Pub Date : 2026-01-09eCollection Date: 2026-01-01DOI: 10.1016/j.eclinm.2025.103739
Win Min Han, Bastian Neesgaard, Michael Knappik, Matthias Cavassini, Irene A Abela, Alisa Timiryasova, Lauren Greenberg, Charlotte Martin, Cristina Mussini, Ferdinand Wit, Caroline Sabin, Antonella Castagna, Akaki Abutidze, Wafaa El-Sadr, Fabrice Bonnet, Mario Sarcletti, Christina Carlander, Anna Hachfeld, Nina Weis, Vani Vannappagari, Felipe P Rogatto, Lital A Young, Sean R Hosein, Lene Ryom, Kathy Petoumenos
Background: Data on cancer incidence and associated risk factors among women with HIV are limited. We investigated cancer burden among women with HIV.
Methods: We included all women ≥18 years from the two large multicentre observational cohort collaborations (D:A:D and RESPOND). The primary outcomes were incidence of all cancers, HPV-related and common individual cancers including breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL) from 2006 to 2021. Baseline was defined as the latest date of entry into local cohort enrolment and 1st January 2006 for D:A:D and 1st January 2012 for RESPOND. Participants were followed from baseline until the date of first cancer, final follow-up or administrative censoring-whichever occurred first. We assessed risk factors using multivariable Poisson regression by applying robust standard errors and determined a population attributable fraction (PAF) for key risk factors for cancers.
Findings: Among 17,512 women included, median age at baseline was 39.5 years (interquartile range, IQR 32.5-46.0). Over 141,404 person-years (PYS) and a median 9.2 (5.5-10.1) years of follow-up, 832 women were diagnosed with any cancer; incidence rate 5.9 (95% CI 5.5-6.4)/1000 PYS, 163 HPV-related cancers (1.1 [1.0-1.3]/1000 PYS), 150 breast cancers (1.1 [0.9-1.2]/1000 PYS), 94 lung cancers (0.7 [0.5-0.8]/1000 PYS) and 72 NHL (0.5 [0.4-0.6]/1000 PYS). Older age (≥45 vs. <45 years), Southern Europe (vs. Western Europe) and smoking were associated with an increased risk of overall cancers. Lower pre-ART nadir CD4, time-updated CD4, and a prior AIDS diagnosis were associated with lung- and HPV-related cancer. In PAF analysis, smoking and HIV-related factors such as lower current CD4, nadir CD4 and HIV viremia significantly contributed to cancer risk.
Interpretation: Our findings suggest that women with HIV older than 45 years, past or current immunosuppressed or current smokers could be candidates for intensified cancer screening and prevention.
Funding: The Highly Active Antiretroviral Therapy Oversight Committee, The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The Isabel Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.
背景:感染艾滋病毒的妇女中癌症发病率和相关危险因素的数据有限。我们调查了感染艾滋病毒的妇女的癌症负担。方法:我们纳入了来自两个大型多中心观察队列合作(D:A:D和response)的所有≥18岁的女性。主要结局是2006年至2021年间所有癌症、hpv相关和常见个体癌症(包括乳腺癌、肺癌和非霍奇金淋巴瘤(NHL))的发病率。基线定义为进入当地队列的最迟日期,D:A:D为2006年1月1日,response为2012年1月1日。参与者从基线开始被跟踪,直到第一次癌症,最后随访或行政审查,以先发生者为准。我们使用多变量泊松回归通过应用稳健标准误差评估危险因素,并确定癌症关键危险因素的人口归因分数(PAF)。结果:纳入的17512名女性中,基线年龄中位数为39.5岁(四分位数范围,IQR 32.5-46.0)。在141404人年(PYS)和中位9.2(5.5-10.1)年的随访中,832名女性被诊断患有任何癌症;发病率为5.9 (95% CI 5.5-6.4)/1000 PYS, 163例hpv相关癌症(1.1 [1.0-1.3]/1000 PYS), 150例乳腺癌(1.1 [0.9-1.2]/1000 PYS), 94例肺癌(0.7 [0.5-0.8]/1000 PYS), 72例NHL (0.5 [0.4-0.6]/1000 PYS)。年龄较大(≥45岁vs.解释:我们的研究结果表明,年龄大于45岁的女性艾滋病毒感染者、过去或现在的免疫抑制或现在的吸烟者可能是加强癌症筛查和预防的候选者。资助:高活性抗逆转录病毒治疗监督委员会、CHU St Pierre Brussels HIV队列、奥地利HIV队列研究、澳大利亚HIV观察数据库、荷兰国家HIV观察队列艾滋病治疗评估、布莱顿HIV队列、克罗地亚国家HIV队列、EuroSIDA队列、法兰克福HIV队列研究、格鲁吉亚国家艾滋病卫生信息系统、尼斯HIV队列、伊莎贝尔基金会、摩德纳HIV队列、PISCIS队列研究、瑞士HIV队列研究、瑞典InfCare HIV队列研究、皇家自由HIV队列研究、圣拉斐尔科学研究所、波恩大学医院HIV队列、科隆大学HIV队列、默克生命科学、ViiV医疗保健和吉利德科学。
{"title":"Cancer burden and risk factors among women with HIV: a multi-regional study from the D:A:D and RESPOND cohort collaborations.","authors":"Win Min Han, Bastian Neesgaard, Michael Knappik, Matthias Cavassini, Irene A Abela, Alisa Timiryasova, Lauren Greenberg, Charlotte Martin, Cristina Mussini, Ferdinand Wit, Caroline Sabin, Antonella Castagna, Akaki Abutidze, Wafaa El-Sadr, Fabrice Bonnet, Mario Sarcletti, Christina Carlander, Anna Hachfeld, Nina Weis, Vani Vannappagari, Felipe P Rogatto, Lital A Young, Sean R Hosein, Lene Ryom, Kathy Petoumenos","doi":"10.1016/j.eclinm.2025.103739","DOIUrl":"10.1016/j.eclinm.2025.103739","url":null,"abstract":"<p><strong>Background: </strong>Data on cancer incidence and associated risk factors among women with HIV are limited. We investigated cancer burden among women with HIV.</p><p><strong>Methods: </strong>We included all women ≥18 years from the two large multicentre observational cohort collaborations (D:A:D and RESPOND). The primary outcomes were incidence of all cancers, HPV-related and common individual cancers including breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL) from 2006 to 2021. Baseline was defined as the latest date of entry into local cohort enrolment and 1st January 2006 for D:A:D and 1st January 2012 for RESPOND. Participants were followed from baseline until the date of first cancer, final follow-up or administrative censoring-whichever occurred first. We assessed risk factors using multivariable Poisson regression by applying robust standard errors and determined a population attributable fraction (PAF) for key risk factors for cancers.</p><p><strong>Findings: </strong>Among 17,512 women included, median age at baseline was 39.5 years (interquartile range, IQR 32.5-46.0). Over 141,404 person-years (PYS) and a median 9.2 (5.5-10.1) years of follow-up, 832 women were diagnosed with any cancer; incidence rate 5.9 (95% CI 5.5-6.4)/1000 PYS, 163 HPV-related cancers (1.1 [1.0-1.3]/1000 PYS), 150 breast cancers (1.1 [0.9-1.2]/1000 PYS), 94 lung cancers (0.7 [0.5-0.8]/1000 PYS) and 72 NHL (0.5 [0.4-0.6]/1000 PYS). Older age (≥45 vs. <45 years), Southern Europe (vs. Western Europe) and smoking were associated with an increased risk of overall cancers. Lower pre-ART nadir CD4, time-updated CD4, and a prior AIDS diagnosis were associated with lung- and HPV-related cancer. In PAF analysis, smoking and HIV-related factors such as lower current CD4, nadir CD4 and HIV viremia significantly contributed to cancer risk.</p><p><strong>Interpretation: </strong>Our findings suggest that women with HIV older than 45 years, past or current immunosuppressed or current smokers could be candidates for intensified cancer screening and prevention.</p><p><strong>Funding: </strong>The Highly Active Antiretroviral Therapy Oversight Committee, The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The Isabel Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"91 ","pages":"103739"},"PeriodicalIF":10.0,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017991","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}
Pub Date : 2026-01-08eCollection Date: 2026-01-01DOI: 10.1016/j.eclinm.2025.103743
William Nkhono, Eva van Lieshout, Job Calis, Violet Naanyu, Mark Hoogendoorn, Kamija S Phiri, María Villalobos-Quesada
Background: Machine Learning (ML) can contribute to reducing child mortality and morbidity in low- and middle-income countries (LMICs), yet its development and clinical adoption remain unclear. This systematic review provides an overview of ML for hospitalised children in LMICs.
