EClinicalMedicine最新文献

{"title":"Laboratory evaluation of 185 commercial assays for detecting SARS-CoV-2: the UK response for mass testing.","authors":"Abbie Bown, Tim Peto, Angela Sweed, Matthew Catton, Joshua Nelthorpe-Cowne, Tracy Benford, Tom Collinge, Donna Robinson, Louise Oliver, Susan Hopkins, Derrick Crook, Somya Agrawal, Hannah Fordham, Tom Fowler, Alex Sienkiewicz, Ann Sarah Walker, Sir John Bell, Richard Vipond","doi":"10.1016/j.eclinm.2025.103416","DOIUrl":"10.1016/j.eclinm.2025.103416","url":null,"abstract":"<p><strong>Background: </strong>In August 2020, Public Health England and Oxford University were commissioned to design and deliver (with NHS Test and Trace, NHSTT) a rapid evaluation programme of antigen Lateral Flow Devices (LFDs) for SARS-CoV-2 for mass community testing.</p><p><strong>Methods: </strong>A three-phase evaluation process was established: 1) desktop review of kits including claimed performance and supply; 2) laboratory testing with laboratory-grown SARS-CoV-2 virus and SARS-CoV-2 virus PCR negative volunteer samples; and 3) larger-scale laboratory testing of SARS-CoV-2 PCR positive and negative clinical samples. Variant of Concern (VOC) identification in the UK (December 2020), expanded laboratory methodology. Processes also evolved to improve workflow (irradiated viral stocks, dilution matrices, sample volumes, and replicates).</p><p><strong>Findings: </strong>Overall, 1017 kits were screened at phase 1, 185 kits tested at phase 2 and 91 at phase 3. Sixteen kits failed phase 3 due to poor performance and eight more failed to detect VOC satisfactorily. Sixty-four kits were redesigns of previously failed kits. The overall pass rate for the laboratory evaluation was 35% and 5 kits were procured for the UK National Covid 19 Testing Programme.</p><p><strong>Interpretation: </strong>The evaluation results had potential, time limited commercially sensitive aspects, and public sharing was limited to kits passing phase 3. Until now, the full data set has not been published. Over 2.5 billion self-test kits were deployed by the UK government following purchasing decisions informed by this work. We offer a potential blueprint for future evaluation programmes that might be required to assess LFDs to detect cases of a pandemic novel pathogen.</p><p><strong>Funding: </strong>This study was funded by UK Department of Health and Social Care (UKHSA); UK Health Security Agency (formerly Public Health England and the National Health Service Test and Trace); and the University of OxfordNIHRBiomedical Research Centre.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103416"},"PeriodicalIF":10.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238243","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":"Osimertinib plus consolidative radiotherapy for advanced <i>EGFR</i> mutant non-small cell lung cancer: a multicentre, single-arm, phase 2 trial.","authors":"Sagus Sampath, Sawsan Rashdan, Puneeth Iyengar, Townes A Mickel, Song Zhang, Chul Ahn, Ang Gao, Jonathan E Dowell, Yuanyuan Zhang, Kenneth D Westover, Suzanne M Cole, Arya Amini, Adam Rock, Erminia Massarelli, Marianna Koczywas, David E Gerber","doi":"10.1016/j.eclinm.2025.103435","DOIUrl":"10.1016/j.eclinm.2025.103435","url":null,"abstract":"<p><strong>Background: </strong>Despite high response rates to epidermal growth factor receptor (EGFR) inhibitors, patients with advanced <i>EGFR</i> mutant non-small cell lung cancer (NSCLC) generally experience disease progression within 2 years. We evaluated whether consolidative radiation therapy (RT) to residual sites of disease at the time of expected best response to EGFR inhibition prolongs disease control.</p><p><strong>Methods: </strong>This multicentre, single-arm phase 2 trial was conducted at two sites in the USA. Eligible patients (aged ≥18 years) had advanced <i>EGFR</i> mutant (exon 19 or 21) NSCLC not restricted by number, site, or size of metastases; ECOG 0-2; and no prior treatment with EGFR or immune checkpoint inhibitors. Patients with stable or responding disease after 8 weeks of osimertinib 80 mg orally daily received radiation therapy (RT) to persisting lesions, followed by continued osimertinib until progression or intolerance. The primary endpoint was progression-free survival (PFS) in all participants who received at least one dose of osimertinib, assessed radiographically every 8 weeks. Secondary endpoints were toxicity, duration on osimertinib, and overall survival (OS). This trial is registered with Clinicaltrials.gov, NCT03667820.