EClinicalMedicine最新文献

{"title":"The expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions.","authors":"Areesha Moiz, Kristian B Filion, Michael A Tsoukas, Oriana H Y Yu, Tricia M Peters, Mark J Eisenberg","doi":"10.1016/j.eclinm.2025.103363","DOIUrl":"10.1016/j.eclinm.2025.103363","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed obesity management, offering substantial weight loss and metabolic benefits. This review examines their expanding role, evaluating efficacy compared to alternative treatments, emerging indications, ongoing challenges, and future directions. Beyond obesity and type 2 diabetes, the therapeutic potential of GLP-1 RAs extends to a range of conditions such as cardiovascular disease, liver disease, neurodegenerative disease, and substance abuse disorders. While early concerns regarding pancreatic and thyroid cancer have been largely attenuated by recent evidence, issues such as gallbladder and biliary disorders, psychiatric safety, and perioperative aspiration risk require ongoing investigation. Additionally, observations of weight regain after treatment discontinuation and reductions in lean mass highlight the need for long-term, individualized strategies to sustain clinical benefits. The high cost and limited access to these medications raise critical policy and equity challenges. Future research must address these gaps, focusing on long-term safety, optimizing combination approaches, and evaluating the broader clinical and economic implications of widespread GLP-1 RA use.</p><p><strong>Funding: </strong>K.B.F. is supported by a William Dawson Scholar award from McGill University. T.M.P. is a Fond de Recherche du Québec-Santé (FRQS) research scholar. M.J.E. holds a James McGill Professor award from McGill University. The funding sources had no involvement in the conduct of this study, interpretation of results, or the preparation of this manuscript for publication.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103363"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal timing and mode of planned birth for term, large infants: a retrospective, population-based cohort study.","authors":"Georgia Anne Santomartino, Kylie Crawford, Jesrine Hong, Sailesh Kumar","doi":"10.1016/j.eclinm.2025.103366","DOIUrl":"10.1016/j.eclinm.2025.103366","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Large infants (birthweight &gt; 75th centile) are at increased risk of mortality, severe neonatal neurological and non-neurological morbidity. We aimed to ascertain the optimal method and gestation of planned birth (scheduled caesarean section or induction of labor) that were associated with lower odds of adverse outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This was a retrospective cohort study of term singleton births with birthweight &gt;75th centile between January 2000 and December 2021 in Queensland, Australia. Primary outcomes were severe adverse maternal outcome, perinatal mortality (intrapartum stillbirth or neonatal death), severe neonatal neurological morbidity, and other severe neonatal morbidity. Multivariable logistic regression models were built to determine odds ratios (OR) for the effect of timing of both methods of planned birth on adverse outcomes. Induction of labor at 38&lt;sup&gt;+0&lt;/sup&gt;-38&lt;sup&gt;+6&lt;/sup&gt; weeks was the referent category because many international guidelines recommend this as the optimum timing of birth.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;There were 151,464 planned births for large infants. 86,515 (57.1%) were induction of labor while 64,949 (42.9%) were scheduled caesarean section. Compared to induction of labor at 38&lt;sup&gt;+0&lt;/sup&gt;-38&lt;sup&gt;+6&lt;/sup&gt; weeks, induction at ≥41&lt;sup&gt;+0&lt;/sup&gt; weeks (aOR 1.28, 95% CI 1.21, 1.35) and scheduled caesarean section at 37&lt;sup&gt;+0&lt;/sup&gt;-37&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 1.18, 95% CI 1.08, 1.28) were associated with greater odds of severe adverse maternal outcome, whilst scheduled caesarean section at 39&lt;sup&gt;+0&lt;/sup&gt;-39&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 0.75, 95% CI 0.70, 0.80) was associated with lower odds of this outcome. The odds of severe neonatal neurological morbidity were lower following induction at 40&lt;sup&gt;+0&lt;/sup&gt;-40&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 0.72, 95% CI 0.59, 0.89) or scheduled caesarean section at 37&lt;sup&gt;+0&lt;/sup&gt;-37&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 0.59, 95% CI 0.43, 0.81), 39&lt;sup&gt;+0&lt;/sup&gt;-39&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 0.26, 95% CI 0.2, 0.33), and ≥41&lt;sup&gt;+0&lt;/sup&gt; weeks (aOR 0.31, 95% CI 0.13, 0.75) respectively. For other severe neonatal morbidity, the odds were highest after induction of labor at 37&lt;sup&gt;+0&lt;/sup&gt;-37&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 1.35, 95% CI 1.24, 1.46), and lowest following scheduled caesarean section at 40&lt;sup&gt;+0&lt;/sup&gt;-40&lt;sup&gt;+6&lt;/sup&gt; weeks (aOR 0.31, 95% CI 0.26, 0.36). There were no significant differences in perinatal mortality based on method of planned birth or gestational age.