EClinicalMedicine最新文献

{"title":"Comments regarding \"Effects of therapeutic interventions on long COVID: a meta-analysis of randomized controlled trials\".","authors":"David Tuller","doi":"10.1016/j.eclinm.2026.103882","DOIUrl":"10.1016/j.eclinm.2026.103882","url":null,"abstract":"","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"95 ","pages":"103882"},"PeriodicalIF":10.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812247","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":"Oropouche virus: transmission, epidemiology, genetic diversity, and public health implications.","authors":"Lorenzo Subissi, James R Otieno, Christopher Ruis, Ingrid Rabe, Anurag Agrawal, Laith Jamal Abu-Raddad, Esam I Azhar, Martin Beer, Haroldo Bezerra, Leon Caly, Meera Chand, Ariamys Companioni, Tulio de Oliveira, Isabelle Dietrich, Christian Drosten, Pablo Duran, Nuno R Faria, Adeola Fowotade, Lionel Gresh, Baoying Huang, Jason Kindrachuk, Marion P G Koopmans, Bette Korber, Yee-Sin Leo, Placide Mbala-Kingebeni, Martina McMenamin, Nada M Melhem, Vincent J Munster, Bruno T D Nunes, Bas B Oude Munnink, Felipe G Naveca, Malik Peiris, Gustavo Palacios, Paola Resende, Angel Rodriguez, Senjuti Saha, Tadaki Suzuki, Andrea Vicari, Anne von Gottberg, Pragya Yadav, Jairo Mendez-Rico, Maria D Van Kerkhove, Diana P Rojas","doi":"10.1016/j.eclinm.2026.103871","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103871","url":null,"abstract":"<p><p>Historically endemic to parts of South America, Oropouche virus (OROV) has caused an estimated 500,000 infections since its discovery, with a marked geographic expansion beyond the Amazon basin into other regions of South America and the Caribbean since late 2023. This Review synthesises current evidence on OROV epidemiology, transmission dynamics, clinical manifestations, diagnostics, viral diversity, and public health impact, with the primary objective of identifying critical knowledge gaps and outlining priorities for surveillance, research, and control. Human transmission occurs primarily via <i>Culicoides paraensis</i> midges, while the competence of other vectors, the role of animal reservoirs in sustaining sylvatic transmission, and the contribution of vertical and sexual transmission remain incompletely understood. Although most infections are self-limiting, reports of neurological disease, Guillain-Barré syndrome, adverse pregnancy outcomes, and rare fatalities highlight uncertainties regarding pathogenicity, risk factors for severe disease, and long-term sequelae. The known teratogenicity of related Simbu serogroup orthobunyaviruses in animals further raises concerns about foetal risk in humans. Environmental change, expanding vector ranges, and viral evolution are likely contributing to outbreak emergence and geographic spread. Based on the available evidence, this review highlights priority gaps in epidemiological surveillance, diagnostics and genomic monitoring, vector competence and ecology, transmission pathways, and countermeasure development. Addressing these gaps through coordinated surveillance, improved laboratory capacity, targeted vector control, and focused research will be essential to mitigate the public health impact of OROV and reduce the risk of further spread.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"95 ","pages":"103871"},"PeriodicalIF":10.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765777","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":"Real-world comparison of brain [¹⁸F]FDG-PET imaging with CSF Alzheimer's disease biomarkers in a tertiary memory clinic setting.","authors":"Neus Rabaneda-Lombarte, João Pedro Ferrari-Souza, Johanna Celedon, Eduardo R Zimmer, Bradford C Dickerson, Steven E Arnold, Pia Kivisäkk, Alberto Serrano-Pozo","doi":"10.1016/j.eclinm.2026.103910","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103910","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;[&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET brain scan remains widely used in the evaluation of cognitive decline worldwide, however data on its diagnostic performance against gold-standard CSF Alzheimer's disease (AD) biomarkers are scarce. We aimed to assess the agreement between [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET findings and CSF AD biomarkers in a real-world tertiary memory clinic setting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Cross-sectional study of Mass General Brigham patients with cognitive concerns and available [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET