EClinicalMedicine最新文献

{"title":"Evaluating the risk of digestive system cancer in autoimmune disease patients: a systematic review and meta-analysis focusing on bias assessment.","authors":"Julia Reizner, Simone Fischer, Jakob Linseisen, Christa Meisinger, Dennis Freuer","doi":"10.1016/j.eclinm.2025.103410","DOIUrl":"10.1016/j.eclinm.2025.103410","url":null,"abstract":"<p><strong>Background: </strong>There is emerging evidence that certain autoimmune diseases can modulate the risk for digestive system cancer. However, limitations of non-experimental studies may lead to diverging results. Thus, the aim was to evaluate the available evidence and provide bias-minimized estimates for the associations between celiac disease (CD), systemic lupus erythematosus (SLE), multiple sclerosis (MS), and type 1 diabetes (T1D) and different digestive system cancers.</p><p><strong>Methods: </strong>Systematic review (PROSPERO: CRD42024553216) was conducted according to PRISMA guidelines. Scientific publications were searched in PubMed, Web of Science, Embase, and Cochrane Library from inception up to May 2, 2025, with no restrictions on publication date. ROBINS-E tool was used for examining the study-specific risk of bias. Inverse-variance weighted random-effects models were performed as the primary meta-analytic approach. Heterogeneity was quantified and adjusted for in a comprehensive bias assessment including several analyses.</p><p><strong>Findings: </strong>This study included 237 estimates from 47 studies covering over 1.5 million cases of any ethnicity. CD, SLE, and T1D were positively associated with pancreatic, esophageal, colon, liver, and hepatobiliary cancers. Additionally, T1D was positively associated with stomach and colorectal cancers. The strongest bias-corrected association was found between CD and small intestine cancer (RR = 4.19; 95% CI: [2.71; 6.50]). MS was inversely associated with pancreatic, esophageal, rectal, and colorectal cancers.</p><p><strong>Interpretation: </strong>This study provides new insights into the evidence for digestive system cancer risk related to autoimmune diseases by adjusting for multiple sources of bias. As a next step, potential mechanisms responsible for the different associations should be investigated.</p><p><strong>Funding: </strong>The study received academic funding from the Faculty of Medicine, University of Augsburg, Germany.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103410"},"PeriodicalIF":10.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871993","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":"Prevalence of locoregional and distant lymph node metastases in children and adolescents/young adults with soft tissue sarcomas: a Bayesian meta-analysis of proportions.","authors":"Illya Martynov, Luca Tobi, Annika Strömer, Andreas Mayr, Amadeus T Heinz, Martin Ebinger, Monika Sparber-Sauer, Joerg Fuchs, Reza M Vahdad, Guido Seitz","doi":"10.1016/j.eclinm.2025.103390","DOIUrl":"10.1016/j.eclinm.2025.103390","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The presence of both regional and distant lymph node metastases (LNM) in paediatric and adolescent/young adult (AYA) patients with soft tissue sarcomas (STS) significantly impacts clinical outcomes. However, reported rates of LNM vary widely across the literature and are often accompanied by substantial uncertainty. We aimed to quantitatively synthesise global proportions of LNM across different histological subtypes and tumour sites in this population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this meta-analysis, we systematically searched MEDLINE, Scopus, and Web of Science from inception until May 1, 2024 (updated on June 1, 2025) for studies published in English that reported LNM rates in patients with STS aged 0-21 years. Eligible study designs included cohort studies, case-control studies, case series, and randomised controlled trials. Patient-level data were not requested from study authors. LNM had to be confirmed clinically, by imaging, or histologically. We excluded reviews, editorials, and case reports with fewer than three patients. We conducted a random-effects Bayesian meta-analysis using a logit transformation to synthesise LNM proportions. The posterior distributions of LNM prevalence were summarised by the posterior mean and 95% credible intervals (CrIs). Study quality was assessed across seven domains: confounding, participant selection, exposure