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;In our cohort, scheduled caesarean section between 39&lt;sup&gt;+0&lt;/sup&gt;-39&lt;sup&gt;+6&lt;/sup&gt; weeks for large infants at birth was associated with lower odds of severe adverse maternal outcomes, severe neonatal neurological morbidity, and other severe neonatal morbidity compared to induction of labor at 38&lt;sup&gt;+0&lt;/sup&gt;-38&lt;sup&gt;+6&lt;/sup&gt; weeks. For women that underwent induction of labor, the odds of emergency caesarean section were lowest at 39&lt;sup&gt;+0&lt;/sup&gt;-39&lt;sup&gt;","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103366"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing of intravenous iron for treatment of anaemia in surgical patients: a systematic review and network meta-analysis.","authors":"Chang Liu, Jiashu Han, Renkui Fu, Tianyu Li, Georgios Antonios Margonis, Jaeyun Jane Wang, Kaiqi Ma, Weibin Wang, Chen Lin","doi":"10.1016/j.eclinm.2025.103361","DOIUrl":"10.1016/j.eclinm.2025.103361","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Anaemia complicates recovery in surgical patients. Intravenous (IV) iron supplementation shows promise in improving outcomes, but optimal timing remains uncertain. In this review, we compare the efficacy, safety, tolerability, and outcomes between preoperative and postoperative IV iron supplementation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this systematic review and network meta-analysis, we searched PubMed, EMBASE, Cochrane Library, and Web of Science from inception to May 1, 2025, for randomised controlled trials (RCT) investigating IV iron supplementation in surgical patients either 7-30 days before surgery (preoperative) or 0-30 days after surgery (postoperative). Studies were excluded if they included patients with critical illness or prior transfusion or if iron was given outside the defined time frames or with other agents. Two reviewers independently appraised the data and extracted summary estimates from published reports. The primary outcomes were: (1) proportion of patients who received blood transfusion; (2) change between the baseline haemoglobin level and the haemoglobin level on postoperative day (POD) 7 and POD30. Data processing was conducted based on frequentist network meta-analysis. The risk of bias was assessed using the Cochrane Risk of Bias tool. The protocol is registered with PROSPERO, CRD42024533265.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Among 129 identified studies, 22 RCTs with 3026 patients were included. All included studies had a low (n = 6) or moderate (n = 16) risk of bias. Compared to controls, postoperative IV iron supplementation reduced transfusion rates (RR 0.80, 95% CI 0.68-0.94; I&lt;sup&gt;2&lt;/sup&gt; = 0.0%). Postoperative IV iron supplementation did not affect haemoglobin levels (MD -4.51, 95% CI -9.75 to 0.72; I&lt;sup&gt;2&lt;/sup&gt; = 90.3%) at POD7 but increased haemoglobin levels (MD 5.45, 95% CI 2.70-8.20; I&lt;sup&gt;2&lt;/sup&gt; = 45.5%) at POD30. In comparison, preoperative IV iron supplementation resulted in higher haemoglobin levels than postoperative supplementation at POD30 (MD 6.67, 95% CI 1.61-11.72) but did not influence transfusion rates (RR 0.91, 95% CI 0.72-1.15; I&lt;sup&gt;2&lt;/sup&gt; = 0.0%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Our results suggest that postoperative IV iron supplementation reduces transfusion rates, while preoperative supplementation improves haemoglobin recovery. Clinicians may choose either strategy in an individualised, patient-centered manner. These conclusions should be interpreted with caution due to heterogeneity among included studies, limited data for subgroup analyses, and the absence of direct comparisons between preoperative and postoperative approaches.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;National Key Research and Development Program of China, National Natural Science Foundation of China, Beijing Natural Science Foundation, Capital's Funds for Health Improvement and Research, National High Level Hospital Clinical Research Funding, and Chinese Academy of Medical Sciences I","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103361"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a novel prognostic model to predict 1-year post-transplant mortality for acute-on-chronic hepatitis B liver failure: a nationwide, multicentre, cohort study.","authors":"Li Zhuang, Yimou Lin, Yu Jia, Jun Fang, Yujian Zheng, Taishi Fang, Meiching Ong, Aibo Mu, Jiaxing Zhu, Mengchao Wang, Dong Zhao, Feiwen Deng, Qiucheng Lei, Leibo Xu, Zuozhong Yang, Qiang Sun, Wei Qu, Chenwei Xu, Zhijun Zhu, Chuanjiang Li, Hanyu Jiang, Jimin Liu, Xiaoshun He, Shusen Zheng, Zhiyong Guo, Qi Ling","doi":"10.1016/j.eclinm.2025.103365","DOIUrl":"10.1016/j.eclinm.2025.103365","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Liver transplantation (LT) provides a potential cure for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop and externally validate a prognostic model to predict 1-year post-LT mortality in patients with HBV-ACLF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This retrospective, nationwide, observational cohort study was conducted at ten high-volume LT centres in China. 