Methods: In June 2025, searches in five scientific databases and one scholarly search engine identified 26 eligible peer-reviewed studies using ML on hospitalised children under 18. Studies using only conventional statistics and perinatal data were excluded. Study quality and bias were assessed using PROBAST + AI. Descriptive statistics were used for data analysis. PRISMA reporting guideline was followed.
Findings: These studies were conducted in Asia (58%) and Sub-Saharan Africa (38%), mostly retrospective (62%), and predominantly used patient files (62%). The median sample size was 1291. Prognostic models dominated (69%), primarily targeting mortality (50%). Ensemble methods were most common (50%). The median AUROC was 0.81 (IQR 0.78-0.83). Most models were at a clinical Readiness Level 3-4 (81%). Barriers and facilitators related to data (65%, 34% respectively), implementation (50%, 77%), technology (31%, 42%), and human (19%, 35%) were reported.
Interpretation: We provided evidence of ML's promising performance for LMICs. Mortality prediction was the main focus. Arriving at clinical applications that benefit LMICs, requires investment in high-quality data and alignment to local (clinical) needs.
Funding: This project is part of the EDCTP2 programme (grant number RIA2020I-3294 IMPALA) supported by the European Union.
{"title":"Machine learning for predicting clinical outcomes of hospitalised children: a systematic review of applications in low- and middle-income countries.","authors":"William Nkhono, Eva van Lieshout, Job Calis, Violet Naanyu, Mark Hoogendoorn, Kamija S Phiri, María Villalobos-Quesada","doi":"10.1016/j.eclinm.2025.103743","DOIUrl":"10.1016/j.eclinm.2025.103743","url":null,"abstract":"<p><strong>Background: </strong>Machine Learning (ML) can contribute to reducing child mortality and morbidity in low- and middle-income countries (LMICs), yet its development and clinical adoption remain unclear. This systematic review provides an overview of ML for hospitalised children in LMICs.</p><p><strong>Methods: </strong>In June 2025, searches in five scientific databases and one scholarly search engine identified 26 eligible peer-reviewed studies using ML on hospitalised children under 18. Studies using only conventional statistics and perinatal data were excluded. Study quality and bias were assessed using PROBAST + AI. Descriptive statistics were used for data analysis. PRISMA reporting guideline was followed.</p><p><strong>Findings: </strong>These studies were conducted in Asia (58%) and Sub-Saharan Africa (38%), mostly retrospective (62%), and predominantly used patient files (62%). The median sample size was 1291. Prognostic models dominated (69%), primarily targeting mortality (50%). Ensemble methods were most common (50%). The median AUROC was 0.81 (IQR 0.78-0.83). Most models were at a clinical Readiness Level 3-4 (81%). Barriers and facilitators related to data (65%, 34% respectively), implementation (50%, 77%), technology (31%, 42%), and human (19%, 35%) were reported.</p><p><strong>Interpretation: </strong>We provided evidence of ML's promising performance for LMICs. Mortality prediction was the main focus. Arriving at clinical applications that benefit LMICs, requires investment in high-quality data and alignment to local (clinical) needs.</p><p><strong>Funding: </strong>This project is part of the EDCTP2 programme (grant number RIA2020I-3294 IMPALA) supported by the European Union.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"91 ","pages":"103743"},"PeriodicalIF":10.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017983","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}
Pub Date : 2026-01-08eCollection Date: 2026-01-01DOI: 10.1016/j.eclinm.2025.103733
Laura A V Marlow, Ninian Schmeising-Barnes, Jo Waller
Background: Understanding experiences of diagnostic investigation for any new screening modality is important to inform the development of pathways for future implementation. We explored experience of diagnostic work-up within the NHS in people with a cancer signal detected result from a blood-based multi-cancer early detection (MCED) screening test in the NHS-Galleri trial (NCT05611632).
Methods: A subset of 41 participants with a cancer signal detected result (with/without a cancer diagnosis), were interviewed 6-months after their result. Participants described their experiences of diagnostic investigation within the NHS. Reflexive Thematic Analysis was used.
Findings: The journey through the period of diagnostic investigation was extremely varied since this was dependent on the predicted cancer site(s). Participant narratives demonstrated wide variation in the required tests, number of contacts with healthcare staff and duration of the whole process. Five themes were interpreted from participants' narratives: i) Feeling prepared for procedures; ii) Needing to advocate; iii) Needing to self-navigate: iv) Speed of the diagnostic process and having to wait; v) Reaching 'the end' of diagnostic work-up.
Interpretation: If MCED screening is implemented in future, it will be important to carefully consider implementation of appropriate diagnostic investigation for patients who have a cancer signal detected. We recommend minimising the length of the diagnostic testing period, offering patient navigation and formulating clear plans for what happens at the end of the patient journey. While our findings highlight important considerations to support positive experiences for those having follow-up tests after a cancer signal detected result, they also have broader application for improvement of cancer diagnostic pathways more generally.
Funding: This work was funded and sponsored by GRAIL Bio UK, Ltd. as a sub-study within the NHS-Galleri trial. GRAIL funded the costs of the data collection as well as staff salaries through a contract with King's College London/Queen Mary University of London.
背景:了解任何新的筛查方式的诊断调查经验对未来实施途径的发展至关重要。在NHS- galleri试验(NCT05611632)中,我们探索了在NHS内对血液多癌早期检测(MCED)筛查试验中检测到癌症信号的患者进行诊断检查的经验。方法:41名有癌症信号检测结果的参与者(有/没有癌症诊断),在结果6个月后接受采访。参与者描述了他们在NHS内诊断调查的经历。采用反身性主位分析。发现:诊断调查期间的旅程非常不同,因为这取决于预测的癌症部位。参与者的叙述表明,在所需的测试、与医护人员接触的次数和整个过程的持续时间方面存在很大差异。从参与者的叙述中解读了五个主题:i)对程序的准备;ii)需要倡导;iii)需要自我导航;iv)诊断过程速度快,需要等待;v)达到诊断检查的“终点”。解释:如果将来实施MCED筛查,对于检测到癌症信号的患者,仔细考虑实施适当的诊断调查将是重要的。我们建议尽量缩短诊断测试周期,为患者提供导航,并为患者旅程结束时的情况制定明确的计划。虽然我们的研究结果强调了一些重要的考虑因素,以支持那些在癌症信号检测结果后进行后续测试的人的积极体验,但它们在更广泛地改善癌症诊断途径方面也有更广泛的应用。经费:本研究由GRAIL Bio UK, Ltd.资助,作为NHS-Galleri试验的一个子研究。GRAIL通过与伦敦国王学院/伦敦玛丽女王大学签订的合同,资助了数据收集的费用以及工作人员的工资。
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Pub Date : 2026-01-08eCollection Date: 2026-01-01DOI: 10.1016/j.eclinm.2025.103750
Heinz Ludwig, Efstathios Kastritis, Sarah Bernhard, Niels W C J van de Donk, Mario Boccadoro, Evangelos Terpos, Pellegrino Musto, Pieter Sonneveld, Ghulam Rehman Mohyuddin
Background: Diagnostic advancements and classification updates appear to have reshaped the natural history of smoldering multiple myeloma (SMM), though this evolution has not been empirically quantified. We conducted a systematic review to evaluate temporal changes in SMM prognosis.