</p><p><strong>Findings: </strong>Between Oct 15, 2018, and July 1, 2021, 42 patients (32 female, 10 male) were enrolled and initiated osimertinib, of whom 32 (76%) received consolidative RT, primarily stereotactic RT. The most common reasons RT was not administered were insufficient residual disease (10%) and inadequate response (5%). At a median follow-up of 35.7 months, median PFS was 32.3 months (95% CI, 21.9-51.7), median OS was 45 months (95% CI, 39.3-56.4), and median duration of osimertinib was 32.4 months. Osimertinib-related toxicities, including skin, nail, and gastrointestinal events, occurred at expected rates and were almost always grade 1-2. Two patients (5%) developed pneumonitis, including one grade 4 event.</p><p><strong>Interpretation: </strong>These findings show osimertinib plus consolidative RT was well tolerated and demonstrates promising efficacy in patients with advanced <i>EGFR</i> mutant NSCLC. Because this approach may be less complex and less toxic than multi-agent targeted therapy regimens for this population, the results of ongoing randomised trials testing similar strategies are awaited.</p><p><strong>Funding: </strong>AstraZeneca and the Biostatistics Shared Resource, UT Southwestern Harold C. Simmons Comprehensive Cancer Center.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103435"},"PeriodicalIF":10.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238318","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":"Incidence of suicide within two years of a first diagnosis of depression, anxiety, or mixed anxiety and depression: an exploratory cohort study in primary care using the Clinical Practice Research Datalink.","authors":"James Bailey, Patricia Schartau, Seena Fazel, Irwin Nazareth, Irene Petersen","doi":"10.1016/j.eclinm.2025.103441","DOIUrl":"10.1016/j.eclinm.2025.103441","url":null,"abstract":"<p><strong>Background: </strong>The risk of suicide following first diagnosis of depression or anxiety in primary care is uncertain. We investigated suicide incidence within two years of a first diagnosis of depression, anxiety, or mixed anxiety and depression in primary care, analysing variation by diagnosis, age, sex, and social deprivation at lower layer Super Output Area level.</p><p><strong>Methods: </strong>We conducted a cohort study using the Clinical Practice Research Datalink, a large primary care electronic health records database, linked to mortality records. Adults with their first diagnosis of depression, anxiety, or mixed anxiety and depression between 1 January 1999 and 31 December 2018 were included. The outcome was suicides per 100,000 person-years at risk (PYAR) within two years of diagnosis. Adjusted incidence rate ratios (aIRR) were calculated using Poisson regression.</p><p><strong>Findings: </strong>Among 1,454,102 individuals diagnosed there were 1439 suicides within two years of diagnosis. Rates were higher in men across all cohorts. The highest rate for men was after depression diagnosis: 115·85 per 100,000 PYAR (95% confidence interval [CI] 107·60-124·58), five times higher than women: aIRR 4·99 (95% CI 4·29-5·79). For women the highest rate was after a mixed diagnosis: 27·73 per 100,000 PYAR (95% CI 21·70-34·92). The highest rate across all groups was seen in men aged 70+ after a mixed diagnosis: 156·43 per 100,000 PYAR (95% CI 89·41-254·03). There was no association between rate and deprivation.