4378 adult patients who underwent primary LT between January 2015 and December 2021 were screened, and those with HBV-ACLF according to the COSSH-ACLF criteria (separated into three ACLF grades based on the number of organ failures) were included. The HBV-ACLF LT (HALT) model was developed in the derivation cohort and validated in the external testing cohort. The derivation cohort were derived from two LT centres in one province (Zhejiang). The external testing cohort were derived from eight LT centres in two provinces. For model development, univariable Cox regression analysis was used to identify risk factors associated with 1-year post-LT mortality. Variables with univariable &lt;i&gt;p&lt;/i&gt; &lt; 0.05 were entered into the least absolute shrinkage and selection operator (Lasso) analysis for further feature selection. 10-fold cross validation was used to choose the optimal lambda (penalty for the number of features) of the Lasso model. Multivariable Cox regression was applied to construct the HALT model based on the risk factors selected by Lasso analysis. Primary outcome was survival rate at 1-year after LT. Secondary outcomes were short-term (28- and 90-day) and long-term survival after LT (3- and 5-year). Model performance was compared with eight other models (COSSH-ACLF II, COSSH-ACLF, CLIF-C ACLF, AARC, MELD, MELD-Na, SALT-M and TAM scores), using receiver operating characteristic curve and C-index values. A nomogram was developed to analyse the probability of the primary outcome in different graft-recipient combinations based on recipient factors (age, number of organ failures [OF], lactate) and graft factors (donation after circulatory death [DCD] and cold ischaemia time [CIT]).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between Jan 1, 2015, and Dec 1, 2021, 668 patients were included (derivation cohort, n = 418; external testing cohort, n = 250), with survival rates of 88.0%, 81.1%, 77.5%, 75.6% and 72.1% at 28-day, 90-day, 1-year, 3-year and 5-year post-LT, respectively. Three recipient's factors (age, number of OF and arterial lactate concentration) as well as two graft's parameters (DCD and CIT) were independently associated with 1-year post-LT mortality in the derivation cohort (all &lt;i&gt;p&lt;/i&gt; &lt; 0.05). The HALT model was established accordingly, showing better discriminative performance (C-index, 0.791) than eight current models in the external testing cohort (C-index, 0.529-0.627; all &lt;i&gt;p&lt;/i&gt; &lt; 0.001). If the sickest patients (age &gt;55 years, OFs ≥3 and lactate ≥2.5 mmol/L) received high-risk grafts (DCD and CIT &gt;10 h), the estimate","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103365"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728671","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":"Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysis.","authors":"C A Smith, S Y Bögli, M M Placek, M Cabeleira, D White, E Daubney, A Young, E Beqiri, R Kayani, R O'Donnell, N Pathan, S Watson, A Maw, M Garnett, H K Kanthimathinathan, H Bangalore, S Sundararajan, G Subramanian, D Raffaj, S Lampariello, A Sarfatti, A Mayer, O Ross, M Czosnyka, P J Hutchinson, P Smielewski, S Agrawal","doi":"10.1016/j.eclinm.2025.103370","DOIUrl":"10.1016/j.eclinm.2025.103370","url":null,"abstract":"<p><strong>Background: </strong>Cerebral perfusion pressure (CPP) represents a key target for intensive care management of paediatric traumatic brain injury (TBI) patients. Current guidelines recommend a CPP target within the range of 40-50 mmHg but emphasise that these may depend on patient age and the state of cerebrovascular autoregulation. In this analysis, we aimed to compare the fixed targets proposed by the Brain Trauma Foundation to autoregulation-based targets CPPopt (optimal CPP) and LLA (Lower Limit of Autoregulation).</p><p><strong>Methods: </strong>Data were acquired from the STARSHIP study (a prospective, multicentre, observational, research study which enrolled 135 children (median age 96 months (interquartile range 26-152 months)) with TBI between July 2018 and March 2023 across 10 paediatric intensive care units in the UK). In this secondary analysis the dose or percentage time spent below a fixed CPP target of 50 mmHg or CPPopt or LLA (assessed continuously on a minute-by-minute basis and derived by fitting a curve to the relationship between CPP and pressure reactivity index values, as previously described) was compared by outcome using univariable and multivariable methods. ClinicalTrials.gov registration-NCT0688462.</p><p><strong>Findings: </strong>When assessed within ordinal analyses (to account for differences in baseline severity), both hourly dose and percentage time spent below LLA (odds ratio 1.01 [95% CI 1.00-1.02], p = 0.017 and 1.05 [95% CI 1.01-1.08], p = 0.008 respectively) were independently associated with worse outcomes. LLA displayed a dynamic time-trend increasing over time in patients with unfavourable outcome (n = 44, p = 0.003). Overall, LLA exceeded 50 mmHg for more than 45% of the monitoring period across all patients, and for over 35% of the time in the youngest cohort (0-2 years).