EClinicalMedicine最新文献

{"title":"Safety and immunogenicity of UB-612 heterologous booster in adults primed with mRNA, adenovirus, or inactivated COVID-19 vaccines: a randomized, active-controlled, Phase 3 trial.","authors":"Alexander Rumyantsev, Lixia Wang, Shixia Wang, Tracy Kemp, Alana Wriggins, Amy Burks, Danielle Fisher, Katie Brokke, Amy Fix, Susan Hensley, Maggie Lewis, Ray Zhu, Kate Wang, Carolyn Shasha, Giulia Piccini, Alessandro Manenti, Emanuele Montomoli, Rodrigo DeAntonio, Xavier Saez-Llorens, Milagros Chan, Edison Alberto, Ma Dovie Lallaine Borra, Anjuli May Jaen, Gray Heppner, Ulo Palm, Thomas P Monath","doi":"10.1016/j.eclinm.2025.103349","DOIUrl":"10.1016/j.eclinm.2025.103349","url":null,"abstract":"<p><strong>Background: </strong>Authorized COVID-19 vaccines require boosters for continued protection; however, the lack of cross-platform compatible boosters creates practical challenges to keeping populations protected.</p><p><strong>Methods: </strong>This Phase 3, multicenter, international, randomized, active-controlled trial compared UB-612 as a third-dose heterologous booster to BNT162b2, ChAdOx1-S, or BBIBP-CorV homologous boosters in healthy subjects aged ≥16 years. Participants were randomly assigned 1:1 to receive a single intramuscular injection of UB-612 or an active comparator matching the primary dose, and were stratified for age, sex, N-protein seropositivity, and time since the last dose of their primary series COVID-19 vaccination. The primary objective was to show non-inferiority of neutralizing antibody geometric mean titer (GMT) against live SARS-CoV-2 Wuhan strain after boosting with UB-612 or each of the licensed platform vaccines. Secondary and exploratory objectives covered short and long-term antibody responses. The safety analysis addressed subject and investigator reported adverse events. The study was registered on ClinicalTrials.gov, NCT05293665, and completed on September 12, 2023.</p><p><strong>Findings: </strong>Between March 22 and September 9, 2022, 469 subjects received UB-612 as a heterologous booster, and 467 received BNT162b2 (n = 204), ChAdOx1-S (n = 95), or BBIBP-CorV (n = 168) as homologous boosters. Over 90% of all subjects were positive for N-protein antibody at baseline. When compared to the respective homologous booster response, UB-612 stimulated Wuhan and Omicron BA.5 neutralizing antibody responses that were non-inferior, thus meeting all primary and secondary immunogenicity endpoints of the study. Importantly, UB-612 demonstrated superiority in neutralizing antibody GMT and seroresponse rates compared to ChAdOx1-S and BBIBP-CorV. UB-612 was also effective in stimulating neutralizing antibodies against a more recent Omicron XBB1.5 strain. Long-term immunity analysis through 6- and 12-month follow-ups favored UB-612 over ChAdOx1-S and BBIBP-CorV and supported comparable immunity to BNT162b2. All vaccines were well tolerated and had similar safety profiles.</p><p><strong>Interpretation: </strong>In a pivotal Phase 3 study, UB-612 demonstrated the potential for broad use as a cross-platform heterologous booster, restoring protective immunity in adults previously vaccinated with mRNA, adenovirus-vectored, or inactivated virus-based COVID-19 vaccines.</p><p><strong>Funding: </strong>The study was co-funded by the Coalition for Epidemic Preparedness Innovations (CEPI) and Vaxxinity.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103349"},"PeriodicalIF":10.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of tranexamic acid on blood coagulation in primary total hip arthroplasty using rotational thromboelastometry: a randomized controlled trial.","authors":"Uzung Yoon, David Beausang, Elia Elia, Marc Torjman, Jeffrey Mojica, James Purtill, David Nazarian, P Maxwell Courtney, Yoogoo Kang","doi":"10.1016/j.eclinm.2025.103374","DOIUrl":"10.1016/j.eclinm.2025.103374","url":null,"abstract":"<p><strong>Background: </strong>Tranexamic acid (TXA), is commonly administered prophylactically to reduce blood loss in patients undergoing total hip arthroplasty (THA). However, its effect has never been studied. We hypothesized that no difference exists in the degree of fibrinolysis and blood loss between patients receiving prophylactic TXA and placebo.