imaging and CSF AD biomarkers between 01/01/2013 and 06/30/2025. [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET brain scan findings were categorized as \"Normal,\" \"Abnormal Inconclusive,\" \"Abnormal Not AD-like,\" or \"Abnormal AD-like,\" based on the narrative report. The CSF AD biomarker panel was classified as \"Not AD,\" \"Equivocal,\" or \"Consistent with AD\" following the lab report. [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET was compared with gold-standard CSF AD biomarkers using kappa agreement test and regression models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Among 360 eligible individuals, 151 had a CSF profile \"Consistent with AD,\" 136 \"Equivocal,\" and 73 \"Not Consistent with AD.\" The [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET showed an AD-like pattern in 73/151 (48.3%) of subjects with CSF \"Consistent with AD\" and was normal in 30/73 (41.1%) of those with CSF \"Not Consistent with AD.\" However, 19/151 (12.6%) of individuals with a CSF profile \"Consistent with AD\" had normal [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET scans (false negatives) whereas 8/73 (11.0%) of those with a CSF profile \"Not Consistent with AD\" had an AD-like [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET pattern (false positives), resulting in 0.48 sensitivity, 0.84 specificity, and 0.66 AUC of [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET report vs. gold-standard CSF AD biomarkers, and a fair agreement between both tests (κ = 0.334). An AD-like [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET pattern was strongly associated with a CSF \"Consistent with AD\" (OR = 4.81, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and a lower Amyloid-Tau Index (ATI; β = -0.43, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). By region, posterior cingulate gyrus glucose hypometabolism predicted both an AD-like [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET result (OR = 6.41, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) and a CSF profile \"Consistent with AD\" (OR = 2.48, &lt;i&gt;p&lt;/i&gt; = 0.0003), whereas frontal hypometabolism predicted a Not AD-like [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET result (OR = 5.90, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001) but also lower odds of a CSF \"Not Consistent with AD\" (OR = 0.41, &lt;i&gt;p&lt;/i&gt; = 0.0016).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;[&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET imaging demonstrated high specificity but limited sensitivity to identify AD as defined by CSF biomarker criteria. Although a report of a typical AD-like [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET pattern of glucose hypometabolism predicted a positive CSF AD biomarker panel, the agreement between [&lt;sup&gt;18&lt;/sup&gt;F]FDG-PET report and CSF AD biomarker results was only fair.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;NR-L was supported by a Research Fellowship from the Fundación Ramón Areces, Madrid (Spa","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"95 ","pages":"103910"},"PeriodicalIF":10.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765789","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":"Outcome measurement instruments for the core outcome sets on genital gender-affirming surgery: the GenderCOS project.","authors":"Matteo Angelini, Philippine J Roijer, Marleen S Vallinga, Thomas E Pidgeon, Aline Ceulemans, Alex Bakker, Brenda Carrière, Tina Rashid, James Bellringer, Javier Belinky, Marlon Buncamper, Shane D Morrison, Walter P Bouman, Tim C van de Grift, Mark-Bram Bouman, Margriet G Mullender","doi":"10.1016/j.eclinm.2026.103907","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103907","url":null,"abstract":"<p><strong>Background: </strong>Outcome assessment in genital gender-affirming surgery (gGAS) has long been a heterogenous practice. Although two core outcome sets (COS) for masculinizing and feminizing gGAS have been previously established, the absence of standardized and validated outcome measurement instruments (OMIs) limits consistent reporting. The second phase of the GenderCOS project aimed to identify, evaluate, and recommend OMIs to standardize outcome assessment and facilitate adoption of the COS in gGAS research, ultimately enabling comparability and evidence synthesis.