EClinicalMedicine最新文献

{"title":"Mentorship in endocrinology training: a cross-sectional study of the United States and Europe.","authors":"David Toro-Tobon, Heather Billings, Anina F Peersen, Elizabeth J Atkinson, Antoan S Sojat, Ljiljana V Marina, Irina Bancos","doi":"10.1016/j.eclinm.2025.103377","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103377","url":null,"abstract":"<p><strong>Background: </strong>Mentorship is crucial for developing both scientific and professional competencies in medical training, yet its role in endocrinology training remains underexplored. We aimed to assess the prevalence of mentorship in endocrinology trainees, analyse demographic and training programme factors, and evaluate the impact of mentor characteristics on trainee outcomes.</p><p><strong>Methods: </strong>We conducted a cross-sectional study of endocrinology trainees in the United States and Europe (23 countries) between June 2023 to January 2024. Participants were recruited via professional societies, email lists, and social media. Those who had completed more than 7 years of training post-medical school or had missing data on duration of training were excluded. A structured online questionnaire was developed using validated mentorship competency tools and adapted for regional nuances to collect data on demographics, mentorship experiences, academic productivity, and well-being. The primary outcome assessed the prevalence of mentorship; secondary outcomes evaluated the associations between mentor characteristics and self-reported academic productivity, satisfaction within the mentorship relationship, and levels of burnout and stress. Univariable and multivariable logistic regression analyses were conducted.</p><p><strong>Findings: </strong>Between June 10, 2023, and January 1, 2024, 250 respondents (154 from the U.S. and 96 from Europe; 70.0% women, 64.4% White), 75.8% reported having a mentor. Significant regional differences emerged: U.S. trainees predominantly self-selected their mentors (69.7% vs. 23.1% in Europe) and reported less frequent interactions (monthly or less vs. more than weekly in Europe). Univariable analyses revealed that attributes such as active listening, inspirational guidance, and personalised career support were strongly linked to enhanced academic productivity, higher training satisfaction, and reduced burnout. In multivariable models, inspirational guidance was a significant predictor of academic productivity among U.S. trainees (94.4% vs. 35.3%, OR: 54.72, 95% CI: 4.7-2255.9), while in Europe, mentors facilitating strategic goal-meeting was associated with decreased burnout (77.8% vs. 40.0%, OR: 5.49, 95% CI: 1.1-33.7) and inspirational guidance with markedly improved mentorship satisfaction (90.7% vs. 28.6%, OR: 51.86, 95% CI: 2.2-1177.2).</p><p><strong>Interpretation: </strong>Though the design precludes causal inference, these findings underscore the universal benefits of mentorship in endocrinology training and highlight that targeted mentor competencies are key drivers of trainee success. Tailoring mentorship frameworks to regional training contexts may optimise academic productivity, training satisfaction, and overall well-being. Future longitudinal and qualitative studies are needed to clarify causal pathways and evaluate the effectiveness of tailored mentorship interventions.</p><p><strong>F","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103377"},"PeriodicalIF":10.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741634","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":"Therapeutic anti-cancer vaccines: a systematic review of prospective intervention trials for common hematological malignancies.","authors":"Darshi Shah, Veer Shah, Karan Shah, Prachi J Shah, Muatassem Alsadhan, Alyson Haslam, Vinay Prasad, Muzaffar H Qazilbash, Rajshekhar Chakraborty, Ghulam Rehman Mohyuddin","doi":"10.1016/j.eclinm.2025.103378","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103378","url":null,"abstract":"<p><strong>Background: </strong>This review comprehensively assesses all prospective trials on anti-cancer vaccines for common hematological malignancies by analyzing trial designs, endpoints, and whether these endpoints are met across these trials.</p><p><strong>Methods: </strong>We included onco prospective clinical trials involving therapeutic anti-cancer vaccines for hematological malignancies published up to May 2025. We excluded retrospective cohort studies, case reports, non-research opinion publications, and studies not related to hematological malignancies. Information sources: Embase, MEDLINE, Web of Science Core Collection, and ClinicalTrials.gov. All the included RCTs were assessed for bias using the Cochrane Handbook for Systematic Review of Interventions, version 6.2 and Cochrane risk-of-bias tool. Results were synthesized descriptively, using frequencies (%) and medians (interquartile range [IQR]). The study protocol utilized was recorded in the PROSPERO database (Registration ID. CRD42024504780).</p><p><strong>Findings: </strong>Out of 2856 studies screened, a total of 187 studies were included. The median sample size was 18 (IQR = 20), and 33/187 (18%) studies were randomized. Most utilized primary endpoints were translational and safety, of which the endpoint was met 65/81 (80%) and 51/74 (69%) of the time, respectively. In 35/187 (19%) of the total studies included, the primary endpoint was a clinical efficacy endpoint (PFS, OS, duration of remission, cancer response) of which, 11/35 (31%) of studies met their clinical primary endpoint. Of the 33 randomized studies, 24 measured a clinical endpoint as their primary endpoint. Besides BCG administration in AML, no vaccine trial met a clinical efficacy endpoint in a randomized trial. There was not a single instance in which a vaccine product demonstrated an improvement in overall survival. The risk of bias assessment for RCTs showed most studies at low or intermediate risk of bias.</p><p><strong>Interpretation: </strong>This systematic review of all therapeutic anti-cancer vaccine trials in common hematological malignancies shows that although vaccines generally demonstrate immunogenicity, they have mostly failed to show consistent anti-cancer activity. Limitations include a lack of quantitative synthesis due to heterogeneity of assessed interventions, small sample sizes in most studies, and a lack of clear endpoint description in some studies.