classification, deviations from intended exposures, missing data, outcome measurement, and selective reporting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Of 3969 records screened, 263 articles were included in the data synthesis. These comprised 147 studies on rhabdomyosarcoma (RMS), 106 on non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and 10 on mixed RMS/NRSTS cohorts, representing 53,093 patients with STS. The pooled posterior mean proportion of LNM in patients with RMS (n = 41,547) was 0.228 (95% CrI: 0.202-0.255), with the highest rates observed in patients with alveolar RMS (posterior mean proportion: 0.370; 95% CrI: 0.276-0.473). Subgroup analysis by RMS primary site revealed the highest LNM rates in the perianal/perineal region (0.466; 95% CrI: 0.397-0.537), extremity (0.281; 0.210-0.363), and non-parameningeal head/neck region (0.259; 0.167-0.376). Among patients with NRSTS (n = 11,546), the pooled posterior mean proportion of LNM was 0.111 (95% CrI: 0.092-0.133), with desmoplastic small round cell tumour (0.440; 0.335-0.552), clear cell sarcoma (0.212; 0.163-0.275), and malignant rhabdoid tumour (0.199; 0.141-0.273) showing the highest rates. Most analyses had moderate-to-high heterogeneity (95% CrI for tau: 0.7443-1.1139).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Our Bayesian meta-analysis synthesises global evidence on the prevalence of LNM in paediatric and AYA patients with STS, highlighting the significant heterogeneity in LNM rates by histological subtype, particularly in NRSTS, and by tumour location, especially in RMS. Future studies should aim to stan","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103390"},"PeriodicalIF":10.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871995","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":"A simple VA-ECMO bundle in adult patients with cardiogenic shock: an analysis of ELSO registry.","authors":"Liangshan Wang, Kexin Wang, Yan Wang, Feng Yang, Chenglong Li, Xing Hao, Zhongtao Du, Peter T Rycus, Joseph E Tonna, Eddy Fan, Hong Wang, Xiaotong Hou","doi":"10.1016/j.eclinm.2025.103423","DOIUrl":"10.1016/j.eclinm.2025.103423","url":null,"abstract":"<p><strong>Background: </strong>The optimal management strategy for patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock (CS) remains uncertain. To evaluate the impact of \"bundled\" physiologic targets on outcomes in VA-ECMO patients.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed data from the Extracorporeal Life Support Organization (ELSO) registry, including adult patients receiving VA-ECMO for CS between 2013 and 2022. Patients were grouped by whether they received the full set of bundle components within the first 24 h. The bundle included mean arterial pressure > 65 mmHg, PaO₂ 60-150 mmHg, relative change in PaCO₂ [RelΔCO₂] > -50% (RelΔCO₂ = [(PaCO_2-24hours-PaCO_2-baseline)/PaCO_2-baseline] ∗ 100%), and peak inspiratory pressure < 30 mmHg. The primary outcome was survival to hospital discharge, while secondary outcomes were complications.</p><p><strong>Findings: </strong>Of 7950 patients (mean age 56.5 ± 14.3 years), 2762 (34.7%) received the complete bundle. The bundle group had significantly higher rates of survival to hospital discharge (55.9% vs. 39.4%, <i>p</i> < 0.001) with adjusted odds ratio [aOR] of 1.849 (95% CI [1.675, 2.042]; <i>p</i> < 0.001), and the likelihood of brain death (aOR = 0.521, 95% CI: 0.289-0.885; <i>p</i> = 0.021), ischemic stroke (aOR = 0.710, 95% CI: 0.559-0.896; <i>p</i> = 0.004), hemorrhagic complications (aOR = 0.773, 95% CI: 0.681-0.876; <i>p</i> < 0.001) and cardiovascular complications (aOR = 0.863, 95% CI: 0.770-0.966; <i>p</i> = 0.011) were reduced.</p><p><strong>Interpretation: </strong>Achieving the proposed physiologic bundle is associated with improved survival and a reduced risk of complications in VA-ECMO patients with CS. These findings provide evidence supporting the use of standardized care bundles in the management of VA-ECMO patients with CS.</p><p><strong>Funding: </strong>This work was supported by the Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (No. ZYLX202111, to X Hou), Beijing Hospitals Authority \"Ascent Plan\" (No. FDL20190601, to X Hou), Young Elite Scientists Sponsorship Program by CAST (No. 2022QNRC001, to L Wang), National Natural Science Foundation of China (No. 82200433, to L Wang), and Beijing Hospitals Authority Youth Programme (No. QML20230602, to L Wang), National Natural Science Foundation of China (No. 82100408, to X Hao), Beijing Nova Program (No. 2022064, to C Li), Beijing Natural Science Foundation (No. 7244327, to C Li), and the National Key Research and Development Program of China (No. 2021YFC2701700 and 2021YFC2701703, to Z Du).