doi":"10.1186/s12916-025-03968-5","DOIUrl":"10.1186/s12916-025-03968-5","url":null,"abstract":"<p><strong>Background: </strong>The primary challenges in CD19-specific chimeric antigen receptor T-cell (CD19 CAR T) therapy for patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL) are non-response and relapse; it is urgent to reveal these mechanisms. Neutrophils play a critical role in the immunosuppressive tumor microenvironment (TME), which can hinder CAR T efficacy. Our previous research identified a subset of immunosuppressive neutrophils with a special phenotype (CD14^-CD10^-CD45^-HLA-DR^-SSC⁺⁺, termed CD10^- neuts), which suppress T cell function. Therefore, we speculate that CD10^- neuts may also influence CAR T efficacy, and this study aims to clinically validate this hypothesis.</p><p><strong>Methods: </strong>We enrolled 44 patients with r/r B-ALL undergoing CD19 CAR T therapy and 47 healthy controls (HCs). Peripheral blood samples were obtained prior to CAR T infusion to detect CD10^- neuts levels by flow cytometry. Key parameters included the percentage of CD10^- neuts in neutrophils (CD10^- neuts/neutrophils), in all nucleated cells (CD10^- neuts/nucleated cells), and the absolute count of CD10^- neuts. We analyzed the correlations between these indicators and therapeutic response, relapse-free survival (RFS), overall survival (OS), and CAR T cell persistence time.</p><p><strong>Results: </strong>CD10^- neuts levels were significantly elevated in patients with r/r B-ALL compared to HCs. Additionally, non-responding patients exhibited higher CD10^- neuts levels than those in remission. Specifically, CD10^- neuts/neutrophils, CD10^- neuts/nucleated cells, and absolute CD10^- neuts count were 64.44% vs. 25.43% (p = 0.004), 28.61% vs. 9.81% (p = 0.018), and 766.1/μL vs. 152.9/μL (p = 0.04), respectively. Among these indices, only CD10^- neuts/neutrophils emerged as an independent risk factor for CAR T response (OR = 19.8, p = 0.013), relapse (HR = 4.704, p = 0.004), and survival (HR = 6.417, p = 0.001). Patients with CD10^- neuts/neutrophils ≥ 21.57% demonstrated significantly shorter RFS and OS compared to those with lower levels (p = 0.001; p = 0.0002). Furthermore, CD10^- neuts/neutrophils were negatively correlated with the persistence time of CAR T cells.</p><p><strong>Conclusions: </strong>As one of the key factors in the TME, abnormally elevated CD10^- neuts correlate with CAR T therapy resistance. Targeting these neutrophils could enhance the effectiveness of CAR T treatment.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"138"},"PeriodicalIF":7.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555773","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":"Agomelatine as adjunctive therapy with SSRIs or SNRIs for major depressive disorder: a multicentre, double-blind, randomized, placebo-controlled trial.","authors":"Yumeng Ju, Wenwen Ou, Haoran Chen, Limin Yang, Yan Long, Hui Liang, Zhenman Xi, Mei Huang, Wentao Chen, Guanyi Lv, Fangzhou Shao, Bangshan Liu, Jin Liu, Zexuan Li, Mei Liao, Weiye Liang, Zhijian Yao, Yan Zhang, Lingjiang Li","doi":"10.1186/s12916-025-03951-0","DOIUrl":"10.1186/s12916-025-03951-0","url":null,"abstract":"<p><strong>Background: </strong>In general, traditional antidepressants often have limited efficacy in patients with major depressive disorder (MDD). Agomelatine, as an antidepressant with a different mechanism of action, might have adjunctive effects on traditional antidepressants. This study aimed to investigate the augmentation effect of agomelatine versus placebo in treating MDD patients who failed to respond to selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs).</p><p><strong>Methods: </strong>This is an 8-week, multi-centred, double-blinded, randomized, and placebo-controlled trial. Participants diagnosed with MDD and demonstrated inadequate response to SSRI or SNRI lasting at least 2 weeks were randomly allocated to receive either agomelatine or placebo in conjunction with SSRIs or SNRIs. The 17 items of the Hamilton Depression Scale (HAMD-17) were employed to assess depression severity. The primary outcome is the total score of HAMD-17 at week 8. Secondary outcomes included HAMD-17 scores at weeks 2 and 4 and clinical remission and response over 8 weeks. Adverse events (AEs) reported in both groups were recorded. A linear mixed model was established for both primary and secondary outcomes.</p><p><strong>Results: </strong>A total of 123 eligible participants were included, among which 60 were randomized into the agomelatine group, and 63 were randomized into the placebo group. The between-group difference in HAMD-17 score reduction from baseline to week 8 was not significant (difference = - 0.12, 95% CI = - 3.94 to 3.70, P = 0.90; Cohen's d = 0.022). In addition, we did not observe significant differences between the two treatment groups for secondary outcomes, including response remission, and AEs.</p><p><strong>Conclusions: </strong>This study did not obtain significant findings in favour of the augmentation effect of agomelation for MDD patients. However, agomelatine was generally well tolerated and demonstrated a favourable safety profile when used in combination with SSRIs and SNRIs.</p><p><strong>Trial registration: </strong>This trial is registered at ClinicalTrials.gov ( https://clinicaltrials.gov ), the registration number is NCT04589143.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"137"},"PeriodicalIF":7.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555850","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}