</p><p><strong>Interpretation: </strong>Suicide rates within two years of a diagnosis were higher than the UK general population rate as reported by the Office for National Statistics. Men consistently exhibited higher rates, with men aged 70 and over diagnosed with mixed anxiety and depression experiencing the highest rate. Women aged 50-59 with a first diagnosis of anxiety had over three times the rate of those aged 18-29 at diagnosis. These findings align with findings from other settings and add to the literature by quantifying the effects in primary care. Further analysis is required, particularly for older men and middle-aged women with anxiety-related conditions.</p><p><strong>Funding: </strong>James Bailey is funded by a National Institute for Health and Care Research Doctoral Fellowship [NIHR302551].</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103441"},"PeriodicalIF":10.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238227","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":"Streptococcal endocarditis: a meta-analysis of species dependant risk.","authors":"Gavin Deas, Todd C Lee, Julia Colston, Mahableshwar Albur, Julia Vasant, Angela H Nobbs, Philip Williams, Fergus Hamilton","doi":"10.1016/j.eclinm.2025.103425","DOIUrl":"10.1016/j.eclinm.2025.103425","url":null,"abstract":"<p><strong>Background: </strong>Streptococcal infective endocarditis (IE) is a devastating disease. In international guidance, the risk of IE from streptococci is considered the same regardless of species (excluding <i>Streptococcus pyogenes</i> and <i>Streptococcus pneumoniae</i>). However, the idea of homogenous risk has been recently questioned. We aimed to evaluate the risk of IE across streptococcal species through meta-analysis of other published works and our own local data.</p><p><strong>Methods: </strong>We first conducted a scoping review for publications that reported cases of streptococcal bacteraemia differentiated by species and estimated the risk of IE between 1994 and October 2024. Then we supplemented this data with our own laboratory data from four large hospitals. We meta-analysed the risk of IE. Two sensitivity analyses were performed to deal with one manuscript which excluded cultures considered as contaminants: first, by excluding that publication, and second by adjusting for blood culture contamination using our local estimated contamination rates.</p><p><strong>Findings: </strong>Four studies met inclusion criteria comprising a total of 14,183 isolates with 1028 endocarditis cases (7.25% absolute risk of IE). The highest risk species were: <i>Streptococcus mutans</i>: 47% (95% CI 38-56%), <i>Streptococcus cristatus</i>: 41% (95% CI 21-62%), <i>Streptococcus gordonii</i>: 37% (95% CI 30-44%), <i>Streptococcus sanguinis</i> 33% (95% CI 28-39%), and <i>Streptococcus gallolyticus</i>: 31% (95% CI 27-36%). Combined, these species accounted for only 8.4% of bacteraemias but 38.6% of IE. The most common IE pathogen overall was <i>Streptococcus mitis/oralis</i> (23.6% of IE, 8% of bacteraemias) but these infections themselves only carried an IE risk of 12% (95% CI 11-13%). There was strong evidence of heterogeneity detected in <i>S. mitis/oralis</i> (I² 87%; Cochran's Q: 30 p: <0.001) and <i>S. gallolyticus</i> (I² 90%; Q: 29 p: <0.001).</p><p><strong>Interpretation: </strong>The 'small five' streptococci: <i>S. mutans, S. cristatus, S. gordonii, S. gallolyticus,</i> and <i>S. sanguinis</i> account for only 8% of all streptococcal bloodstream infections but nearly 40% of all streptococcal IE with a risk of IE in individual infections as high as ∼50%. The risk of <i>S. mitis/oralis</i> appears heterogeneous, may depend on species or subspecies, and requires further study.</p><p><strong>Funding: </strong>FH was funded by the NIHR Clinical Lectureship Scheme. TL has salary support from Fonds de Recherche Québec - Santé. PW is funded by a Medical Research Council grant MR/T005408/1.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103425"},"PeriodicalIF":10.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238232","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":"Letting happiness happen.","authors":"eClinicalMedicine","doi":"10.1016/j.eclinm.2025.103467","DOIUrl":"10.1016/j.eclinm.2025.103467","url":null,"abstract":"","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103467"},"PeriodicalIF":10.