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103423"},"PeriodicalIF":10.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871991","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":"Switch to mania after acute antidepressant treatment for bipolar depression: a systematic review and network meta-analysis of randomised controlled trials.","authors":"Vincenzo Oliva, Michele De Prisco, Enrico La Spina, Sofia Paolucci, Giovanna Fico, Gerard Anmella, Diego Hidalgo-Mazzei, Andrea Murru, Maurizio Pompili, Michele Fornaro, Marco Solmi, Ayşegül Yildiz, Stefan Leucht, Eduard Vieta, Joaquim Radua","doi":"10.1016/j.eclinm.2025.103413","DOIUrl":"10.1016/j.eclinm.2025.103413","url":null,"abstract":"<p><strong>Background: </strong>The potential for antidepressants to induce a switch to mania remains a major concern in the treatment of bipolar depression, but the specific risk associated with different antidepressants remains unclear. This systematic review and network meta-analysis (NMA) assessed this risk by comparing individual antidepressants with each other and with a common placebo.</p><p><strong>Methods: </strong>In this systematic review and network meta-analysis, we searched ClinicalTrials.gov, CENTRAL, PsycINFO, PubMed, Scopus, and Web of Science from database inception up to Feb 19, 2025, with no language restrictions, for randomised controlled trials (RCTs) assessing acute antidepressant treatment in bipolar depression. The primary outcome was the rate of switch to mania after antidepressant treatment. A frequentist NMA estimated risk ratios (RRs) and 95% confidence intervals. Sensitivity analyses were performed based on treatment regimen (monotherapy or add-on), baseline severity, switch to mania definition, study setting, psychiatric comorbidity, treatment duration, non-pharmacological combinations, industry sponsorship, and risk of bias. Certainty of evidence was assessed using the CINeMA framework. The protocol was preregistered on the Open Science Framework.</p><p><strong>Findings: </strong>Of 2434 records screened, 13 RCTs (1362 patients; 818 [60.1%] female, 511 [37.5%] male, and 33 [2.4%] not disclosed) were included in the NMA. Although some evidence of increased risk of switching to mania was observed, no antidepressant was associated with a significantly higher risk of switch to mania compared to placebo. Venlafaxine showed the highest risk estimate among antidepressants, though not statistically significant RR (4.53 [95% CI 0.47-43.25]), and was the only compound with consistent signals of increased switch in individual studies. The evidence base was larger for add-on therapy, while fewer data were available for monotherapy. Sensitivity analyses confirmed the results. Heterogeneity was low. Overall confidence in the evidence was rated as low.</p><p><strong>Interpretation: </strong>Antidepressants remain a treatment option for acute bipolar depression, particularly as add-on therapy. Their use should be individualised, considering patient-specific profiles and other potential risks, in line with a precision psychiatry approach. Further studies are needed to clarify long-term safety.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103413"},"PeriodicalIF":10.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871998","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":"Quality of antidiabetic medicines in 13 sub-Saharan African countries: a cross-sectional survey.","authors":"Marie Antignac, Roland N'Guetta, Philippe Henri Secretan, Bernard Do, Meo Stephane Ikama, Jean Bruno Mipinda, Ibrahim Ali Toure, Jean Laurent Takombe, Yves Lubenga, Mouhamadoul Mounir Dia, El Bou Isselmou Boukhary Ould, Maxwell Dalaba, Naby Moussa Balde, Amadou Kake, Ely Cheikh Ibrahima Sy, Pauline Cavagna, Marie Cécile Perier, Eugène Sobngwi, Pr Badara Cisse, Christian Boitard, J P Empana, I Bara Diop, Maimouna Ndour Mbaye, Xavier Jouven","doi":"10.1016/j.eclinm.2025.103405","DOIUrl":"10.1016/j.eclinm.2025.103405","url":null,"abstract":"<p><strong>Background: </strong>The burden of diabetes is rising dramatically in low- and middle-income countries. The menace of substandard and falsified drugs constitutes a major hazard that compromises healthcare. The DIABDAF study aimed to assess the quality of routinely used antidiabetic drugs including oral drugs and insulins in sub-Saharan Africa.