</p><p><strong>Methods: </strong>This double-blinded randomized-controlled trial included 50 patients undergoing primary THA in 2021-2023. Clinicaltrials.gov (NCT03897621). Rotational-thromboelastometry (ROTEM) were performed to test blood coagulability using non citrated whole blood (NATEM) and blood treated with TXA (T-APTEM). The intervention group received TXA intravenously. The placebo group received 0.9% sodium chloride solution. The primary outcome measure was to quantitate the degree of fibrinolysis measured by maximum lysis (ML) demonstrated by ROTEM variables. Fibrinolysis was defined as ML (maximum lysis) > 15% within 1 h of testing.</p><p><strong>Findings: </strong>Blood coagulability tested by ROTEM was within the normal range in all patients, and no difference was found between the TXA group and placebo group.NATEM and T-APTEM variables were similar in both groups and no patient developed fibrinolysis during the entire perioperative phases. At baseline, T-APTEM, compared with NATEM, showed shorter CT (746 ± 265 vs. 991 ± 237 p < 0.05) and greater ML (1.9 ± 2.2 vs. 0.8 ± 1, p < 0.05), suggesting some degree of acceleration of coagulation. Postoperatively, blood coagulability showed a tendency of acceleration with shorter CT (689 ± 188 vs. 828 ± 163, p < 0.05) and CFT (258 ± 101 vs. 293 ± 87 p < 0.05) and increased A10 (41 ± 9 vs. 38 ± 8, p < 0.05). Clinical outcomes, including blood loss, hematologic variables, and coagulation profile were similar between the two groups.</p><p><strong>Interpretation: </strong>Normal range of blood coagulability in all patients, no significant differences between NATEM and T-APTEM variables, and similar clinical outcome between the two groups suggest that there is no definitive medical indication for TXA administration in patients undergoing THA without a preexisting fibrinolytic condition. Monitoring blood coagulability using ROTEM may be useful in guiding selective administration of TXA in high-risk patients.</p><p><strong>Funding: </strong>Department of Anesthesiology funding, Thomas Jefferson University Hospital. Support was provided solely from institutional and/or departmental sources.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103374"},"PeriodicalIF":10.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741636","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":"De-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer (NJMU-BC01): a multicenter, single-arm, phase 2 trial.","authors":"Hong Pan, Yi Ren, Mengyao Zha, Mingduo Liu, Xiaoan Liu, Hui Xie, Xiaoming Zha, Yi Zhao, Lin Chen, Tiansong Xia, Zhao Liu, Jing Tao, Hua Pan, Yue Sun, Wei Li, Cong Wang, Qiang Ding, Shui Wang, Wenbin Zhou","doi":"10.1016/j.eclinm.2025.103376","DOIUrl":"10.1016/j.eclinm.2025.103376","url":null,"abstract":"<p><strong>Background: </strong>Due to the undesirable cumulative toxicity of multiple drugs, de-escalated neoadjuvant chemotherapy strategies are needed for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Pyrotinib, a small-molecule irreversible pan-HER receptor tyrosine kinase inhibitor, shows promising efficacy in the neoadjuvant setting. We aimed to determine the efficacy, safety and predictive biomarkers of the de-escalated neoadjuvant nab-paclitaxel combined with pyrotinib and trastuzumab in intrinsic HER2-enriched breast cancer.</p><p><strong>Methods: </strong>In this multicenter phase 2 study (NCT05659056), patients who were histologically diagnosed with HER2-positive breast cancer (clinical stage ⅡA-ⅢC) were deemed suitable to participate in this study. Participants received pyrotinib (400 mg once), trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg maintenance dose), and nab-paclitaxel (260 mg/m²) on day 1 of each 3-week cycle for six cycles. The primary endpoint was the rate of total pathological complete response (tpCR) among BluePrint HER2-enriched breast cancers, which was defined as complete disappearance of invasive tumor in breast specimen and all sampled axillary lymph nodes (ypT0/is, ypN0). This study has been completed.