</p><p><strong>Methods: </strong>The project followed the Core Outcome Measures for Effectiveness Trials (COMET) initiative standards and the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for selecting OMIs for a COS. Phase 2 of the GenderCOS project was conducted from September 2024 to June 2025. Potential OMIs were identified through systematic reviews: PROSPERO: CRD42022347400 (inception to September 2023) and CRD42020223430 (inception to November 2020), clinical guidelines, and international expert consultations. All instruments relevant to at least one core outcome underwent quality and feasibility assessment. Consensus on the most appropriate OMIs and essential supplementary information was achieved through an international consensus process involving professional experts across multiple disciplines.</p><p><strong>Findings: </strong>A total of 380 potential OMIs were identified through systematic searches. After domain- and COS- matching, 152 patient-reported outcome measures (PROMs) and 53 clinical OMIs were evaluated on quality and feasibility aspects. The consensus process among professional experts in gender-care, resulted in measurement recommendations for 19 of the 20 unique core outcomes. These recommendations endorse the use of validated PROMs for the included patient-reported outcomes (PROs) and adherence to existing clinical guidelines for clinical outcomes and adverse events. For the remaining outcome relating to feminizing gGAS, a measurement recommendation was made for the subgroup that underwent vaginoplasty only. Development of an OMI suitable for all feminizing gGAS is also recommended.</p><p><strong>Interpretation: </strong>The GenderCOS provides the first consensus-based standardized measurement framework for core outcomes in gGAS. Its modular structure and inclusion of validated instruments enable harmonized reporting, data synthesis and evidence-based improvement in gGAS research.</p><p><strong>Funding: </strong>None received.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"95 ","pages":"103907"},"PeriodicalIF":10.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765783","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":"\"Magical relief\": the effectiveness of three stages of a video-based magic intervention on distress and pain in children aged 9-11 years during HPV mass vaccinations-a cluster-randomized trial.","authors":"Anne W E Versluis, Edmond H H M Rings, Arno A W Roest, Victor Middelkoop, Nienke Vreeken, Andrea W M Evers, Henriët van Middendorp","doi":"10.1016/j.eclinm.2026.103876","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103876","url":null,"abstract":"<p><strong>Background: </strong>Vaccinations often elicit significant distress in school-aged children, which can impact pain perception and future medical experiences. This study examined the effects of three stages of a video-based magic intervention on self-reported distress and pain in children receiving HPV vaccinations.</p><p><strong>Methods: </strong>This cluster-randomized controlled trial randomized 412 children (aged 9-11 years) who received their first HPV vaccination at five mass-vaccination sites in The Netherlands. Based on vaccination date and time, children were assigned to one of four groups: 1. watching a magic trick video during the vaccination, 2. watching the trick with revelation of the secret, 3. watching the trick with revelation of the secret, followed by a brief post-vaccination video-training, and 4. a regular care control. Children completed questionnaires before (T0) and after (T1) the first vaccination in April 2024, and before the second vaccination six months later (T2) in September/October 2024. The primary outcome of child-reported distress was assessed at T0, T1, and T2 using the Facial Image Scale (FIS) and the short form of the State-Trait Anxiety Inventory (STAI-6). The study was preregistered on OSF (https://doi.org/10.17605/OSF.IO/5ASM9, registered April 4, 2024).</p><p><strong>Findings: </strong>All randomized participants were analyzed according to the intention-to-treat principle. Children in the combined magic-intervention groups (groups 1-3) reported less distress and lower pain after the first vaccination compared to the control group (group 4; distress: <i>p</i> < 0.0001, partial <i>η</i> ² = 0.11; pain: <i>p</i> = 0.0039, <i>η</i> ² = 0.02, 95% CI [0.002-0.058]). The most extensive magic intervention (group 3) showed the largest distress reduction as compared to all other groups (<i>p</i> < 0.0001). No significant differences in distress were observed preceding the second vaccination, indicating a lack of sustained effects.