Methods: PubMed, EMBASE and the Cochrane library databases were searched from January 1990 to November 2025, yielding 1415 reports, of which 14 studies met inclusion criteria. To reconstruct individual-level data, published time to progression (TTP) curves were digitized using a Shiny web application. Kaplan-Meier (KM) survival curves and meta-analyses were generated in RStudio. PROSPERO ID 1068697.
Findings: Progression risk at two and ten years for all-risk patients was 22.8% and 60.1%, respectively; these increased to 44.7% and 85.6% in high-risk patients. Landmark analysis from year five revealed attenuated progression rates: 14.2% and 30.8% for all-risk, and 22.5% and 50.6% for high-risk patients at two and five years post-landmark, respectively. Studies enrolling most patients before 2014 showed higher progression rates than in more recent cohorts (Spearman's rho = 0.645, p = 0.034), but this trend did not reach statistical significance in high-risk groups (rho = 0.360, p = 0.272). Meta-analytic data further supported elevated progression in older cohorts.
Interpretation: SMM appears to follow a more indolent trajectory in recent years, likely due to improved diagnostic precision and exclusion of biomarker-defined or subclinical MM. Enhanced predictive models may better guide therapeutic decision-making, targeting treatment to those most likely to benefit and avoiding the burden of unnecessary intervention in low-risk individuals.
Funding: Supported by the Austrian Forum Against Cancer.
背景:诊断的进步和分类的更新似乎已经重塑了阴燃多发性骨髓瘤(SMM)的自然历史,尽管这种演变尚未被经验量化。我们进行了一项系统综述来评估颞叶变化对SMM预后的影响。方法:检索1990年1月至2025年11月PubMed、EMBASE和Cochrane图书馆数据库,共获得1415篇报道,其中14篇研究符合纳入标准。为了重建个人层面的数据,使用Shiny的web应用程序将发布的进度时间(TTP)曲线数字化。在RStudio中生成Kaplan-Meier (KM)生存曲线和meta分析。普洛斯彼罗id 1068697。结果:全危患者2年和10年的进展风险分别为22.8%和60.1%;在高危患者中,这一比例分别增加到44.7%和85.6%。从第5年开始的里程碑分析显示,在里程碑后2年和5年,全风险患者的进展率分别为14.2%和30.8%,高风险患者的进展率分别为22.5%和50.6%。在2014年之前纳入大多数患者的研究中,进展率高于最近的队列(Spearman’s rho = 0.645, p = 0.034),但这一趋势在高危组中没有统计学意义(rho = 0.360, p = 0.272)。荟萃分析数据进一步支持老年队列的进展加快。解释:近年来,SMM似乎遵循更惰性的轨迹,可能是由于提高了诊断精度和排除生物标志物定义或亚临床MM。增强的预测模型可以更好地指导治疗决策,针对那些最有可能受益的治疗,避免对低风险个体进行不必要干预的负担。资助:由奥地利抗癌论坛支持。
{"title":"Temporal trends in progression risk in smoldering myeloma: a systematic review.","authors":"Heinz Ludwig, Efstathios Kastritis, Sarah Bernhard, Niels W C J van de Donk, Mario Boccadoro, Evangelos Terpos, Pellegrino Musto, Pieter Sonneveld, Ghulam Rehman Mohyuddin","doi":"10.1016/j.eclinm.2025.103750","DOIUrl":"10.1016/j.eclinm.2025.103750","url":null,"abstract":"<p><strong>Background: </strong>Diagnostic advancements and classification updates appear to have reshaped the natural history of smoldering multiple myeloma (SMM), though this evolution has not been empirically quantified. We conducted a systematic review to evaluate temporal changes in SMM prognosis.</p><p><strong>Methods: </strong>PubMed, EMBASE and the Cochrane library databases were searched from January 1990 to November 2025, yielding 1415 reports, of which 14 studies met inclusion criteria. To reconstruct individual-level data, published time to progression (TTP) curves were digitized using a Shiny web application. Kaplan-Meier (KM) survival curves and meta-analyses were generated in RStudio. PROSPERO ID 1068697.</p><p><strong>Findings: </strong>Progression risk at two and ten years for all-risk patients was 22.8% and 60.1%, respectively; these increased to 44.7% and 85.6% in high-risk patients. Landmark analysis from year five revealed attenuated progression rates: 14.2% and 30.8% for all-risk, and 22.5% and 50.6% for high-risk patients at two and five years post-landmark, respectively. Studies enrolling most patients before 2014 showed higher progression rates than in more recent cohorts (Spearman's rho = 0.645, p = 0.034), but this trend did not reach statistical significance in high-risk groups (rho = 0.360, p = 0.272). Meta-analytic data further supported elevated progression in older cohorts.</p><p><strong>Interpretation: </strong>SMM appears to follow a more indolent trajectory in recent years, likely due to improved diagnostic precision and exclusion of biomarker-defined or subclinical MM. Enhanced predictive models may better guide therapeutic decision-making, targeting treatment to those most likely to benefit and avoiding the burden of unnecessary intervention in low-risk individuals.</p><p><strong>Funding: </strong>Supported by the Austrian Forum Against Cancer.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"91 ","pages":"103750"},"PeriodicalIF":10.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017908","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}
Pub Date : 2026-01-08eCollection Date: 2026-01-01DOI: 10.1016/j.eclinm.2025.103751
Victoria Bradley, Livia Samara, Miriam Toolan, Amelia Atkinson, Deborah M Caldwell, Abigail Fraser, Shakila Thangaratinam, Gemma Clayton, Abi Merriel
Background: Globally, around 2 million pregnancies each year end in stillbirth, with the majority occurring in low and middle-income countries. The association between gestational diabetes mellitus (GDM) and stillbirth has been widely researched but the evidence is increasingly controversial. The aim of this study is to evaluate the risk of stillbirth associated with GDM, and examine whether this risk differs according to country income status and GDM screening method.
Methods: We searched Scopus, Cinahl, Cochrane Central, ISRCTN, Medline, Embase and Epistemonikos on the 9th May 2025 from inception to May 2025 with no restrictions based on language, study location or time. We included cohort studies that estimated the association of interest. We conducted a random effects meta-analysis by study design and sub-group analyses by country income level and GDM screening method. (PROSPERO CRD4201800057).