</p><p><strong>Findings: </strong>Between 3 December 2022 and 6 June 2024, 74 participants were finally enrolled in the study. Of all enrolled participants, 66 had baseline BluePrint and MammaPrint results. Among the 43 participants with BluePrint HER2-enriched breast cancer, 23 achieved tpCR (53%, 95% CI 38%-69%), and 28 achieved breast pathological complete response (bpCR) (65%, 95% CI 49%-79%). Among the 23 participants with non-HER2-enriched subtypes, 7 achieved tpCR (30%, 95% CI 13%-53%), while 10 achieved bpCR (43%, 95% CI 23%-66%). Of 66 participants with MammaPrint risk score index, the tpCR rate in MammaPrint ultra-high group (24/39) was significantly higher than that in high group (6/27, <i>P</i> = 0.0024). With the median follow-up of 19.9 months (IQR, 15.5-25.4), no cases of recurrence, metastasis, or mortality events were observed. Grade 3-4 treatment-related adverse events occurred in 17 (23%) participants. The most common grade 3-4 adverse event was diarrhea (10/74). No treatment-related deaths occurred. Of all enrolled participants, no treatment discontinuations occurred due to disease progression during the neoadjuvant therapy period.</p><p><strong>Interpretation: </strong>De-escalated neoadjuvant cytotoxic chemotherapy regimen is promising for BluePrint HER2-enriched breast cancer. Our results provide critical references for the efficacy and biomarkers of de-escalated neoadjuvant therapy in HER2-positive breast cancer.</p><p><strong>Funding: </strong>National Natural Science Foundation of China and Natural Science Foundation of Jiangsu Province.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103376"},"PeriodicalIF":10.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728670","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":"Comparative safety and efficacy of oncolytic virotherapy for the treatment of individuals with malignancies: a systematic review, meta-analysis, and Bayesian network meta-analysis.","authors":"Poyee Lau, Long Liang, Xiang Chen, Jianglin Zhang, Hong Liu","doi":"10.1016/j.eclinm.2025.103362","DOIUrl":"10.1016/j.eclinm.2025.103362","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Oncolytic virotherapy (OV) is an innovative immunotherapy strategy. A comprehensive understanding of oncolytic viruses is essential for advancing research and clinical practice. This analysis aims to evaluate the clinical outcomes of oncolytic virotherapy in cancer patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed single-arm, pairwise, and Bayesian network meta-analyses, incorporating clinical trials identified through PubMed, Medline, Embase, and the Cochrane Library from database inception to April 30, 2025. Primary endpoints included all-grade and grade ≥3 adverse events (AEs), objective response rate (ORR), and disease control rate (DCR). Effect size measures included risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) or credible intervals (CrIs). Subgroup analyses were conducted to assess outcomes, and meta-regression was applied to evaluate the influence of prognostic variables. This study is registered with PROSPERO, number CRD42022306458.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Of 1976 studies screened, 186 clinical trials with 6979 participants met the inclusion criteria. The most common adverse events associated with oncolytic virotherapy were fatigue (1.98%, 1.71-2.28), pyrexia (2.16%, 1.69-2.69), fever (3.32%, 2.64-4.07), and chills (1.65%, 1.39-1.82), with neutropenia (1.07%, 0.67-1.55) and lymphocytopenia (0.71%, 0.51-0.94) being the predominant severe adverse events. While oncolytic virus monotherapy (OV vs immunotherapy, DCR 2.45, 95% CI 1.60-3.76) and combination regimens (OV plus chemotherapy vs OV, DCR 8.53, 95% CI, 1.97-37.03) enhanced therapeutic efficacy, they presented higher toxicity risks compared to conventional treatments (OV vs immunotherapy, all-grade AE 2.07, 95% CI 1.75-2.44). Notably, combination therapies involving chemotherapy (OV plus chemotherapy vs chemotherapy, all-grade AE 1.10, 95% CI 1.02-1.18) or radiotherapy (OV plus radiotherapy vs radiotherapy, all-grade AE 1.53, 95% CI 1.27-1.84) significantly increase adverse event risks. Conversely, oncolytic virotherapy combined with immunotherapy showed a more favorable safety profile (OV plus immunotherapy vs OV plus chemotherapy, severe AE 0.32, 95% CrI 0.15-0.66) and clinical benefits (OV plus immunotherapy vs OV plus chemotherapy, DCR 0.08, 95% CrI 0.02-0.33). Efficacy varied significantly across treatment strategies (adjusted &lt;i&gt;p&lt;/i&gt; = 0.040), virus classifications (adjusted &lt;i&gt;p&lt;/i&gt; = 0.0027), administration routes (adjusted &lt;i&gt;p&lt;/i&gt; = 0.0080), and patient age groups (adjusted &lt;i&gt;p&lt;/i&gt; = 0.00080).