</p><p><strong>Interpretation: </strong>The video-based magic intervention reduced distress and pain immediately following the vaccination, with the largest effect found for the most elaborate intervention group involving active engagement. These findings suggest a promising, easily implementable intervention to improve children's vaccination experiences during mass vaccinations.</p><p><strong>Funding: </strong>LUMC Foundation (non-profit).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"95 ","pages":"103876"},"PeriodicalIF":10.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765681","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":"Metformin and epigenetic age in non-diabetic older people with HIV in Madrid (METFORAGING): a double-blind, randomised, placebo-controlled, pilot trial.","authors":"Cristina Marcelo-Calvo, Andrés Esteban-Cantos, Francisco Jurado, Rocío Montejano, Javier Rodríguez-Centeno, Lucía Gutiérrez-García, Alejandro de Gea-Grela, Patricia Martínez-Martín, Alejandro Díez Vidal, Rosa de Miguel, Carlos M Oñoro-López, Juan Carlos González, Luz Martín-Carbonero, José Ignacio Bernardino, Rocío Menéndez Colino, Noemí González Pérez de Villar, Berta Rodés, José Ramón Arribas","doi":"10.1016/j.eclinm.2026.103874","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103874","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Metformin is increasingly studied as a potential geroprotective agent in the general population. We aimed to test the efficacy and safety of metformin to improve epigenetic age in older, well-controlled, non-diabetic people living with HIV.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;METFORAGING was a single-centre, double-blind, randomised, parallel-group, placebo-controlled pilot trial. Non-diabetic participants living with HIV who were aged 50 years or older, virologically suppressed, on a stable antiretroviral regimen with undetectable viral load for at least 12 months, and had CD4&lt;sup&gt;+&lt;/sup&gt; T-cell counts &gt;500 cells/μL were recruited from the HIV clinic at La Paz University Hospital (Madrid, Spain). Participants were randomly assigned (1:1) to receive 850 mg oral metformin or matching placebo twice a day for 96 weeks. Participants, investigators, and outcome assessors were masked to treatment allocation. Study visits were conducted at baseline and at weeks 4, 8, 24, 48, 72, and 96. Adherence was evaluated at each visit through pill count and self-report. At baseline and week 96, whole-blood samples were used to calculate biological age across 11 epigenetic biomarkers: first-generation epigenetic clocks (Horvath's clock and Hannum's clock), second-generation epigenetic clocks (PhenoAge and GrimAge V2), principal component-derived epigenetic clocks (PC-Horvath, PC-Hannum, PC-PhenoAge and PC-GrimAge), a third-generation clock (DunedinPACE), and the DNA methylation-based estimator of blood telomere length (DNAmTL). The primary outcome was the adjusted between-group difference in epigenetic age acceleration (EAA) change measured by the PhenoAge clock at week 96 in the per-protocol population. Analyses were stratified by age, sex, baseline CD4 count, smoking status, statin treatment, and route of HIV transmission. The trial was registered with EudraCT, 2021-003299-15.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between March 2, and Oct 2, 2022, 55 individuals were screened, and 40 were randomly assigned to metformin (n = 19) or placebo (n = 21). Enrolment was closed at 40 participants because of slow recruitment, below the pragmatic target of 60 outlined in the study protocol. Median age was 56.4 years (IQR 53.0-60.8), 12 (30%) were female, and 35 (87.5%) self-identified as White. Mean adherence by pill count was 97.5% in both groups. 35 (87.5%) of 40 participants continued treatment to 96 weeks (n = 17 in the metformin group and n = 18 in the placebo group; per-protocol population). At week 96, the adjusted between-group difference (metformin vs. placebo) for PhenoAge EAA was -1.02 years (95% confidence interval [CI] -5.30 to 3.26; p = 0.627). 48 adverse events occurred in 16 (84%) of 19 participants who received metformin and 48 adverse events occurred in 19 (90%) of 21 participants who received placebo. In the metformin group, no serious adverse events were attributed to the medication and no deaths or hospitalisation occurred.&lt;/p&gt;&lt;p&gt;","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"95 ","pages":"103874"},"PeriodicalIF":10.