Findings: 101 included studies (92,915,856 women) presented unadjusted results, 19 reported adjusted results (63,629,536 women). Meta-analysis of adjusted cohort data did not show evidence of an association between a diagnosis of GDM and the risk of stillbirth worldwide (OR 0.81, 95% CI: 0.68-0.97; I2 = 87.7%; n = 19 studies). However, when stratified by country income level a diagnosis of GDM was associated with a reduction in the odds of stillbirth in high income countries (OR 0.73, 95% CI: 0.65-0.82; I2 = 31.9%; n = 13 studies), but this was not observed in upper and lower middle income countries, (OR 1.17, 95% CI: 0.71-1.93; I2 = 59.7%; n = 6 studies). There were no adjusted estimates from low-income countries. There was no evidence of a difference by GDM screening method.
Interpretation: Increased screening, timely diagnosis and effective management strategies for GDM in high-income countries, such as induction of labour and increased antenatal care, may be responsible for the reduced risk of stillbirth in women with GDM. Further research is needed to identify the optimum strategy for screening and management in low and middle-income settings to reduce preventable stillbirths worldwide.
{"title":"Gestational diabetes and stillbirth: a systematic review and meta-analysis.","authors":"Victoria Bradley, Livia Samara, Miriam Toolan, Amelia Atkinson, Deborah M Caldwell, Abigail Fraser, Shakila Thangaratinam, Gemma Clayton, Abi Merriel","doi":"10.1016/j.eclinm.2025.103751","DOIUrl":"10.1016/j.eclinm.2025.103751","url":null,"abstract":"<p><strong>Background: </strong>Globally, around 2 million pregnancies each year end in stillbirth, with the majority occurring in low and middle-income countries. The association between gestational diabetes mellitus (GDM) and stillbirth has been widely researched but the evidence is increasingly controversial. The aim of this study is to evaluate the risk of stillbirth associated with GDM, and examine whether this risk differs according to country income status and GDM screening method.</p><p><strong>Methods: </strong>We searched Scopus, Cinahl, Cochrane Central, ISRCTN, Medline, Embase and Epistemonikos on the 9th May 2025 from inception to May 2025 with no restrictions based on language, study location or time. We included cohort studies that estimated the association of interest. We conducted a random effects meta-analysis by study design and sub-group analyses by country income level and GDM screening method. (PROSPERO CRD4201800057).</p><p><strong>Findings: </strong>101 included studies (92,915,856 women) presented unadjusted results, 19 reported adjusted results (63,629,536 women). Meta-analysis of adjusted cohort data did not show evidence of an association between a diagnosis of GDM and the risk of stillbirth worldwide (OR 0.81, 95% CI: 0.68-0.97; I<sup>2</sup> = 87.7%; n = 19 studies). However, when stratified by country income level a diagnosis of GDM was associated with a reduction in the odds of stillbirth in high income countries (OR 0.73, 95% CI: 0.65-0.82; I<sup>2</sup> = 31.9%; n = 13 studies), but this was not observed in upper and lower middle income countries, (OR 1.17, 95% CI: 0.71-1.93; I<sup>2</sup> = 59.7%; n = 6 studies). There were no adjusted estimates from low-income countries. There was no evidence of a difference by GDM screening method.</p><p><strong>Interpretation: </strong>Increased screening, timely diagnosis and effective management strategies for GDM in high-income countries, such as induction of labour and increased antenatal care, may be responsible for the reduced risk of stillbirth in women with GDM. Further research is needed to identify the optimum strategy for screening and management in low and middle-income settings to reduce preventable stillbirths worldwide.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"91 ","pages":"103751"},"PeriodicalIF":10.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017918","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}
Pub Date : 2026-01-08eCollection Date: 2026-01-01DOI: 10.1016/j.eclinm.2025.103742
Zeynep Elmas, Christine Herrmann, Kathrin Kramer, Oender Soylu, Vanessa Roemer, Luisa Jagodzinski, Lars Richter, Maximilian Wiesenfarth, Tanja Fangerau, Stefanie Jung, Regina Gastl, Angela Rosenbohm, Jochen H Weishaupt, Makbule Senel, Benjamin Mayer, Hayrettin Tumani, Johannes Dorst
<p><strong>Background: </strong>Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune-inflammatory disease of the peripheral nervous system. Corticosteroids, intravenous immunoglobulins (IVIGs), and plasma exchange (PLEX) constitute the main therapeutic options, but immunoadsorption (IA) represents a noteworthy alternative to PLEX due to its excellent tolerability and its capability to remove higher rates of autoimmune antibodies. However, evidence of its therapeutic value in CIDP is low, while the effect of repeated IA as long-term therapy is largely unknown. Therefore, in this study, we sought to evaluate the short- and long-term therapeutic effects of IA in CIDP compared to PLEX and preceding therapies (IVIGs and corticosteroids).</p><p><strong>Methods: </strong>Between 02/12/2013 and 03/03/2025, we prospectively evaluated the course of disease of patients with CIDP who received at least one cycle of IA or PLEX via Shaldon catheter or arteriovenous shunt. All patients were treated in the Department of Neurology of Ulm University, Germany. All patients fulfilled the diagnostic criteria of typical CIDP according to the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline on diagnosis and treatment of CIDP, had a continuously progressive course of disease, and had previously received treatment with steroids, IVIGs, or both, with insufficient response. All eligible patients who gave their informed consent were selected for the study. Participant data were collected and retrieved using individual case report forms and medical records. One cycle of IA or PLEX consisted of 5 treatments on 5 consecutive days. As the primary outcome parameter, we used a combined CIDP score of 3 validated scales comprising disability (Inflammatory Neuropathy Cause and Treatment (INCAT) score), motor score (Medical Research Council, MRC), and vibration sensitivity (tuning fork test). For short-term effects, we compared absolute CIDP scores 3 days before and directly after the last treatment of each cycle; for long-term effects, we compared changes of CIDP score per month during IA or PLEX compared to preceding treatments in patients with an observation period of at least 6 continuous months under IA or PLEX. We systematically evaluated adverse events (AEs), and collected safety laboratory data as well as immunoglobulin (Ig) reduction levels.</p><p><strong>Findings: </strong>In total, 80 patients were included, of which 74 received at least one cycle of IA, 25 received at least one cycle of PLEX, and 19 received at least one cycle of both IA and PLEX and were considered for both treatment groups for respective analyses. 41 IA patients and 16 PLEX patients received 2 or more cycles (median 4 (IQR 2-7.5), maximum 43 cycles) over a median time period of 12.0 (6.0-34.0) months in median time intervals of 2.5 (1.9-4.3) months. We observed improvements of CIDP scores post-treatment in the IA group (median improvement from 310 (224-374)