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;This analysis provides robust evidence on the tolerability and efficacy of oncolytic virotherapy in cancer treatment. Oncolytic virotherapy demonstrates significant potential as both monotherapy and in combination regimens, offering a favorable balance of efficacy and safety. Virotherapy paired with immunotherapy exhibits a more favorable safety profile, particularly in re","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103362"},"PeriodicalIF":10.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728669","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 expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions.","authors":"Areesha Moiz, Kristian B Filion, Michael A Tsoukas, Oriana H Y Yu, Tricia M Peters, Mark J Eisenberg","doi":"10.1016/j.eclinm.2025.103363","DOIUrl":"10.1016/j.eclinm.2025.103363","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed obesity management, offering substantial weight loss and metabolic benefits. This review examines their expanding role, evaluating efficacy compared to alternative treatments, emerging indications, ongoing challenges, and future directions. Beyond obesity and type 2 diabetes, the therapeutic potential of GLP-1 RAs extends to a range of conditions such as cardiovascular disease, liver disease, neurodegenerative disease, and substance abuse disorders. While early concerns regarding pancreatic and thyroid cancer have been largely attenuated by recent evidence, issues such as gallbladder and biliary disorders, psychiatric safety, and perioperative aspiration risk require ongoing investigation. Additionally, observations of weight regain after treatment discontinuation and reductions in lean mass highlight the need for long-term, individualized strategies to sustain clinical benefits. The high cost and limited access to these medications raise critical policy and equity challenges. Future research must address these gaps, focusing on long-term safety, optimizing combination approaches, and evaluating the broader clinical and economic implications of widespread GLP-1 RA use.</p><p><strong>Funding: </strong>K.B.F. is supported by a William Dawson Scholar award from McGill University. T.M.P. is a Fond de Recherche du Québec-Santé (FRQS) research scholar. M.J.E. holds a James McGill Professor award from McGill University. The funding sources had no involvement in the conduct of this study, interpretation of results, or the preparation of this manuscript for publication.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103363"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728685","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":"Optimal timing and mode of planned birth for term, large infants: a retrospective, population-based cohort study.","authors":"Georgia Anne Santomartino, Kylie Crawford, Jesrine Hong, Sailesh Kumar","doi":"10.1016/j.eclinm.2025.103366","DOIUrl":"10.1016/j.eclinm.2025.103366","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Large infants (birthweight &gt; 75th centile) are at increased risk of mortality, severe neonatal neurological and non-neurological morbidity. We aimed to ascertain the optimal method and gestation of planned birth (scheduled caesarean section or induction of labor) that were associated with lower odds of adverse outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This was a retrospective cohort study of term singleton births with birthweight &gt;75th centile between January 2000 and December 2021 in Queensland, Australia. Primary outcomes were severe adverse maternal outcome, perinatal mortality (intrapartum stillbirth or neonatal death), severe neonatal neurological morbidity, and other severe neonatal morbidity. Multivariable logistic regression models were built to determine odds ratios (OR) for the effect of timing of both methods of planned birth on adverse outcomes. Induction of labor at 38&lt;sup&gt;+0&lt;/sup&gt;-38&lt;sup&gt;+6&lt;/sup&gt; weeks was the referent category because many international guidelines recommend this as the optimum timing of birth.