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765767","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":"Hip displacement management in spinal muscular atrophy in the era of disease modifying therapies: a Delphi consensus study in the UK.","authors":"Maria I Vanegas, Giovanni Baranello, Fabian Norman-Taylor, Michail Kokkinakis","doi":"10.1016/j.eclinm.2026.103872","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103872","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by bi-allelic deletions or pathogenic variants in the &lt;i&gt;SMN1&lt;/i&gt; gene. SMA type 1 is the most severe form with early muscle weakness, failure to achieve motor milestones, and limited survival. Disease-modifying therapies (DMT) nusinersen, risdiplam, and onasemnogene abeparvovec, have improved survival and motor outcomes but have also created new challenges, including more complex orthopaedic care. Management of hip displacement in symptomatic children with SMA remains controversial, with approaches ranging from conservative to surgical. We aimed to conduct a Delphi consensus exercise in the United Kingdom (UK) to provide national guidance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This Delphi consensus process began in September 2023 and included two rounds involving 45 senior health care professionals (paediatric neurologists, orthopaedic surgeons, physiotherapists) and patient representatives from 19 leading paediatric neuromuscular centres in the UK. The consensus process focussed on the prevention and management of hip displacement in children with SMA, supported by the SMA REACH and SMA CARE Networks, the British Society for Surgery in Cerebral Palsy (BSSCP), and British Society for Children's Orthopaedic Surgery (BSCOS). Round 1 was performed online (August-September 2024) and included a questionnaire of 16 statements. The questionnaire was distributed through members of the SMA REACH Network and members of BSCOS and BSSCP. A representative member from the advocacy group SMA UK was also invited to participate. Round 2 was performed in a hybrid manner (combined online and in-person participation) and allowed for live voting, modification, and final approval of approved statements. Input from patient representatives also informed the discussion.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Of the 23 paediatric neuromuscular centres invited to participate, 19 centres agreed. Round 1 included 44 respondents voting on 16 statements, resulting in consensus (&gt;75% agreement) on six and rejection of three statements. Seven were included for Round 2 discussion. Following live voting among 45 respondents in Round 2, the final consensus included 13 approved statements addressing key aspects of hip and contractures management in SMA. The recommendations emphasise individualised, multidisciplinary assessments and proactive strategies to prevent hip dislocation, particularly in children with higher motor potential, while acknowledging the lack of current evidence and the need to collect long-term data. Key recommendations included timeline for radiographic hip surveillance, and orthopaedic approach to painful hips as well as muscle and joint contractures. The consensus highlights the importance of building upon the existing national database (SMA Reach UK registry) and of developing evidence-based guidelines for both conservative and surgical approaches. The potential role","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"95 ","pages":"103872"},"PeriodicalIF":10.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765825","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":"Fraction dose escalation of split-course concurrent chemoradiotherapy following induction chemo-immunotherapy in unresectable locally advanced oesophageal squamous carcinoma in China (GASTO-10102): a single-centre phase 1 study.","authors":"FangJie Liu, DaQuan Wang, GuangYu Luo, HaoTing Zhang, YiMei Liu, PengXin Zhang, Biao Xia, Yu SiTu, MengRu Wang, DongSheng Zhang, Yi Hu, JunYe Wang, Bo Qiu, Hui Liu","doi":"10.1016/j.eclinm.2026.103893","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103893","url":null,"abstract":"<p><strong>Background: </strong>The optimal fractionation patterns and safety of hypofractionated radiotherapy remain poorly defined in locally advanced oesophageal squamous cell carcinoma (LA-ESCC). We aimed to determine the maximum tolerated fraction dose (MTFD) of split-course concurrent chemoradiotherapy (CCRT) following induction chemo-immunotherapy in patients with LA-ESCC.