</p><p><strong>Methods: </strong>Drugs were collected in 13 sub-Saharan African cities in licensed and unlicensed places of sales between February 2020 and March 2023. Chemical analyses were conducted blindly in a public laboratory following recommended good laboratory practices. Drug quality was classified based on the ratio of measured to expected active ingredient dosage: 95-105% as good (A), 85-94·99% or 105·01-115% as low (B), and below 85% or above 115% as very low (C). Impurity levels were assessed using thresholds from the United States and European Pharmacopoeias monographs.</p><p><strong>Findings: </strong>A convenient samples of 4951 antidiabetic drugs were collected from 13 sub-Saharan African countries (Seven middle-income and six low-income countries). Out of the 1673 (of 4951 collected) drug samples randomly tested, 28·0% (<i>n</i>: 468, 95% CI [22·3-33·0]) failed to meet standards related to the expected content of active ingredients (B: 27·2% 95% CI [21·5-32·0]; C: 0·8% 95% CI [0·2-3·5]), with more samples showing underdosage (19·31% 95% CI [14·8-24·3]) than overdosage (8·67% 95% CI [5·3-12·5]). Impurity levels were excessive in 9·68% (<i>n</i>: 162, 95% CI [6·0-14·8]) of samples. Overall, 32·8% (<i>n</i>: 548, 95% CI [26·5-38·1]) were deemed to be of poor quality according to active ingredient content or impurity level. In multivariate logistic regression, factors associated with worse quality were drugs, expired status, and country of purchase.</p><p><strong>Interpretation: </strong>In this multinational study assessing the quality of antidiabetic drugs in sub-Saharan Africa, we found a significant proportion of poor-quality drugs. National health authorities must take action to ensure access to safe, high-quality medications for diabetic patients.</p><p><strong>Funding: </strong>DIABDAF study was exclusively supported by French public grant (INSERM, AVIESAN, AP-HP, and University of Paris Cité).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103405"},"PeriodicalIF":10.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of HH2853, a novel EZH1/2 dual inhibitor, in patients with refractory solid tumours or non-Hodgkin lymphomas: a phase I study.","authors":"Zhengfu Fan, Jin Wang, Dan Liu, Lin Shen, Meiyu Fang, Patrick Johnson, Han Tun, David Sommerhalder, Jilong Yang, Yun Yang, Javier Munozi, Jun Zhu, Tian Gao, Zhiming Li, Xian'an Li, Qiuying Ma, Chao Lv, Songda Yu, Fugen Li, Yuqin Song, Jifang Gong","doi":"10.1016/j.eclinm.2025.103398","DOIUrl":"10.1016/j.eclinm.2025.103398","url":null,"abstract":"<p><strong>Background: </strong>HH2853 is a novel dual EZH1/2 inhibitor that exhibits superior antitumour activity compared to tazemetostat across various preclinical models. Here, we evaluated the safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy of HH2853 in patients with refractory advanced solid tumours and non-Hodgkin lymphomas (NHLs).</p><p><strong>Methods: </strong>This open-label, global multicentre, phase I study was conducted at 12 centres in China and the USA, enrolling patients (aged ≥18 years) with relapsed or refractory solid tumours or NHLs. For dose escalation, seven predefined dose levels of HH2853 (50, 100, 200, 400, 600, 800, 1000 mg, orally twice daily for 28 days) were evaluated using a standard Bayesian optimal interval with accelerated titration design. Two dose levels were selected for dose extension. Primary endpoints were safety, dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included PK/PD profiles and preliminary efficacy. This study is registered with ClinicalTrials.gov, NCT04390737.</p><p><strong>Findings: </strong>Between Sept 8, 2020, and Feb 28, 2023, 61 patients received HH2853. As of Jan 5, 2024, the median follow-up was 15.7 months (interquartile range [IQR], 13.8-17.7). Two DLTs were observed in patients at 800 mg dose level. MTD was not reached. The dose levels of 400 mg and 600 mg were selected for dose extension, and the RP2D was determined as 400 mg twice daily. Treatment-related adverse events (TRAEs) of any grade occurred in 58 patients (95.1%). The most common TRAEs were diarrhoea (n = 31, 50.8%), blood bilirubin increased (n = 29, 47.5%) and anaemia (n = 23, 37.7%). The most common TRAEs of grade ≥3 included anaemia (n = 7, 11.5%), diarrhoea (n = 5, 8.2%), and platelet count decreased (n = 4, 6.6%). No treatment-related deaths were reported. Among 57 efficacy-evaluable patients, 17 (27.9%) achieved an objective response, with four complete responses and 13 partial responses. Ten of 17 objective responses (58.8%) were observed in patients with epithelioid sarcoma (ES). The objective response rate in patients with ES was 31.3% (95% confidence interval [CI], 16.0-50.0), and the median progression-free survival was 16.0 months (95% CI, 5.2-19.1).