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;There were 151,464 planned births for large infants. 86,515 (57.1%) were induction of labor while 64,949 (42.9%) were scheduled caesarean section. Compared to induction of labor at 38&lt;sup&gt;+0&lt;/sup&gt;-38&lt;sup&gt;+6&lt;/sup&gt; weeks, induction at ≥41&lt;sup&gt;+0&lt;/sup&gt; weeks (aOR 1.28, 95% CI 1.21, 1.35) and scheduled caesarean section at 37&lt;sup&gt;+0&lt;/sup&gt;-37&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 1.18, 95% CI 1.08, 1.28) were associated with greater odds of severe adverse maternal outcome, whilst scheduled caesarean section at 39&lt;sup&gt;+0&lt;/sup&gt;-39&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 0.75, 95% CI 0.70, 0.80) was associated with lower odds of this outcome. The odds of severe neonatal neurological morbidity were lower following induction at 40&lt;sup&gt;+0&lt;/sup&gt;-40&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 0.72, 95% CI 0.59, 0.89) or scheduled caesarean section at 37&lt;sup&gt;+0&lt;/sup&gt;-37&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 0.59, 95% CI 0.43, 0.81), 39&lt;sup&gt;+0&lt;/sup&gt;-39&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 0.26, 95% CI 0.2, 0.33), and ≥41&lt;sup&gt;+0&lt;/sup&gt; weeks (aOR 0.31, 95% CI 0.13, 0.75) respectively. For other severe neonatal morbidity, the odds were highest after induction of labor at 37&lt;sup&gt;+0&lt;/sup&gt;-37&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 1.35, 95% CI 1.24, 1.46), and lowest following scheduled caesarean section at 40&lt;sup&gt;+0&lt;/sup&gt;-40&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 0.31, 95% CI 0.26, 0.36). There were no significant differences in perinatal mortality based on method of planned birth or gestational age.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;In our cohort, scheduled caesarean section between 39&lt;sup&gt;+0&lt;/sup&gt;-39&lt;sup&gt;+6&lt;/sup&gt; weeks for large infants at birth was associated with lower odds of severe adverse maternal outcomes, severe neonatal neurological morbidity, and other severe neonatal morbidity compared to induction of labor at 38&lt;sup&gt;+0&lt;/sup&gt;-38&lt;sup&gt;+6&lt;/sup&gt; weeks. For women that underwent induction of labor, the odds of emergency caesarean section were lowest at 39&lt;sup&gt;+0&lt;/sup&gt;-39&lt;sup&gt;","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103366"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728683","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":"Timing of intravenous iron for treatment of anaemia in surgical patients: a systematic review and network meta-analysis.","authors":"Chang Liu, Jiashu Han, Renkui Fu, Tianyu Li, Georgios Antonios Margonis, Jaeyun Jane Wang, Kaiqi Ma, Weibin Wang, Chen Lin","doi":"10.1016/j.eclinm.2025.103361","DOIUrl":"10.1016/j.eclinm.2025.103361","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Anaemia complicates recovery in surgical patients. Intravenous (IV) iron supplementation shows promise in improving outcomes, but optimal timing remains uncertain. In this review, we compare the efficacy, safety, tolerability, and outcomes between preoperative and postoperative IV iron supplementation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this systematic review and network meta-analysis, we searched PubMed, EMBASE, Cochrane Library, and Web of Science from inception to May 1, 2025, for randomised controlled trials (RCT) investigating IV iron supplementation in surgical patients either 7-30 days before surgery (preoperative) or 0-30 days after surgery (postoperative). Studies were excluded if they included patients with critical illness or prior transfusion or if iron was given outside the defined time frames or with other agents. Two reviewers independently appraised the data and extracted summary estimates from published reports. The primary outcomes were: (1) proportion of patients who received blood transfusion; (2) change between the baseline haemoglobin level and the haemoglobin level on postoperative day (POD) 7 and POD30. Data processing was conducted based on frequentist network meta-analysis. The risk of bias was assessed using the Cochrane Risk of Bias tool. The protocol is registered with PROSPERO, CRD42024533265.