</p><p><strong>Methods: </strong>In this phase 1 study, patients (aged 18-80 years) with unresectable, histologically confirmed LA-ESCC (stage T1-4, N0-3, M0-1 disease; ECOG 0-1) were enrolled from one site in China (Sun yat-sen University Cancer Center, Guangzhou, Guangdong). Eligible participants had no prior treatment with chemotherapy, radiotherapy, surgery, or immunotherapy for ESCC and no evidence of deep ulceration on baseline esophagoscopy. Enrolled participants received two cycles of induction albumin-bound paclitaxel (260 mg/m², d1), cisplatin (60 mg/m², d1), and toripalimab (240 mg, d1) every three weeks, followed by definitive split-course radiotherapy with oral capecitabine (1000 mg/m², twice daily on days 1-14 of each radiotherapy course). Radiotherapy was delivered in two courses separated by a 4-week break using volumetric modulated arc therapy. Three dose levels were evaluated sequentially in cohorts of six patients: level 1 (30 Gy in 10 fractions + 20 Gy in 10 fractions), level 2 (28 Gy in 7 fractions + 22 Gy in 10 fractions), and level 3 (25 Gy in 5 fractions + 25 Gy in 10 fractions). The primary endpoint was MTFD within 12 months after completion of CCRT. The primary endpoint and safety analysis were assessed in all patients who received any study treatment. The trial is registered with ClinicalTrials.gov, NCT06020885.</p><p><strong>Findings: </strong>Between Aug 31, 2023, and July 23, 2024, 18 patients were enrolled (n = 6 per dose), and all completed split-course CCRT per protocol. The MTFD was not reached, and dose level 3 was tolerable. The most common grade 3 toxicity was lymphopenia (72.2%), followed by esophagitis (11.1%). No grade 4 or 5 toxicities occurred. The objective response rate after induction therapy was 100%. After CCRT, the clinical complete response rate was 83.3%. With a median follow-up of 20.5 months, median progression-free and overall survival were not reached; 1-year rates were 88.9% and 94.4%, respectively.</p><p><strong>Interpretation: </strong>Fraction dose-escalated split-course CCRT following induction chemo-immunotherapy was feasible, well tolerated, and showed encouraging preliminary efficacy. Larger prospective studies are warranted.</p><p><strong>Funding: </strong>The National Key Research and Development Program of China and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"95 ","pages":"103893"},"PeriodicalIF":10.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765670","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":"Effectiveness and safety of selective internal radiation therapy using yttrium-90 glass microspheres for hepatocellular carcinoma: real-world results from the multi-center prospective PROACTIF cohort of 989 patients.","authors":"Boris Guiu, Clément Bailly, Eric Vibert, Ghoufrane Tlili, Denis Mariano-Goulart, Julien Edeline, Yann Touchefeu, Emmanuel Durand, Jean Frédéric Blanc, Julia Chalaye, Hélène Regnault, Antoine Bouvier, Geraldine Sergent, Christian Sengel, Stéphane Renaud, Agnès Rode, Claude Somma, Patrick Chevallier, Vincent Habouzit, Isabelle Brenot-Rossi, Anthony Dohan, Lambros Tselikas, Thierry DeBaère, Sylvain Manfredi, Arnaud Dieudonné, Kirk Fowers, Eveline Boucher, Binal Patel, Eric Vicaut, Etienne Garin","doi":"10.1016/j.eclinm.2026.103884","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103884","url":null,"abstract":"<p><strong>Background: </strong>Selective Internal Radiation Therapy with yttrium-90 (Y90) has been used for decades, yet guideline recommendations remain inconsistent. High-quality real-world data is needed to guide practice. The objectives of this study were to evaluate effectiveness, safety, and patient quality of life (QoL) with TheraSphere™ treatment in real-world clinical practice, and to identify clinical and dosimetric factors associated with survival.</p><p><strong>Methods: </strong>PROACTIF was a prospective, open label, non-interventional, all-comers cohort study that recruited patients who received Y90 glass microspheres (TheraSphere™) per local standard of care across 34 French sites (January 2019-January 2024). Co-primary endpoints were overall survival (OS) and QoL. Secondary endpoints included safety, conversion to surgery, and factors associated with OS. OS and time-to-deterioration in QoL (Functional Assessment of Cancer Therapy-Hepatobiliary) were assessed by Kaplan-Meier analysis. Adverse events were descriptively summarized using Common Terminology Criteria for Adverse Events, version 5. Trial registration: ClinicalTrials.gov Identifier, NCT04069468.