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946874","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 efficacy of Cyclosporine A in recurrent spontaneous abortion: a meta-analysis and network meta-analysis incorporating Chinese and English language studies.","authors":"Xianyang Hu, Xixi Huang, Tingxuan Yin, Hailin Yu, Lu Liu, Meirong Du","doi":"10.1016/j.eclinm.2025.103442","DOIUrl":"10.1016/j.eclinm.2025.103442","url":null,"abstract":"<p><strong>Background: </strong>Recurrent spontaneous abortion (RSA) poses a significant clinical challenge for childbearing women. Cyclosporine A (CsA), first introduced by our group for RSA treatment, has gained wide clinical application in China, yet remains underutilized internationally. With this systematic review, we aimed to systematically evaluate the efficacy and safety of CsA based therapy in the management of RSA.</p><p><strong>Methods: </strong>PubMed, Embase, Web of Science, Cochrane library, CNKI, VIP, and Wanfang databases were searched from inception to July 12, 2025. Eligible studies in English and Chinese language, involved patients with RSA and assessed CsA's effects on pregnancy outcomes were included. Risk of bias was evaluated using appropriate tools based on study design. Pooled odds ratios (ORs) were calculated via meta-analysis. Publication bias was evaluated with funnel plots. Subgroup and network meta-analysis (NMA) were conducted to assess robustness and compare relative efficacy. Primary outcomes included miscarriage rate and live birth rate as reported in clinical pregnancy outcomes. This study was registered with PROSPERO (CRD42024541367).</p><p><strong>Findings: </strong>A total of 29 clinical studies (n = 3556 RSA patients) were included, with 22 comparing CsA-treated vs non-CsA-treated groups. The majority of studies were conducted in a Chinese population (28 = China, and 1 = Iran) as CsA therapy for RSA has not received approval outside of China. CsA therapy was associated with a lower miscarriage rate (OR, 0.37 [95% CI, 0.25-0.56]), higher live birth rate (OR, 37 2.44 [95% CI, 1.59-3.74]), and higher ongoing pregnancy rate (OR, 2.59 [95% CI, 1.54-38 4.37]). NMA revealed that CsA combined with conventional treatment, and immunotherapy (P-score: 0.147-0.275) had superior effects on miscarriage reduction compared to monotherapy (P41 score: 0.619-0.792). CsA-based combinations also remained superior to monotherapies (P-score: 0.704-0.791 vs 0.27-0.305). However, for live birth rate, the combination of conventional treatment and immunotherapy showed the greatest efficacy (P-score: 0.892).</p><p><strong>Interpretation: </strong>This meta-analysis demonstrates the potential benefits of CsA therapy for pregnancy outcomes in RSA patients, particularly when combined with other therapeutic interventions. These findings require further multi-center prospective testing at an international level.</p><p><strong>Funding: </strong>This study was supported by the National Natural Science Foundation of China (NSFC), the National Key R&D Program of China, the Shanghai Municipal Health and Family Planning Commission, and the Shanghai Sailing Program.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103442"},"PeriodicalIF":10.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946469","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":"Arterial and venous thromboembolic events in patients with cancer treated with targeted therapies: a population-based cohort study.","authors":"Florian Moik, Erzsébet Horváth-Puhó, Cihan Ay, Ingrid Pabinger, Frits Mulder, Nick van Es, Henrik Toft Sørensen","doi":"10.1016/j.eclinm.2025.103440","DOIUrl":"10.1016/j.eclinm.2025.103440","url":null,"abstract":"<p><strong>Background: </strong>Emerging data suggest a substantial risk of arterial and venous thromboembolic events (ATE/VTE) associated with targeted cancer therapies. We examined the association between selected targeted therapies and ATE/VTE-risk using Danish population-based healthcare data.