</p><p><strong>Interpretation: </strong>HH2853 showed a manageable safety profile and encouraging antitumour activity in refractory solid tumours and NHLs, with particularly promising antitumour activity in ES. Further trials are needed. A phase II trial of HH2853 in patients with ES is underway.</p><p><strong>Funding: </strong>The Science, Technology and Economic Commission of Shanghai Pudong New Area Municipality and Shanghai Haihe Biopharma Co., Ltd.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103398"},"PeriodicalIF":10.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871990","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":"Management of <i>Clostridioides difficile</i> infection in patients with haematological malignancies and after cellular therapy: guidelines from 10th European Conference on Infections in Leukaemia (ECIL-10).","authors":"Malgorzata Mikulska, Christine Robin, Dionysios Neofytos, Chiara Oltolini, Agnieszka Piekarska, Elena Reigadas, Lidia Gil, Roy F Chemaly, Andreas H Groll, Patricia Muñoz, Benjamin W Teh","doi":"10.1016/j.eclinm.2025.103371","DOIUrl":"10.1016/j.eclinm.2025.103371","url":null,"abstract":"<p><p><i>Clostridioides difficile</i> infection (CDI) poses a significant challenge in patients with haematological malignancies (HM) and those undergoing cellular therapy such as haematopoietic cell transplantation (HCT) or CAR T-cell therapy. These patients have high rates of both colonization with <i>Clostridioides difficile</i> and diarrhoea due to non-infectious causes, leading to challenges with establishing diagnosis and optimal management of CDI, especially in the setting of molecular detection of toxin genes alone. Current severity criteria are of limited usefulness since underlying haematological disease and its treatment impact white blood count and inflammatory manifestations of severe CDI. Extensive exposure to antibiotics, profound microbiota damage and bidirectional relationship with gastro-intestinal graft-versus-host disease after transplant further complicate clinical management. Therefore, the 10th European Conference on Infections in Leukemia (ECIL-10) group comprehensively reviewed the literature (published 01/01/2010-15/09/2024) on the epidemiology, treatment and prevention of CDI, and formulated consensus recommendations for the management of CDI specific to this population. New definitions of proven, probable and possible CDI in this population were developed and proposed for use in clinical research to standardise reporting.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103371"},"PeriodicalIF":10.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871994","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":"Regional lymph node invasion in pediatric non-rhabdomyosarcoma soft tissue sarcoma: an international cohort study from the International Soft Tissue Sarcoma Consortium.","authors":"Daniel Orbach, Matthieu Carton, Amadeus T Heinz, Lise Borgwardt, J Herve Brisse, Carlo Morosi, Erin R Rudzinski, Akmal Safwat, Monika Sparber-Sauer, Stephanie Terezakis, Andrea Ferrari, Aaron R Weiss, William H Meyer, David O Walterhouse, Timothy B Lautz","doi":"10.1016/j.eclinm.2025.103409","DOIUrl":"10.1016/j.eclinm.2025.103409","url":null,"abstract":"<p><strong>Background: </strong>In pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), the frequency and prognostic impact of regional lymph node involvement (N1) are not clearly defined and may vary according to histological type. We therefore to analyze the rate of N1 at diagnosis, the pattern of nodal relapse, and the prognostic impact of N1 in pediatric patients with NRSTS.</p><p><strong>Methods: </strong>Data were collected and analyzed through the International Soft Tissue SaRcoma ConsorTium (INSTRuCT). Patients aged 0-21 years with NRSTS prospectively enrolled in European and North American cooperative group trials from October 1, 1990 to October 1, 2018 were included. Descriptive statistics, logistic regressions, and Cox proportional hazards models were used to analyze the data and assess prognostic factors.