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Among 129 identified studies, 22 RCTs with 3026 patients were included. All included studies had a low (n = 6) or moderate (n = 16) risk of bias. Compared to controls, postoperative IV iron supplementation reduced transfusion rates (RR 0.80, 95% CI 0.68-0.94; I&lt;sup&gt;2&lt;/sup&gt; = 0.0%). Postoperative IV iron supplementation did not affect haemoglobin levels (MD -4.51, 95% CI -9.75 to 0.72; I&lt;sup&gt;2&lt;/sup&gt; = 90.3%) at POD7 but increased haemoglobin levels (MD 5.45, 95% CI 2.70-8.20; I&lt;sup&gt;2&lt;/sup&gt; = 45.5%) at POD30. In comparison, preoperative IV iron supplementation resulted in higher haemoglobin levels than postoperative supplementation at POD30 (MD 6.67, 95% CI 1.61-11.72) but did not influence transfusion rates (RR 0.91, 95% CI 0.72-1.15; I&lt;sup&gt;2&lt;/sup&gt; = 0.0%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Our results suggest that postoperative IV iron supplementation reduces transfusion rates, while preoperative supplementation improves haemoglobin recovery. Clinicians may choose either strategy in an individualised, patient-centered manner. These conclusions should be interpreted with caution due to heterogeneity among included studies, limited data for subgroup analyses, and the absence of direct comparisons between preoperative and postoperative approaches.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;National Key Research and Development Program of China, National Natural Science Foundation of China, Beijing Natural Science Foundation, Capital's Funds for Health Improvement and Research, National High Level Hospital Clinical Research Funding, and Chinese Academy of Medical Sciences I","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103361"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728686","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":"Development and validation of a novel prognostic model to predict 1-year post-transplant mortality for acute-on-chronic hepatitis B liver failure: a nationwide, multicentre, cohort study.","authors":"Li Zhuang, Yimou Lin, Yu Jia, Jun Fang, Yujian Zheng, Taishi Fang, Meiching Ong, Aibo Mu, Jiaxing Zhu, Mengchao Wang, Dong Zhao, Feiwen Deng, Qiucheng Lei, Leibo Xu, Zuozhong Yang, Qiang Sun, Wei Qu, Chenwei Xu, Zhijun Zhu, Chuanjiang Li, Hanyu Jiang, Jimin Liu, Xiaoshun He, Shusen Zheng, Zhiyong Guo, Qi Ling","doi":"10.1016/j.eclinm.2025.103365","DOIUrl":"10.1016/j.eclinm.2025.103365","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Liver transplantation (LT) provides a potential cure for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop and externally validate a prognostic model to predict 1-year post-LT mortality in patients with HBV-ACLF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This retrospective, nationwide, observational cohort study was conducted at ten high-volume LT centres in China. 4378 adult patients who underwent primary LT between January 2015 and December 2021 were screened, and those with HBV-ACLF according to the COSSH-ACLF criteria (separated into three ACLF grades based on the number of organ failures) were included. The HBV-ACLF LT (HALT) model was developed in the derivation cohort and validated in the external testing cohort. The derivation cohort were derived from two LT centres in one province (Zhejiang). The external testing cohort were derived from eight LT centres in two provinces. For model development, univariable Cox regression analysis was used to identify risk factors associated with 1-year post-LT mortality. Variables with univariable &lt;i&gt;p&lt;/i&gt; &lt; 0.05 were entered into the least absolute shrinkage and selection operator (Lasso) analysis for further feature selection. 