</p><p><strong>Methods: </strong>We identified 41,744 patients with cancer treated with selected targeted therapies between January 2004 and December 2020. We computed cumulative incidence functions and 95% confidence intervals (CIs) of ATE/VTE after therapy initiation, considering death as competing event. A multivariable Cox proportional hazards regression analysis with time-varying exposure to targeted therapy was conducted for selected cancers, calculating hazard ratios (HRs) and 95% CIs for ATE/VTE, enabling the comparison of the time periods with and without targeted therapy, adjusting for age, sex, comorbidity burden, cancer stage, and year of diagnosis.</p><p><strong>Findings: </strong>The three-year cumulative ATE-incidence was 3.7% (95% CI: 3.2-4.2) with immune checkpoint inhibitors (ICI; n = 7880), 3.4% (95% CI: 2.8-4.1) with multi-kinase inhibitors (MKI; n = 3394), 2.6% (95% CI: 1.9-3.5) with cyclin dependent kinase (CDK) 4/6-inhibitors (n = 1966), 2.5% (95% CI: 1.0-5.4) with anaplastic lymphoma kinase (ALK)-/ROS1-targeted therapies (n = 199), 2.6% (95% CI: 2.2-2.9) with epidermal growth factor receptor (EGFR)-targeted therapies (n = 8603), 2.4% (95% CI: 2.1-2.7) with vascular endothelial growth factor (VEGF)-targeted therapies (n = 12,802), and 1.4% (95% CI: 1.2-1.6) with human epidermal growth factor receptor 2 (HER2)-targeted therapies (n = 11,683). The three-year VTE-incidence was highest for EGFR- (9.3% [95% CI: 8.7-9.9]), ALK/ROS- (9.2% [95% CI: 5.7-13.8]), VEGF-targeted therapies (8.8% [95% CI: 8.3-9.3]), and ICI (8.1% [95% CI: 7.5-8.8]), followed by 7.5% (95% CI: 6.7-8.5) with MKI, 6.9% (95% CI: 5.7-8.3) with CDK4/6-inhibitors, and 3.4% (95% CI: 3.1-3.8) with HER2-targeted therapies. Among patients with selected cancer types, time-dependent exposure to certain targeted therapies was associated with an increased risk of ATE and/or VTE.</p><p><strong>Interpretation: </strong>Selected targeted therapies pose a clinically meaningful risk of ATE and VTE in patients with cancer.</p><p><strong>Funding: </strong>Department of Clinical Epidemiology, Center for Population Medicine, Aarhus University and Aarhus University Hospital, Denmark and the Independent Research Fund Denmark (3101-00102B).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103440"},"PeriodicalIF":10.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946811","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":"Dose-optimised recombinant human thrombopoietin <i>versus</i> eltrombopag in patients with immune thrombocytopenia: a multicenter, randomised controlled trial (The TE-ITP Study).","authors":"Yunfei Chen, Ting Sun, Da Gao, Wei Wang, Zeping Zhou, Guangxun Gao, Yi Wang, Hu Zhou, Yanping Song, Yinghui Lai, Zhenyu Yan, Jinsong Yan, Jie Bai, Lei Zhang","doi":"10.1016/j.eclinm.2025.103459","DOIUrl":"10.1016/j.eclinm.2025.103459","url":null,"abstract":"<p><strong>Background: </strong>Recombinant human thrombopoietin (rhTPO) at a fixed dose of 300 U/kg/day for 2 weeks has demonstrated good efficacy and safety in adults with immune thrombocytopenia (ITP). This trial aimed to develop a flexible and personalized rhTPO regimen that ensures efficacy and safety beyond previous fixed dose, with eltrombopag as an active comparator.</p><p><strong>Methods: </strong>The TE-ITP trial was conducted in 12 centers across China. Adult ITP patients with platelet count <30 × 10⁹/L were randomised (2:1) to receive rhTPO or eltrombopag. The initial dose in patients with baseline platelet count of 20-30 × 10⁹/L <i>versus</i> <20 × 10⁹/L was 300 <i>versus</i> 600 U/kg/day for rhTPO and 25 <i>versus</i> 50 mg/day for eltrombopag, respectively. Dosage was adjusted weekly according to platelet count, with maximum of 600 U/kg/day for rhTPO and 75 mg/day for eltrombopag. The primary endpoint was the time to first platelet count ≥50 × 10⁹/L. The trial is registered on ClinicalTrials.gov (NCT05583838).