</p><p><strong>Findings: </strong>1937 patients were eligible for inclusion. The main histotypes were synovial sarcoma (628 cases; 32%), undifferentiated/unclassified sarcoma (396 cases, 20%) and malignant peripheral nerve sheath tumor (275 cases, 14%). Distant metastases were present in 197 (10.2%) patients. N1 was present in 152 (7.8%) patients. With a median follow-up of 7.2 years (95% CI 7.0-7.4), 615 patients (31.7%) had local relapse or progression, 30 (1.5%) had nodal relapse (including four with initial N1), and 287 (14.8%) developed metastases. In multivariate analysis, node positive (N1) status was associated with high pathologic grade (p = 0.010) and distant metastasis (p < 0.0001), but not with tumor size, invasiveness, and histological subgroups (p = 0.36). For non-metastatic tumors (1740 cases), metastatic-free-survival differed between node negative N0 and N1 patients, but overall survival, event-free-survival and nodal relapse-free-interval did not.</p><p><strong>Interpretation: </strong>N1 is rare in NRSTS during childhood (<8%) and mainly presents in a subset of histotypes. Regional nodal control at 5 years is adequate. However, N1 in NRSTS is a marker of aggressive disease.</p><p><strong>Funding: </strong>Cancer Research Foundation, Children's Research Foundation, Comer Development Board, KickCancer, King Baudouin Foundation, Rally Foundation for Childhood Cancer Research, Seattle Children's Foundation from Kat's Crew Guild through the Scleroderma Research Foundation, St. Baldrick's Foundation, The Andrew McDonough B+ Foundation, Maddie's Promise, Summer's Way Foundation, Friends of T.J. Foundation, Sebastian Strong, Children's Oncology Group Foundation, and the Sarah Jane Adicoff Endowment for Research in Rhabdomyosarcoma through the Seattle Children's Foundation.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"87 ","pages":"103409"},"PeriodicalIF":10.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871997","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":"Efficacy and safety of flupentixol-melitracen in patients with refractory chronic cough: a randomised, double-blinded, placebo-controlled clinical trial.","authors":"Qiang Chen, Mengru Zhang, Li Zhang, Alimire Aierken, Ran Dong, Xianghuai Xu, Li Yu, Kefang Lai, Zhongmin Qiu","doi":"10.1016/j.eclinm.2025.103367","DOIUrl":"10.1016/j.eclinm.2025.103367","url":null,"abstract":"<p><strong>Background: </strong>The antitussive potential of flupentixol-melitracen, an anti-anxiety and anti-depression compound, has been observed previously. We aimed to further evaluate its efficacy and safety in patients with refractory chronic cough (RCC) who were unresponsive to any other available treatments.</p><p><strong>Methods: </strong>This randomised, double-blinded, placebo-controlled clinical trial was conducted at a single specialist cough clinic in Tongji Hspital, Shanghai, China. Adults aged 18-69 years with RCC and persistent cough despite at least two weeks of neuromodulator therapy were enrolled. Participants were randomly assigned (1:1) to receive either oral flupentixol-melitracen (flupentixol 0.5 mg + melitracen 10 mg), one tablet twice daily, or matching placebo, for two weeks, followed by a one week of off-treatment safety monitoring. Randomisation was computer-generated, with masking of participants, investigators, and outcome assessors. The co-primary endpoints were cough resolution rate (≥50% reduction in cough symptom score [CSS]) at visit four and placebo-adjusted change in CSS over time. The full analysis set (FAS) was used following the modified intention-to-treat (mITT) principle for demographic baseline analysis and efficacy analysis. The safety set (SS) was used for safety analysis and included all patients who took at least one dose of treatment and had post-dose safety records. The FAS and SS were equivalent in this study. The trial is registered with the Chinese Clinical Trial Registry, ChiCTR2000035304.