背景:慢性炎症性脱髓鞘性多神经病变(CIDP)是一种周围神经系统的自身免疫性炎症性疾病。皮质类固醇、静脉注射免疫球蛋白(IVIGs)和血浆置换(PLEX)是主要的治疗选择,但免疫吸附(IA)由于其优异的耐受性和去除更高自身免疫抗体率的能力,是值得注意的PLEX替代方案。然而,它在CIDP中的治疗价值的证据很少,而重复IA作为长期治疗的效果在很大程度上是未知的。因此,在本研究中,我们试图评估IA在CIDP中的短期和长期治疗效果,与PLEX和之前的治疗方法(ivig和皮质类固醇)相比。方法:2013年12月2日至2025年3月3日期间,通过Shaldon导管或动静脉分流术接受至少一个周期IA或PLEX治疗的CIDP患者的病程进行前瞻性评估。所有患者均在德国乌尔姆大学神经内科接受治疗。所有患者均符合欧洲神经病学学会/周围神经学会(EAN/PNS) CIDP诊断和治疗指南的典型CIDP诊断标准,病程持续进展,既往曾接受类固醇、ivig或两者治疗,但反应不足。所有给予知情同意的符合条件的患者都被选中参加这项研究。使用个案报告表格和医疗记录收集和检索参与者数据。一个周期为连续5天5次治疗。作为主要结局参数,我们使用了由3个有效量表组成的综合CIDP评分,包括残疾(炎症性神经病变病因和治疗(INCAT)评分)、运动评分(医学研究委员会,MRC)和振动敏感性(音叉测试)。对于短期疗效,我们比较每个周期末次治疗前后3天的绝对CIDP评分;对于长期效果,我们比较了在IA或PLEX下观察期至少连续6个月的患者在IA或PLEX下每月CIDP评分与治疗前的变化。我们系统地评估了不良事件(ae),并收集了安全实验室数据以及免疫球蛋白(Ig)降低水平。结果:共纳入80例患者,其中74例接受了至少一个周期的IA, 25例接受了至少一个周期的PLEX, 19例同时接受了至少一个周期的IA和PLEX,并被考虑为两个治疗组进行各自的分析。41例IA患者和16例PLEX患者接受了2个或2个以上周期(中位4 (IQR 2-7.5),最大43个周期),中位时间间隔为2.5(1.9-4.3)个月,中位时间为12.0(6.0-34.0)个月。我们观察到IA组治疗后CIDP评分的改善(中位改善从310(224-374)到321(234-373)分;中位差为5.0 (95% CI 2.0-6.0), p < 0.0001),但PLEX组中位差为254(214-358)比254 (209-351);中位差为0.0 (95% CI为0.0-5.0,p = 0.12)。与之前的皮质类固醇和IVIG治疗相比,IA组的长期进展率从3.8(2.2-9.1)降至0.2(-0.5-2.2)点/月(中位数差值-4.0 (95% CI -6.9至-1.9),p < 0.0001), PLEX组从4.2(2.6-17.2)降至-1.1(-1.6-0.5)点/月(中位数差值-6.3 (95% CI -19.9至-1.9),p = 0.0010),对应于疾病进展的临床稳定。我们在240个IA周期中检测到12例(5.0%)无症状和3例(1.3%)有症状的颈静脉血栓形成,在PLEX组的79个周期中检测到6例(7.5%)颈静脉血栓形成(均无症状),这代表了两种手术的主要并发症。在两组中,低蛋白血症(IA 100%, PLEX 93.5%)、血小板减少症(IA 33.6%, PLEX 4.9%)和贫血(IA 21.6%, PLEX 61.8%)是治疗期间最常见的实验室发现。解释:我们的研究结果表明,对于对皮质类固醇和ivig没有充分反应的CIDP患者,重复IA和PLEX可能是有希望的治疗选择,可以稳定大多数患者的疾病。然而,它的侵入性和颈静脉血栓形成的重大风险必须考虑。研究的局限性包括非随机分组、既往治疗相关数据的回顾性收集、基线前治疗次优的可能性、有限的患者数量以及由于观察时间长导致的潜在干扰因素(如IA和PLEX之间的交叉)。由于这些局限性,研究结果不允许直接比较IA和PLEX之间的有效性,在这方面需要进一步的随机对照试验。资助:这是一项由研究者发起的研究,没有机构或行业资助。
{"title":"Evaluating the short-term and long-term therapeutic effects of immunoadsorption compared with plasma exchange in chronic inflammatory demyelinating polyneuropathy: a long-term, prospective, observational study.","authors":"Zeynep Elmas, Christine Herrmann, Kathrin Kramer, Oender Soylu, Vanessa Roemer, Luisa Jagodzinski, Lars Richter, Maximilian Wiesenfarth, Tanja Fangerau, Stefanie Jung, Regina Gastl, Angela Rosenbohm, Jochen H Weishaupt, Makbule Senel, Benjamin Mayer, Hayrettin Tumani, Johannes Dorst","doi":"10.1016/j.eclinm.2025.103742","DOIUrl":"10.1016/j.eclinm.2025.103742","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune-inflammatory disease of the peripheral nervous system. Corticosteroids, intravenous immunoglobulins (IVIGs), and plasma exchange (PLEX) constitute the main therapeutic options, but immunoadsorption (IA) represents a noteworthy alternative to PLEX due to its excellent tolerability and its capability to remove higher rates of autoimmune antibodies. However, evidence of its therapeutic value in CIDP is low, while the effect of repeated IA as long-term therapy is largely unknown. Therefore, in this study, we sought to evaluate the short- and long-term therapeutic effects of IA in CIDP compared to PLEX and preceding therapies (IVIGs and corticosteroids).</p><p><strong>Methods: </strong>Between 02/12/2013 and 03/03/2025, we prospectively evaluated the course of disease of patients with CIDP who received at least one cycle of IA or PLEX via Shaldon catheter or arteriovenous shunt. All patients were treated in the Department of Neurology of Ulm University, Germany. All patients fulfilled the diagnostic criteria of typical CIDP according to the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline on diagnosis and treatment of CIDP, had a continuously progressive course of disease, and had previously received treatment with steroids, IVIGs, or both, with insufficient response. All eligible patients who gave their informed consent were selected for the study. Participant data were collected and retrieved using individual case report forms and medical records. One cycle of IA or PLEX consisted of 5 treatments on 5 consecutive days. As the primary outcome parameter, we used a combined CIDP score of 3 validated scales comprising disability (Inflammatory Neuropathy Cause and Treatment (INCAT) score), motor score (Medical Research Council, MRC), and vibration sensitivity (tuning fork test). For short-term effects, we compared absolute CIDP scores 3 days before and directly after the last treatment of each cycle; for long-term effects, we compared changes of CIDP score per month during IA or PLEX compared to preceding treatments in patients with an observation period of at least 6 continuous months under IA or PLEX. We systematically evaluated adverse events (AEs), and collected safety laboratory data as well as immunoglobulin (Ig) reduction levels.</p><p><strong>Findings: </strong>In total, 80 patients were included, of which 74 received at least one cycle of IA, 25 received at least one cycle of PLEX, and 19 received at least one cycle of both IA and PLEX and were considered for both treatment groups for respective analyses. 41 IA patients and 16 PLEX patients received 2 or more cycles (median 4 (IQR 2-7.5), maximum 43 cycles) over a median time period of 12.0 (6.0-34.0) months in median time intervals of 2.5 (1.9-4.3) months. We observed improvements of CIDP scores post-treatment in the IA group (median improvement from 310 (224-374) ","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"91 ","pages":"103742"},"PeriodicalIF":10.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017940","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}
Pub Date : 2026-01-07eCollection Date: 2026-01-01DOI: 10.1016/j.eclinm.2025.103748
Andrea Amerio, Enrico Venturini, Mirko Capanna, Luca Ploner, Irene Schiavetti, Alessandra Costanza, Massimiliano Clausi, Paola Bertuccio, Anna Odone, Helen Minnis, Ruchika Gajwani, Renato de Filippis, Pasquale De Fazio, Mario Amore, Andrea Aguglia, Gianluca Serafini
Background: Suicide rates have risen among young people, making it a leading cause of adolescent death worldwide. Although several pharmacological treatments have been approved in the context of definite underlying conditions, their broader efficacy in reducing suicidality remains unclear.