</p><p><strong>Findings: </strong>Between November 22, 2022 and January 16, 2024, the trial enrolled 157 patients (median age: 52 years; 104 women): 105 and 52 in the rhTPO and eltrombopag groups, respectively. Baseline platelet count was <20 × 10⁹/L in 57.1% (60/105) and 57.7% (30/52) in the rhTPO and eltrombopag groups, respectively. The median time to the first platelet count ≥50 × 10⁹/L was 7 days (95% CI 6.0-7.0) in the rhTPO group <i>versus</i> 15 days (95% CI 9.0-25.0) in the eltrombopag group (<i>p</i> < 0.001). The risk of bleeding was lower in the rhTPO group (OR 0.523, 95% CI 0.360-0.758; <i>p</i> < 0.001). Adverse events occurred in 45.7% (48/105) and 60.8% (31/52) in the rhTPO and eltrombopag groups, respectively.</p><p><strong>Interpretation: </strong>The optimised rhTPO regimen, with individualized dosing based on platelet response, showed faster platelet elevation and lower bleeding risk than eltrombopag.</p><p><strong>Funding: </strong>This trial was supported by grants from the CAMS Innovation Fund for Medical Sciences (CIFMS) (2023-I2M-2-007), Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0500803), National Natural Science Foundation of China (82430010), Tianjin Municipal Science and Technology Commission Grant (24ZXZSSS00230).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103459"},"PeriodicalIF":10.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946888","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":"Supplemental parenteral nutrition within an enhanced recovery program for open pancreatoduodenectomy for cancer: a pragmatic, multicenter, randomized controlled trial.","authors":"Luca Gianotti, Salvatore Paiella, Giovanni Capretti, Nicolò Pecorelli, Isabella Frigerio, Marta Sandini, Alessandro Fogliati, Eleonora Vico, Marco Braga, Christian Cotsoglou, Alfonso Pedalino, Giuseppe Malleo, Simone Ricchitelli, Sabrina Caspani, Giovanni Guarneri, Alessia Vallorani, Alessandro Giardino, Elettra Pasqualoni, Roberto Salvia, Alessandro Zerbi, Massimo Falconi, Giovanni Butturini, Davide Paolo Bernasconi","doi":"10.1016/j.eclinm.2025.103455","DOIUrl":"10.1016/j.eclinm.2025.103455","url":null,"abstract":"<p><strong>Background: </strong>The role of supplemental parenteral nutrition (SPN) following pancreatoduodenectomy (PD) in the context of an enhanced recovery program is unexplored. This study aimed to determine whether SPN is superior to early oral feeding alone in reducing postoperative complications.</p><p><strong>Methods: </strong>This pragmatic, multicenter, randomized controlled, trial, across five centers in Italy, enrolled patients aged 18-89 years undergoing open PD for cancer. We excluded patients with an American Society of Anaesthesiology physical status >3 and a preoperative body weight loss of ≥15%. Patients were randomly assigned (1:1) postoperatively to either SPN from day 1 to 5 or no-SPN. All patients were free to begin oral feeding after the operation as desired in the context of a full enhanced recovery after surgery (ERAS) program. The primary outcome was morbidity burden, measured using the comprehensive complication index (CCI). Secondary outcomes included the overall rate of morbidity. Outcomes were assessed up to 90 days postoperatively. Overall, 120 patients per group were required to achieve 80% power and detect at least 30% reduction in the CCI in the SPN group, which was expected to be 23 (median) (interquartile range 21-31). The expected complication rate was 60%, and the type I error rate was set at 5%. Registration at ClinicalTrials.gov (#NCT04438447).</p><p><strong>Findings: </strong>From June 1, 2022, to December 20, 2023, 405 patients were screened for eligibility and 254 patients were randomly allocated to control (no-SPN; n = 129) or treatment (SPN; n = 125) group. All patients were included in the primary and secondary outcome analysis according to the intent-to-treat principle. The median CCI was 20.9 in both arms (median difference 0 [95% CI: -1.07 to 1.7]). The proportion of patients with at least one complication (CCI >0) was similar in both groups [(29.6% vs 29.2%; risk difference 0.4 (95% CI -11.1 to 7.0)]. The overall 90-day morbidity was 67.4% and 63.2% in the no-SPN arm and SPN arm groups, respectively [risk difference -4.2 (95% CI -16.7 to 8.2)]. In high nutritional risk patients (nutritional risk score ≥3), SPN was not protective against the primary outcome when compared with low-risk patients [OR 1.16 (95% CI 0.71-1.91)].