10-fold cross validation was used to choose the optimal lambda (penalty for the number of features) of the Lasso model. Multivariable Cox regression was applied to construct the HALT model based on the risk factors selected by Lasso analysis. Primary outcome was survival rate at 1-year after LT. Secondary outcomes were short-term (28- and 90-day) and long-term survival after LT (3- and 5-year). Model performance was compared with eight other models (COSSH-ACLF II, COSSH-ACLF, CLIF-C ACLF, AARC, MELD, MELD-Na, SALT-M and TAM scores), using receiver operating characteristic curve and C-index values. A nomogram was developed to analyse the probability of the primary outcome in different graft-recipient combinations based on recipient factors (age, number of organ failures [OF], lactate) and graft factors (donation after circulatory death [DCD] and cold ischaemia time [CIT]).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between Jan 1, 2015, and Dec 1, 2021, 668 patients were included (derivation cohort, n = 418; external testing cohort, n = 250), with survival rates of 88.0%, 81.1%, 77.5%, 75.6% and 72.1% at 28-day, 90-day, 1-year, 3-year and 5-year post-LT, respectively. Three recipient's factors (age, number of OF and arterial lactate concentration) as well as two graft's parameters (DCD and CIT) were independently associated with 1-year post-LT mortality in the derivation cohort (all &lt;i&gt;p&lt;/i&gt; &lt; 0.05). The HALT model was established accordingly, showing better discriminative performance (C-index, 0.791) than eight current models in the external testing cohort (C-index, 0.529-0.627; all &lt;i&gt;p&lt;/i&gt; &lt; 0.001). If the sickest patients (age &gt;55 years, OFs ≥3 and lactate ≥2.5 mmol/L) received high-risk grafts (DCD and CIT &gt;10 h), the estimate","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103365"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728671","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":"Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysis.","authors":"C A Smith, S Y Bögli, M M Placek, M Cabeleira, D White, E Daubney, A Young, E Beqiri, R Kayani, R O'Donnell, N Pathan, S Watson, A Maw, M Garnett, H K Kanthimathinathan, H Bangalore, S Sundararajan, G Subramanian, D Raffaj, S Lampariello, A Sarfatti, A Mayer, O Ross, M Czosnyka, P J Hutchinson, P Smielewski, S Agrawal","doi":"10.1016/j.eclinm.2025.103370","DOIUrl":"10.1016/j.eclinm.2025.103370","url":null,"abstract":"<p><strong>Background: </strong>Cerebral perfusion pressure (CPP) represents a key target for intensive care management of paediatric traumatic brain injury (TBI) patients. Current guidelines recommend a CPP target within the range of 40-50 mmHg but emphasise that these may depend on patient age and the state of cerebrovascular autoregulation. In this analysis, we aimed to compare the fixed targets proposed by the Brain Trauma Foundation to autoregulation-based targets CPPopt (optimal CPP) and LLA (Lower Limit of Autoregulation).</p><p><strong>Methods: </strong>Data were acquired from the STARSHIP study (a prospective, multicentre, observational, research study which enrolled 135 children (median age 96 months (interquartile range 26-152 months)) with TBI between July 2018 and March 2023 across 10 paediatric intensive care units in the UK). In this secondary analysis the dose or percentage time spent below a fixed CPP target of 50 mmHg or CPPopt or LLA (assessed continuously on a minute-by-minute basis and derived by fitting a curve to the relationship between CPP and pressure reactivity index values, as previously described) was compared by outcome using univariable and multivariable methods. ClinicalTrials.gov registration-NCT0688462.</p><p><strong>Findings: </strong>When assessed within ordinal analyses (to account for differences in baseline severity), both hourly dose and percentage time spent below LLA (odds ratio 1.01 [95% CI 1.00-1.02], p = 0.017 and 1.05 [95% CI 1.01-1.08], p = 0.008 respectively) were independently associated with worse outcomes. LLA displayed a dynamic time-trend increasing over time in patients with unfavourable outcome (n = 44, p = 0.003). Overall, LLA exceeded 50 mmHg for more than 45% of the monitoring period across all patients, and for over 35% of the time in the youngest cohort (0-2 years).