Methods: A structured review was conducted on pharmacological treatments for suicidality in under 18s. PubMed, Embase, PsycINFO, and Cochrane Library were searched from inception to 31 July 2025. Eligible studies included patients <18 years with suicidality treated with antidepressants, mood stabilisers, or antipsychotics. Exclusion criteria were non-pharmacological interventions, non-suicidal self-injury-only studies, reviews, and grey literature. Both interventional and observational designs were considered. Four authors independently screened, extracted, and appraised data using Joanna Briggs Institute tools. The primary outcome was suicidality reduction, synthesised narratively. This study is registered with PROSPERO, CRD42024548628.
Findings: Twenty-three articles out of 1747 met inclusion criteria, totalling 2235 participants. Risk of bias across studies was low-to-moderate for nearly all studies (22/23). However, the majority employed weaker study designs and targeted underlying diagnoses, with suicidality rarely assessed as a primary outcome. Esketamine (four studies, n = 211) and ketamine (four, n = 6) use in major depressive disorder induced rapid reduction of acute suicidality within 24 h. In the longer term, lithium (three, n = 923) was beneficial in reducing suicidality in youths with bipolar disorder. Sertraline, citalopram, escitalopram, fluoxetine and duloxetine (six, n = 906) yielded inconsistent results. Other agents, including valproate, lamotrigine and antipsychotics such as clozapine and quetiapine exhibited some benefit in reducing suicidality, but findings were limited to small-scale studies.
Interpretation: Evidence remains scarce and heterogeneous. Esketamine and lithium appear promising for acute and chronic suicidality, respectively. Further high-quality studies investigating suicidal thoughts and behaviours as independent treatment targets are needed to guide clinical decision-making.
{"title":"Exploring the effects of pharmacological treatments on suicidality in children and adolescents: a structured review of the literature and narrative synthesis.","authors":"Andrea Amerio, Enrico Venturini, Mirko Capanna, Luca Ploner, Irene Schiavetti, Alessandra Costanza, Massimiliano Clausi, Paola Bertuccio, Anna Odone, Helen Minnis, Ruchika Gajwani, Renato de Filippis, Pasquale De Fazio, Mario Amore, Andrea Aguglia, Gianluca Serafini","doi":"10.1016/j.eclinm.2025.103748","DOIUrl":"10.1016/j.eclinm.2025.103748","url":null,"abstract":"<p><strong>Background: </strong>Suicide rates have risen among young people, making it a leading cause of adolescent death worldwide. Although several pharmacological treatments have been approved in the context of definite underlying conditions, their broader efficacy in reducing suicidality remains unclear.</p><p><strong>Methods: </strong>A structured review was conducted on pharmacological treatments for suicidality in under 18s. PubMed, Embase, PsycINFO, and Cochrane Library were searched from inception to 31 July 2025. Eligible studies included patients <18 years with suicidality treated with antidepressants, mood stabilisers, or antipsychotics. Exclusion criteria were non-pharmacological interventions, non-suicidal self-injury-only studies, reviews, and grey literature. Both interventional and observational designs were considered. Four authors independently screened, extracted, and appraised data using Joanna Briggs Institute tools. The primary outcome was suicidality reduction, synthesised narratively. This study is registered with PROSPERO, CRD42024548628.</p><p><strong>Findings: </strong>Twenty-three articles out of 1747 met inclusion criteria, totalling 2235 participants. Risk of bias across studies was low-to-moderate for nearly all studies (22/23). However, the majority employed weaker study designs and targeted underlying diagnoses, with suicidality rarely assessed as a primary outcome. Esketamine (four studies, <i>n</i> = 211) and ketamine (four, <i>n</i> = 6) use in major depressive disorder induced rapid reduction of acute suicidality within 24 h. In the longer term, lithium (three, <i>n</i> = 923) was beneficial in reducing suicidality in youths with bipolar disorder. Sertraline, citalopram, escitalopram, fluoxetine and duloxetine (six, <i>n</i> = 906) yielded inconsistent results. Other agents, including valproate, lamotrigine and antipsychotics such as clozapine and quetiapine exhibited some benefit in reducing suicidality, but findings were limited to small-scale studies.</p><p><strong>Interpretation: </strong>Evidence remains scarce and heterogeneous. Esketamine and lithium appear promising for acute and chronic suicidality, respectively. Further high-quality studies investigating suicidal thoughts and behaviours as independent treatment targets are needed to guide clinical decision-making.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"91 ","pages":"103748"},"PeriodicalIF":10.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12814428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009120","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}
Pub Date : 2026-01-06eCollection Date: 2026-01-01DOI: 10.1016/j.eclinm.2025.103734
Felicity Evison, Suzy Gallier, Fatima Malik, Charlotte Stephens, Charles J Ferro, Jonathan Townend, William Moody, Matthew J Armstrong, Adnan Sharif
Background: Major adverse cardiovascular events (MACE) are common early after liver transplantation (LT) as reported in the United States, but incidence is not well described in a European cohort. With lower MACE rates reported after kidney transplantation in the United Kingdom versus the United States, it is important to determine if a similar incongruity exists after LT.
Methods: In this large retrospective, population cohort study, we studied all LT procedures performed in England between 1st April 2002 and 31st March 2023 (n = 10,213). MACE data was obtained from Hospital Episode Statistics, an administration data warehouse for any hospitalization to English NHS hospital, and defined as any of the following: myocardial infarction, stroke, unstable angina, heart failure, any coronary revascularization procedure and any cardiovascular-defined death.
Findings: MACE-related 1-year mortality was low at 0.1% (n = 11). Overall, MACE occurred in 268 (2.6%) LT recipients within the first year after LT, of which 125 (1.2%) occurred within the first month. The commonest observed MACE was stroke (n = 129, 1.3%), followed by myocardial infarction (n = 89, 0.9%). After adjustment, MACE within the first year was associated with increased risk for long-term all-cause mortality (Hazard Ratio 1.37, 95% CI 1.05-1.79, p = 0.021). In a competing risk regression model, with non-cardiac death a competing risk, the following were independently associated with increased risk of MACE after LT: increasing age, male sex, diabetes, and higher Charlson co-morbidity score.
Interpretation: MACE and cardiovascular death are uncommon within the first-year post LT in England. However, liver transplant recipients with non-fatal MACE have inferior long-term survival. Further work is warranted to determine the best strategy to mitigate cardiac risk stratification for LT candidates and evidence-based strategies to mitigate cardiovascular risk after LT must be encouraged.
Funding: Nothing to disclose.