</p><p><strong>Interpretation: </strong>In an ERAS program emphasizing early postoperative oral feeding, SPN does not affect outcome measures, even in patients at high nutritional risk. However, these results do not apply to severely malnourished patients or with critical comorbidities.</p><p><strong>Funding: </strong>The Italian Society for Artificial Nutrition and Metabolism (SINPE) and Baxter Italia S.p.A (Rome, Italy).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103455"},"PeriodicalIF":10.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946396","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 an interpretable multi-task model to predict outcomes in patients with rhabdomyolysis: a multicenter retrospective cohort study.","authors":"Chunli Liu, Jie Shi, Fengjuan Wang, Duo Li, Yu Luo, Bofan Yang, Yunlong Zhao, Li Zhang, Dingwei Yang, Heng Jin, Jie Song, Xiaoqin Guo, Haojun Fan, Qi Lv","doi":"10.1016/j.eclinm.2025.103438","DOIUrl":"10.1016/j.eclinm.2025.103438","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Rhabdomyolysis (RM) is a complex clinical syndrome with heterogeneous progression patterns among patients of varying severity. Early and accurate prediction of acute kidney injury (AKI), disease severity, renal replacement therapy (RRT) requirements, and mortality risk is essential for timely identification of high-risk individuals, personalized treatment planning, and optimal allocation of healthcare resources. We aimed to develop and externally validate an interpretable multi-task machine learning (ML) model to predict four clinical outcomes in patients with rhabdomyolysis: AKI, disease severity, the need for RRT, and in-hospital mortality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a retrospective study using three data sources: the eICU Collaborative Research Database (eICU-CRD), the Medical Information Mart for Intensive Care IV (MIMIC-IV), and electronic medical records from four tertiary hospitals in China. Data from eICU-CRD and MIMIC-IV were combined to form the derivation cohort for model training and internal validation, while data from the Chinese hospitals served as the external validation cohort. We analyzed 1429 patients from 2008 to 2019 in the derivation cohort and 362 patients from 2016 to 2022 in the external validation cohort. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, based on serum creatinine levels and urine output. Twenty-two clinical features available within the first 24 h of admission were selected to develop the prediction models. Ten machine learning (ML) algorithms were applied to construct multi-task prediction models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). To improve interpretability, feature importance was assessed using the SHapley Additive exPlanation (SHAP) method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;1429 patients were included in the derivation cohort (69.4% developed AKI, 36.7% were classified as having severe disease, 12.1% required RRT, and 9.8% had in-hospital mortality). 362 patients were included in the external validation cohort (27.9% developed AKI, 25.7% had severe disease, 27.3% required RRT, and 4.1% had in-hospital mortality). Among all evaluated models, the random forest (RF) algorithm exhibited the highest overall discriminative performance across the four prediction tasks. Based on feature importance rankings, interpretable final models were developed for each task using the top five contributing features. These models demonstrated robust predictive accuracy for AKI, disease severity, RRT requirements, and in-hospital mortality, with AUCs and corresponding 95% confidence intervals (CIs) of 0.914 (0.875-0.944), 0.909 (0.869-0.940), 0.888 (0.844-0.921), and 0.823 (0.773-0.865) in the internal validation cohort, and 0.906 (0.871-0.934), 0.856 (0.815-0.890), 0.852 (0.811-0.887), and 0.832 (0.789-0.869) in the external validation cohort, respectively. To su","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103438"},"PeriodicalIF":10.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946919","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}