</p><p><strong>Findings: </strong>Amongst 989 HCC patients, 13·3%/18·9%/57·9%/5·8% were Barcelona Clinic Liver Cancer (BCLC) A/B/C/D, respectively; 35·3% had portal-vein tumor thrombosis (PVT); 74·4% were treated using multicompartment dosimetry, and 53·6% with selective Y90 administration. Mean index lesion dose was 435·4 Gy. For all patients, median OS (mOS) [95% CI] was 21·8 months (M) [20·1-23·3]. mOS was 27·0 M [20·7-31·4] for BCLC B, 21·1 M [18·0-22·8] for BCLC C; 23·1 M [21·6-27·0] without PVT, 24·8 M [19·3-30·3] for patients with Vp1/Vp2; 16·8 M mOS for patients with a pretreatment absorbed dose to the index lesion <200 Gy versus 26·0 M with ≥200 Gy (p < 0·001); 19·7 M for <400 Gy and 30·7 M for ≥400 Gy (p < 0·001). After Y90, 106/989 (10·7%) underwent curative-intent surgery, resulting in a mOS of 48·6 M [40·6-not evaluable], versus 20·1 M [17·7-21·7] without surgery. Median time-to-deterioration in QoL was 10·6 M [9·6-11·7]. Serious adverse events occurred in 7·5% patients; serious treatment-related events in 3·7%.</p><p><strong>Interpretation: </strong>In this large real-world cohort, treatment with Y90 glass microspheres demonstrated favorable effectiveness and safety with meaningful outcomes, especially in PVT patients and following subsequent surgery. PROACTIF showed a strong dose-survival relationship as demonstrated in previous studies, and highlights the potential of a tumor absorbed dose ≥400 Gy to further increase survival. These findings support dosimetry-guided Y90 across all BCLC stages, and should inform future guideline recommendations.</p><p><strong>Funding: </strong>Boston Scientific Corporation.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"95 ","pages":"103884"},"PeriodicalIF":10.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765727","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":"Pre-pregnancy weight in Swedish women and the risk of gestational diabetes and subsequent type 2 diabetes-a population-based cohort study.","authors":"Jon Edqvist, Annika Rosengren, Demir Djekic, Christina E Lundberg, Karin Andréasson, Pigi Dikaiou, Martin Adiels, Maria Åberg, Naveed Sattar, Carmen Basic, Teresia Svanvik, Martin Lindgren, Erik Thunström","doi":"10.1016/j.eclinm.2026.103912","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.103912","url":null,"abstract":"<p><strong>Background: </strong>Obesity in young women is increasing. To which extent elevated pre-pregnancy overweight and obesity with and without gestational diabetes increase long-term risk of type 2 diabetes later in life has not been quantified.</p><p><strong>Methods: </strong>In a Swedish population-based cohort study we used data from the Swedish Medical Birth Registry in 1,153,074 primiparous women included in the registry between Jan 1, 1987 and Dec 31, 2019, with body mass index (BMI) at the first antenatal care visit as a proxy for pre-pregnancy weight to examine risk for gestational diabetes. We then compared women with gestational diabetes (n = 16,870) to age matched comparators (n = 81,862) and calculated hazards for developing type 2 diabetes identified from the National Diabetes registry over a median follow-up of 9 years.</p><p><strong>Findings: </strong>Among 1,153,074 women, 21,438 (1.9%) were diagnosed with gestational diabetes. Women with pre-pregnancy BMI > 35 kg/m² had an almost 10-fold risk of gestational diabetes compared to those with low-normal weight. Among women with gestational diabetes, the hazard of type 2 diabetes began to increase already at low- or normal weight, increasing nearly exponentially with rising BMI, while the increase in risk with increasing BMI among women without gestational diabetes was much less marked. No other social/pregnancy related factors improved the prediction of type 2 diabetes.</p><p><strong>Interpretation: </strong>Gestational diabetes serves as a stress test for developing type 2 diabetes, markedly amplifying risk in even women with normal pre-pregnancy weight, and with very high absolute rates in women with pre-pregnancy obesity. Future work should ascertain to which extent women with gestational diabetes have a structured follow-up after their pregnancy, and their subsequent prognosis.</p><p><strong>Funding: </strong>The Swedish Research Council; the Swedish governmental funding of clinical research (ALF); the Swedish Heart and Lung Foundation; and Diabetes Wellness.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"95 ","pages":"103912"},"PeriodicalIF":10.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765813","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}