背景:据美国报道,主要不良心血管事件(MACE)在肝移植(LT)后早期很常见,但在欧洲队列中发病率并未得到很好的描述。与美国相比,英国肾移植术后MACE发生率较低,因此确定肝移植后是否存在类似的不一致性是很重要的。方法:在这项大型回顾性人群队列研究中,我们研究了2002年4月1日至2023年3月31日在英国进行的所有肝移植手术(n = 10,213)。MACE数据来自医院事件统计(Hospital Episode Statistics),这是英国NHS医院住院的管理数据仓库,定义为以下任何一种:心肌梗死、中风、不稳定型心绞痛、心力衰竭、任何冠状动脉血运重建术和任何心血管疾病定义的死亡。结果:mace相关的1年死亡率较低,为0.1% (n = 11)。总体而言,268例(2.6%)肝移植受者在肝移植后的第一年内发生MACE,其中125例(1.2%)发生在第一个月内。最常见的MACE是脑卒中(n = 129, 1.3%),其次是心肌梗死(n = 89, 0.9%)。调整后,第一年的MACE与长期全因死亡风险增加相关(风险比1.37,95% CI 1.05-1.79, p = 0.021)。在竞争风险回归模型中,非心源性死亡是竞争风险,以下因素与肝移植后MACE风险增加独立相关:年龄增加、男性、糖尿病和较高的Charlson合并症评分。解释:在英格兰,MACE和心血管死亡在肝移植后一年内并不常见。然而,非致死性MACE肝移植受者的长期生存率较低。需要进一步的工作来确定减轻肝移植候选人心脏风险分层的最佳策略,并且必须鼓励采取循证策略来减轻肝移植后心血管风险。资金来源:无需透露。
{"title":"Major adverse cardiovascular events after liver transplantation: a population cohort analysis of English transplant centres.","authors":"Felicity Evison, Suzy Gallier, Fatima Malik, Charlotte Stephens, Charles J Ferro, Jonathan Townend, William Moody, Matthew J Armstrong, Adnan Sharif","doi":"10.1016/j.eclinm.2025.103734","DOIUrl":"10.1016/j.eclinm.2025.103734","url":null,"abstract":"<p><strong>Background: </strong>Major adverse cardiovascular events (MACE) are common early after liver transplantation (LT) as reported in the United States, but incidence is not well described in a European cohort. With lower MACE rates reported after kidney transplantation in the United Kingdom versus the United States, it is important to determine if a similar incongruity exists after LT.</p><p><strong>Methods: </strong>In this large retrospective, population cohort study, we studied all LT procedures performed in England between 1st April 2002 and 31st March 2023 (n = 10,213). MACE data was obtained from Hospital Episode Statistics, an administration data warehouse for any hospitalization to English NHS hospital, and defined as any of the following: myocardial infarction, stroke, unstable angina, heart failure, any coronary revascularization procedure and any cardiovascular-defined death.</p><p><strong>Findings: </strong>MACE-related 1-year mortality was low at 0.1% (n = 11). Overall, MACE occurred in 268 (2.6%) LT recipients within the first year after LT, of which 125 (1.2%) occurred within the first month. The commonest observed MACE was stroke (n = 129, 1.3%), followed by myocardial infarction (n = 89, 0.9%). After adjustment, MACE within the first year was associated with increased risk for long-term all-cause mortality (Hazard Ratio 1.37, 95% CI 1.05-1.79, p = 0.021). In a competing risk regression model, with non-cardiac death a competing risk, the following were independently associated with increased risk of MACE after LT: increasing age, male sex, diabetes, and higher Charlson co-morbidity score.</p><p><strong>Interpretation: </strong>MACE and cardiovascular death are uncommon within the first-year post LT in England. However, liver transplant recipients with non-fatal MACE have inferior long-term survival. Further work is warranted to determine the best strategy to mitigate cardiac risk stratification for LT candidates and evidence-based strategies to mitigate cardiovascular risk after LT must be encouraged.</p><p><strong>Funding: </strong>Nothing to disclose.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"91 ","pages":"103734"},"PeriodicalIF":10.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997164","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}
Pub Date : 2026-01-05eCollection Date: 2026-01-01DOI: 10.1016/j.eclinm.2025.103708
Feifei Li, Yusha Tao, Chengxin Fan, Yifan Dai, Jamie L Conklin, Joseph D Tucker, Roger Chou, Philippa Easterbrook, Weiming Tang
<p><strong>Background: </strong>Chronic hepatitis D (CHD) coinfection leads to accelerated progression to liver cirrhosis, hepatocellular carcinoma, and increased mortality. Currently, only a small proportion of individuals who are HBsAg positive are tested for anti-HDV antibodies, and among those who test positive, few receive confirmatory HDV RNA testing. Reflex testing, whereby laboratory-based anti-HDV testing is automatically triggered with a positive HBsAg test result in the lab, and also HDV RNA testing in those with a positive anti-HDV result, is one approach to promote the uptake and earlier diagnosis of HDV coinfection. We undertook a systematic review and meta-analysis to evaluate the effectiveness of a laboratory-based reflex testing strategy for both anti-HDV and HDV RNA on uptake of testing and linkage to care and turnaround times across the care cascade.</p><p><strong>Methods: </strong>We searched five databases (PubMed, Scopus, Embase, Cochrane, and Global Health (EBSCOhost)) and conference abstracts for relevant studies from database inception through June 2025, with or without a non-reflex comparator arm, and that had data on at least one step in the care cascade (uptake of HDV antibody and HDV RNA testing, linkage to care, and treatment initiation). Summary estimates were calculated using random-effects meta-analyses with 95% confidence intervals (CIs). The strength of evidence was assessed using the GRADE framework. The protocol was registered with PROSPERO (CRD42023397577).</p><p><strong>Findings: </strong>Of 3160 studies identified in the search, 28 were eligible for inclusion, of which 9 also had a non-reflex comparison arm. The majority (82.1%) were conducted in high-income countries. Among the 28 studies that used a reflex testing, 97.1% (95% CI: 93.9-98.7) of HBsAg-positive individuals had anti-HDV testing, and 7.2% (95% CI: 5.8-8.9) were anti-HDV positive. Of these, 95.3% (95% CI: 90.1-97.8) had HDV RNA testing, and 43.2% (95% CI: 33.2-53.8) were RNA positive. In the nine studies with a non-reflex comparison arm, reflex testing significantly increased anti-HDV testing uptake (98.0% versus 39.7%; RR 2.55, 95% CI: 1.62-4.05). And in the six studies with a comparator arm that also examined HDV RNA testing, uptake was higher with reflex testing but this was not statistically significant (94.7% versus 79.9%; RR 1.02, 95% CI: 0.86-1.20). Nine studies reported turnaround times for reflex testing from HBsAg testing to anti-HDV reflex testing, and all were completed within the same day. Four studies also reported a same-day turnaround for HDV RNA testing. Linkage to care was reported in only three of the reflex testing studies, and all 6 HDV RNA-positive individuals were referred for care.</p><p><strong>Interpretation: </strong>Laboratory-based reflex testing significantly increased the uptake of anti-HDV antibody and HDV RNA testing across diverse populations and settings, with same day turnaround times. The 2024 World Health O
{"title":"Double reflex testing for anti-HDV antibody following an HBsAg-positive test result and HDV RNA in those anti-HDV positive: a global systematic review and meta-analysis.","authors":"Feifei Li, Yusha Tao, Chengxin Fan, Yifan Dai, Jamie L Conklin, Joseph D Tucker, Roger Chou, Philippa Easterbrook, Weiming Tang","doi":"10.1016/j.eclinm.2025.103708","DOIUrl":"10.1016/j.eclinm.2025.103708","url":null,"abstract":"<p><strong>Background: </strong>Chronic hepatitis D (CHD) coinfection leads to accelerated progression to liver cirrhosis, hepatocellular carcinoma, and increased mortality. Currently, only a small proportion of individuals who are HBsAg positive are tested for anti-HDV antibodies, and among those who test positive, few receive confirmatory HDV RNA testing. Reflex testing, whereby laboratory-based anti-HDV testing is automatically triggered with a positive HBsAg test result in the lab, and also HDV RNA testing in those with a positive anti-HDV result, is one approach to promote the uptake and earlier diagnosis of HDV coinfection. We undertook a systematic review and meta-analysis to evaluate the effectiveness of a laboratory-based reflex testing strategy for both anti-HDV and HDV RNA on uptake of testing and linkage to care and turnaround times across the care cascade.