</p><p><strong>Interpretation: </strong>Dynamic autoregulation monitoring based on LLA was associated with outcomes in paediatric TBI with higher LLA values observed in individuals experiencing unfavourable outcomes. Our findings indicate that the current fixed CPP threshold of 40-50 mmHg may be too low-highlighting the need for further investigation into autoregulation-guided CPP targets. Whether personalised management based on autoregulatory-informed thresholds offers advantages over guideline-based targets remains to be determined and should be investigated in future prospective interventional studies.</p><p><strong>Funding: </strong>Action Medical Research for Childrens' Charity and Addenbrookes Charitable Trust (UK Grant number-GN2609).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103370"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728681","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 personalized neoadjuvant therapy selection strategies in breast cancer: an explainable multi-modal response model.","authors":"Luyi Han, Tianyu Zhang, Anna D'Angelo, Anna van der Voort, Katja Pinker-Domenig, Marleen Kok, Gabe Sonke, Yuan Gao, Xin Wang, Chunyao Lu, Xinglong Liang, Jonas Teuwen, Tao Tan, Ritse Mann","doi":"10.1016/j.eclinm.2025.103356","DOIUrl":"10.1016/j.eclinm.2025.103356","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant therapy (NAT) regimens for breast cancer are generally determined according to cancer stage and molecular subtypes without fully considering the inter-patient variability, which may lead to inefficiency or overtreatment. Artificial intelligence (AI) may support personalized regimen recommendations by learning the synergistic relationship between pre-NAT individual-patient data, regimens, and corresponding short- or long-term therapy responses.</p><p><strong>Methods: </strong>In this retrospective study, we collected data from breast cancer patients treated with NAT between 2000 and 2020 from the Netherlands and the USA. Median follow-up times ranged from 3·7 to 4·9 years across molecular subtypes and cohorts. We developed and externally validated a multi-modal model integrating pre-NAT clinical data, dynamic contrast enhanced (DCE)-MRI images, and medical reports to predict pathological complete response (pCR) and likelihood of survival after NAT. We subsequently evaluated potential benefits for patients receiving a personalized regimen recommended based on these predictions.</p><p><strong>Findings: </strong>We trained our model on 655 patients and validated it on internal (655 patients) and external (241 patients) cohorts. Given the factual regimens, the model can correctly predict the corresponding therapy response, with areas under the receiver operating characteristic curves (AUC) of 0·80 (95% CI 0·73-0·87), 0·75 (0·66-0·83), and 0·85 (0·77-0·92) for pCR prediction of human epidermal growth factor receptor 2 (HER2)+, triple-negative, and estrogen receptor/progesterone receptor (ER/PR)+&HER2- patients in the internal validation cohort, respectively. Performance in the external validation cohort was 0·707 (0·557-0·836), 0·558 (0·359-0·749), and 0·860 (0·767-0·945) for the corresponding molecular subtypes, respectively. In the internal validation cohort, survival prediction identified high-risk patients across different molecular subtypes, as demonstrated by a hazard ratio (HR) of 3·29 (0·91-11·94) (HER2+), 3·54 (1·52-8·20) (triple-negative), and 2·78 (1·45-5·31) (ER/PR+&HER2-), albeit results were not significant for HER2+ cancers.</p><p><strong>Interpretation: </strong>Our findings indicate that the prognostic scores generated by the response model could identify patient subgroups with relatively poor outcomes under their actual treatments. These preliminary findings may inform future efforts toward personalized NAT regimen selection beyond traditional criteria such as cancer stage and subtype, but should be interpreted cautiously and validated in prospective studies with longer follow-up because these tumors can relapse at a later stage.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103356"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728682","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}