</p><p><strong>Findings: </strong>Between March 9th, 2021 and December 1st, 2023, 102 patients were enrolled and randomised. A total of 99 patients received at least one dose of treatment and were included in the primary and safety analyses (49 taking flupentixol-melitracen and 50 taking placebo). At visit four, flupentixol-melitracen arm reached significantly higher cough resolution rate (65.3% [32/49] vs 32.0% [16/50]; p = 0.0009). The adjusted mean reduction in CSS was 0.144 points greater in the flupentixol-melitracen group than in the placebo group over time (p = 0.0034). Treatment-emergent adverse events occurred in 51.0% (15/49) of patients in the flupentixol-melitracen group and 34.0% (17/50) in the placebo group. No serious adverse events or treatment-related deaths were reported. All adverse events were mild and resolved after discontinuation.</p><p><strong>Interpretation: </strong>Our findings suggest that short-term use of flupentixol-melitracen may be an effective and well-tolerated treatment for RCC. However, the findings should be interpreted with caution due to key limitations, including the absence of objective cough frequency measurement and limited generalisability beyond a single-centre population. These factors may influence the precision and applicability of the observed treatment effect. Further trials using objective endpoints and longer follow-up in broader populations are needed to ","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103367"},"PeriodicalIF":10.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845026","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":"Factors influencing the prevalence and death rate of COPD: a pan-database ecological study covering 201 countries and regions from 1990 to 2021.","authors":"Zihui Wang, Wenhan Cao, Zhixuan You, Shaoqiang Li, Mingshan Xue, Haiyang Li, Junfeng Lin, Guannan Cai, Yuqi Chen, Zhiman Liang, Chengtao Zhou, Xiaofang Wu, Guanghui Dong, Nanshan Zhong, Baoqing Sun, Zhangkai J Cheng","doi":"10.1016/j.eclinm.2025.103347","DOIUrl":"10.1016/j.eclinm.2025.103347","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is a common, heterogeneous disease and may be influenced by diverse factors. However, gaps remain in previous studies regarding the exploration of potential influencing factors. This study aims to investigate the wide range of potential factors influencing COPD based on a pan-database ecological analysis.</p><p><strong>Methods: </strong>We integrated data from 17 global databases (e.g., the Global Burden of Disease Study) which encompass social, environmental, and health data across various regions. Generalized linear regression was used to analyze the association of cumulative and instant exposures of factors with COPD and to rank their importance. Spearman analysis was used to assess the correlation of various factors with COPD. Heatmaps, scatter plots, and nonclassical multidimensional scaling (i.e., network graph) were employed to visualize the correlations.</p><p><strong>Findings: </strong>The study aggregated 77 social and environmental factors, 85 lifestyle and dietary factors, 25 physiological indicators, and 28 diseases. In the cumulative exposure analysis, tobacco consumption, atmospheric pollutants (e.g., ozone, CO, and organic matter aerosol), biomass cooking, and climatic conditions (e.g., vapor pressure, solar radiation, and temperature) were found to be associated with COPD prevalence. Additionally, tobacco consumption, social factors (e.g., hunger index, gender inequality index, and education year), and climatic conditions significantly impacted death rates. The results for cumulative exposures were consistent with those for instant exposures. Network graph analysis indicated a positive correlation between COPD and chronic kidney disease, other chronic respiratory diseases, gout, and stroke.</p><p><strong>Interpretation: </strong>Various factors (e.g., tobacco consumption, atmospheric pollution, biomass cooking, temperature, social factors, and comorbidities) significantly influence COPD. Comprehensive interventions are needed to reduce the disease burden of COPD.</p><p><strong>Funding: </strong>The Foundation of Guangzhou National Laboratory (SRPG22-018, SRPG22-016), State Key Laboratory of Respiratory Disease (SKLRD-OP-202402), Zhejiang medical health science and technology project (2025KY1245), Multi-Center Clinical Research Project of Guangzhou Medical University (GMUCR2025-02009), and Guangzhou Municipal Science and Technology Bureau (SL2024A04J00706).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103347"},"PeriodicalIF":10.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820918","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}