</p><p><strong>Methods: </strong>We searched five databases (PubMed, Scopus, Embase, Cochrane, and Global Health (EBSCOhost)) and conference abstracts for relevant studies from database inception through June 2025, with or without a non-reflex comparator arm, and that had data on at least one step in the care cascade (uptake of HDV antibody and HDV RNA testing, linkage to care, and treatment initiation). Summary estimates were calculated using random-effects meta-analyses with 95% confidence intervals (CIs). The strength of evidence was assessed using the GRADE framework. The protocol was registered with PROSPERO (CRD42023397577).</p><p><strong>Findings: </strong>Of 3160 studies identified in the search, 28 were eligible for inclusion, of which 9 also had a non-reflex comparison arm. The majority (82.1%) were conducted in high-income countries. Among the 28 studies that used a reflex testing, 97.1% (95% CI: 93.9-98.7) of HBsAg-positive individuals had anti-HDV testing, and 7.2% (95% CI: 5.8-8.9) were anti-HDV positive. Of these, 95.3% (95% CI: 90.1-97.8) had HDV RNA testing, and 43.2% (95% CI: 33.2-53.8) were RNA positive. In the nine studies with a non-reflex comparison arm, reflex testing significantly increased anti-HDV testing uptake (98.0% versus 39.7%; RR 2.55, 95% CI: 1.62-4.05). And in the six studies with a comparator arm that also examined HDV RNA testing, uptake was higher with reflex testing but this was not statistically significant (94.7% versus 79.9%; RR 1.02, 95% CI: 0.86-1.20). Nine studies reported turnaround times for reflex testing from HBsAg testing to anti-HDV reflex testing, and all were completed within the same day. Four studies also reported a same-day turnaround for HDV RNA testing. Linkage to care was reported in only three of the reflex testing studies, and all 6 HDV RNA-positive individuals were referred for care.</p><p><strong>Interpretation: </strong>Laboratory-based reflex testing significantly increased the uptake of anti-HDV antibody and HDV RNA testing across diverse populations and settings, with same day turnaround times. The 2024 World Health O","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"91 ","pages":"103708"},"PeriodicalIF":10.0,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997628","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}
Pub Date : 2026-01-05eCollection Date: 2026-01-01DOI: 10.1016/j.eclinm.2025.103740
Barbara Illowsky Karp, Hannah K Tandon, Ninet Sinaii, Jacqueline V Aredo, Vy T Phan, Noemi Salmeri, Jay P Shah, Melissa A Merideth, Pamela Stratton
Background: Chronic pelvic pain affects one in four women. Botulinum toxin, approved for chronic migraine and cervical dystonia pain, is an emerging treatment for other pain conditions. We evaluated intramuscular pelvic floor botulinum toxin injection in women with endometriosis-associated chronic pelvic pain and pelvic floor muscle spasm, hypothesising that botulinum toxin might reduce both spasm and pain.
Methods: In this a randomised, double-masked, parallel, phase 2 trial, women with pelvic floor spasm and pain despite standard endometriosis-specific and pain treatment were randomily assigned 1:1 to injection of 100 Units onabotulinumtoxinA (15 participants) or saline placebo (14 participants) into pelvic floor muscles. The primary outcome was patient report of benefit or no benefit assessed 1 month after masked injection. Patients could choose an open injection from 1 to 12 months after masked injection. Secondary outcomes (pain rating, pain medication usage, effect duration, and other participant-reported measures) were compared to baseline ratings. This study is registered with ClinicalTrials.gov, NCT01553201.
Findings: 29 participants were recruited between July 24, 2014 and May 8, 2018. All enrolled women completed the study. At 1 month, significantly more women in the toxin group reported benefit (11 (73%) of 15 vs 4 (29%) of 14; p = 0.027). Women receiving toxin attained a greater percent benefit (p = 0.034) and longer duration (p = 0.023) of pain relief. Those with at least moderate baseline pain had lower pain scores after toxin (p = 0.028). Benefit was present at 1 year in 16 of those requesting open injection (7 of 14 receiving placebo; 9 of 13 receiving toxin). 20 (77%) of 26 patients used less pain medication at 1-year (p < 0.0001), with 12 (92%) of 13 in the BoNT group and eight (62%) of 13 in the placebo group using less medication (p = 0.061). Adverse events were non-serious with no grade 3 or 4 adverse events or deaths, and were similar in both cohorts following masked and open injections.
Interpretation: This study demonstrates the efficacy and safety of pelvic floor botulinum toxin injection for women with endometriosis-associated chronic pelvic pain and pelvic floor spasm.
Funding: The study was supported by the Intramural Research Program of the U.S. National Institutes of Health (NIH). Allergan, Inc. provided study drug and independent monitoring funds under a Clinical Trial Agreement with NIH and had no other role in the study.
{"title":"Botulinum toxin for endometriosis-associated chronic pelvic pain: a randomised, double-masked, parallel, phase 2 trial.","authors":"Barbara Illowsky Karp, Hannah K Tandon, Ninet Sinaii, Jacqueline V Aredo, Vy T Phan, Noemi Salmeri, Jay P Shah, Melissa A Merideth, Pamela Stratton","doi":"10.1016/j.eclinm.2025.103740","DOIUrl":"10.1016/j.eclinm.2025.103740","url":null,"abstract":"<p><strong>Background: </strong>Chronic pelvic pain affects one in four women. Botulinum toxin, approved for chronic migraine and cervical dystonia pain, is an emerging treatment for other pain conditions. We evaluated intramuscular pelvic floor botulinum toxin injection in women with endometriosis-associated chronic pelvic pain and pelvic floor muscle spasm, hypothesising that botulinum toxin might reduce both spasm and pain.</p><p><strong>Methods: </strong>In this a randomised, double-masked, parallel, phase 2 trial, women with pelvic floor spasm and pain despite standard endometriosis-specific and pain treatment were randomily assigned 1:1 to injection of 100 Units onabotulinumtoxinA (15 participants) or saline placebo (14 participants) into pelvic floor muscles. The primary outcome was patient report of benefit or no benefit assessed 1 month after masked injection. Patients could choose an open injection from 1 to 12 months after masked injection. Secondary outcomes (pain rating, pain medication usage, effect duration, and other participant-reported measures) were compared to baseline ratings. This study is registered with ClinicalTrials.gov, NCT01553201.</p><p><strong>Findings: </strong>29 participants were recruited between July 24, 2014 and May 8, 2018. All enrolled women completed the study. At 1 month, significantly more women in the toxin group reported benefit (11 (73%) of 15 vs 4 (29%) of 14; p = 0.027). Women receiving toxin attained a greater percent benefit (p = 0.034) and longer duration (p = 0.023) of pain relief. Those with at least moderate baseline pain had lower pain scores after toxin (p = 0.028). Benefit was present at 1 year in 16 of those requesting open injection (7 of 14 receiving placebo; 9 of 13 receiving toxin). 20 (77%) of 26 patients used less pain medication at 1-year (p < 0.0001), with 12 (92%) of 13 in the BoNT group and eight (62%) of 13 in the placebo group using less medication (p = 0.061). Adverse events were non-serious with no grade 3 or 4 adverse events or deaths, and were similar in both cohorts following masked and open injections.</p><p><strong>Interpretation: </strong>This study demonstrates the efficacy and safety of pelvic floor botulinum toxin injection for women with endometriosis-associated chronic pelvic pain and pelvic floor spasm.</p><p><strong>Funding: </strong>The study was supported by the Intramural Research Program of the U.S. National Institutes of Health (NIH). Allergan, Inc. provided study drug and independent monitoring funds under a Clinical Trial Agreement with NIH and had no other role in the study.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"91 ","pages":"103740"},"PeriodicalIF":10.0,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997664","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}