</p><p><strong>Funding: </strong>None. PROSPERO Registration ID. CRD42024504780.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103378"},"PeriodicalIF":10.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741637","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":"Towards universal early screening for cerebral palsy: a roadmap for automated General Movements Assessment.","authors":"Alicia J Spittle, Peter B Marschik, Lars Adde, Nadia Badawi, Rachel Byrne, Arend F Bos, Alain Chatelin, John Coughlan, Francesca Fedeli, Andrea Guzzetta, Edmond S L Ho, Michelle J Johnson, Amanda Kwong, Alistair McEwan, Catherine Morgan, Anderson Mughogho, Deirdre M Murray, Silvia Orlandi, Colleen Peyton, Laura A Prosser, Anina Ritterband-Rosenbaum, Truyen Tran, Dajie Zhang, Elyse Passmore","doi":"10.1016/j.eclinm.2025.103379","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103379","url":null,"abstract":"<p><p>Cerebral palsy (CP) is the most common lifelong physical disability, affecting millions globally. Early detection and intervention are crucial for improving outcomes, yet many children are diagnosed late. The General Movements Assessment (GMA) is a highly accurate clinical tool for detecting infants at high probability of CP, but access to health professionals trained in the GMA limits its use. Artificial intelligence (AI) has the potential to automate the GMA, increasing accessibility worldwide. We established an interdisciplinary, international consortium for the purpose of developing a roadmap for the ongoing development and implementation of an AI-enabled GMA system for universal CP screening worldwide. The consortium included clinicians (children neurologists, paediatricians, neonatologists, allied health), researchers, engineers, computer scientists, legal experts, and individuals with lived experience, from around the globe (across Africa, Australia, Europe, and North America). The roadmap identifies the following steps and key requirements within: (1) development of standards for AI validation; (2) development of AI-GMA from large and diverse validation sets; (3) development of software tools and clinical pathways; (4) regulatory requisites; and (5) implementation. With the roadmap, AI-enabled screening for CP incorporating state-of-the-art technology can be made possible. Future work will require international collaboration to allow for scaling of data sets, refining automated solutions and translation into practice.</p><p><strong>Funding: </strong>Cerebral Palsy Foundation, Cerebral Palsy Alliance, European Union Born to Get There, the National Health and Medical Research Council.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103379"},"PeriodicalIF":10.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741638","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":"Safety, tolerability and clinical effects of rovunaptabin, also known as BC007 on fatigue and quality of life in patients with Post-COVID syndrome (reCOVer): a prospective, exploratory, placebo-controlled, double-blind, randomised phase IIa clinical trial (RCT).","authors":"Bettina Hohberger, Marion Ganslmayer, Thomas Harrer, Friedrich Kruse, Stefanie Maas, Tobias Borst, Ralph Heimke-Brinck, Andreas Stog, Thomas Knauer, Eva Rühl, Victoria Zeisberg, Adam Skornia, Alexander Bartsch, Armin Ströbel, Monika Wytopil, Caroline Merkel, Sophia Hofmann, Katja G Schmidt, Petra Lakatos, Julia Schottenhamml, Martin Herrmann, Christian Mardin, Jürgen Rech","doi":"10.1016/j.eclinm.2025.103358","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103358","url":null,"abstract":"<p><strong>Background: </strong>Rovunaptabin neutralises functional autoantibodies targeting G-Protein coupled receptors (GPCR-fAAbs), observed in patients with Post-COVID syndrome. As we hypothesise an improvement of PCS by rovunaptabin, the aim of reCOVer was to investigate safety, tolerability, and clinical effects of rovunaptabin in PCS patients.</p><p><strong>Methods: </strong>reCOVer is a prospective, exploratory, placebo-controlled, double-blind, randomised phase IIa clinical investigator initiated trial with 1350 mg rovunaptabin with additional cross-over at the Universitätsklinikum Erlangen, Germany. The trial was registered in EudraCT, 2022-001781-35. Screening was done between 21·11·2023 and 25·06·2024. Eligible participants (18-80 years) showed GPCR-fAAbs, at least 3/8 defined PCS symptoms persisting ≥3 months after COVID-19 and fatigue as major symptom. Participants were randomly assigned (1:1) to either receive rovunaptabin or placebo at day 0 (d0) and d48 with a follow-up of 28 days, respectively. Primary endpoint was the number of treatment emergent adverse events (TEAE) at d28 (co-primary endpoint: TEAE at d70); secondary endpoint focused on fatigue and quality of life.</p><p><strong>Findings: </strong>Thirty PCS patients were randomised and analysed. RCT analysis showed nine (rovunaptabin) and five TEAEs (placebo), yet without statistically significance (p = 0·1299; CI -14·80%; 63·02%); one serious adverse event, not related to treatment, was recorded. Rovunaptabin showed a neutralisation of GPCR-fAAb and a significant improvement of FACIT Fatigue Scale (effect size = 2·10, p = 0·0378), Bell score (effect size = 3·64, p = 0·0004), Fatigue Severity Scale (effect size = -2·66, p = 0·0088), and quality of life (4/8 items).</p><p><strong>Interpretation: </strong>As this proof-of-concept study showed effects on the patient-centred endpoint PCS and a good safety profil, subsequent studies are needed to confirm these results in a larger cohort.</p><p><strong>Funding: </strong>German Federal Ministry of Education and Research, German Research Foundation.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103358"},"PeriodicalIF":10.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741635","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":"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":"https://doi.org/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}