</p><p><strong>Interpretation: </strong>Dynamic autoregulation monitoring based on LLA was associated with outcomes in paediatric TBI with higher LLA values observed in individuals experiencing unfavourable outcomes. Our findings indicate that the current fixed CPP threshold of 40-50 mmHg may be too low-highlighting the need for further investigation into autoregulation-guided CPP targets. Whether personalised management based on autoregulatory-informed thresholds offers advantages over guideline-based targets remains to be determined and should be investigated in future prospective interventional studies.</p><p><strong>Funding: </strong>Action Medical Research for Childrens' Charity and Addenbrookes Charitable Trust (UK Grant number-GN2609).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103370"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728681","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":"Exploring personalized neoadjuvant therapy selection strategies in breast cancer: an explainable multi-modal response model.","authors":"Luyi Han, Tianyu Zhang, Anna D'Angelo, Anna van der Voort, Katja Pinker-Domenig, Marleen Kok, Gabe Sonke, Yuan Gao, Xin Wang, Chunyao Lu, Xinglong Liang, Jonas Teuwen, Tao Tan, Ritse Mann","doi":"10.1016/j.eclinm.2025.103356","DOIUrl":"10.1016/j.eclinm.2025.103356","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant therapy (NAT) regimens for breast cancer are generally determined according to cancer stage and molecular subtypes without fully considering the inter-patient variability, which may lead to inefficiency or overtreatment. Artificial intelligence (AI) may support personalized regimen recommendations by learning the synergistic relationship between pre-NAT individual-patient data, regimens, and corresponding short- or long-term therapy responses.</p><p><strong>Methods: </strong>In this retrospective study, we collected data from breast cancer patients treated with NAT between 2000 and 2020 from the Netherlands and the USA. Median follow-up times ranged from 3·7 to 4·9 years across molecular subtypes and cohorts. We developed and externally validated a multi-modal model integrating pre-NAT clinical data, dynamic contrast enhanced (DCE)-MRI images, and medical reports to predict pathological complete response (pCR) and likelihood of survival after NAT. We subsequently evaluated potential benefits for patients receiving a personalized regimen recommended based on these predictions.</p><p><strong>Findings: </strong>We trained our model on 655 patients and validated it on internal (655 patients) and external (241 patients) cohorts. Given the factual regimens, the model can correctly predict the corresponding therapy response, with areas under the receiver operating characteristic curves (AUC) of 0·80 (95% CI 0·73-0·87), 0·75 (0·66-0·83), and 0·85 (0·77-0·92) for pCR prediction of human epidermal growth factor receptor 2 (HER2)+, triple-negative, and estrogen receptor/progesterone receptor (ER/PR)+&HER2- patients in the internal validation cohort, respectively. Performance in the external validation cohort was 0·707 (0·557-0·836), 0·558 (0·359-0·749), and 0·860 (0·767-0·945) for the corresponding molecular subtypes, respectively. In the internal validation cohort, survival prediction identified high-risk patients across different molecular subtypes, as demonstrated by a hazard ratio (HR) of 3·29 (0·91-11·94) (HER2+), 3·54 (1·52-8·20) (triple-negative), and 2·78 (1·45-5·31) (ER/PR+&HER2-), albeit results were not significant for HER2+ cancers.</p><p><strong>Interpretation: </strong>Our findings indicate that the prognostic scores generated by the response model could identify patient subgroups with relatively poor outcomes under their actual treatments. These preliminary findings may inform future efforts toward personalized NAT regimen selection beyond traditional criteria such as cancer stage and subtype, but should be interpreted cautiously and validated in prospective studies with longer follow-up because these tumors can relapse at a later stage.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103356"},"PeriodicalIF":10.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728682","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":"Artificial intelligence-augmented ultrasound diagnosis of follicular-patterned thyroid neoplasms: a multicenter retrospective study.","authors":"Hui Shen, Shufang Pei, Yue Huang, Suqing Wu, Chifa Zhang, Ting Liang, Dan Yang, Xiaoxiao Feng, Shuyi Liu, Yu Wang, Weihan Cao, Ying Cheng, Hongyan Chen, Qiujie Ni, Fei Wang, Jingjing You, Zhe Jin, Wenle He, Jie Sun, Dexing Yang, Lijuan Liu, Boling Cao, Xiao Zhang, Yingjia Li, Shuixing Zhang, Bin Zhang","doi":"10.1016/j.eclinm.2025.103351","DOIUrl":"10.1016/j.eclinm.2025.103351","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Conventional diagnostic tools, including ultrasound, fine-needle aspiration cytology, and intraoperative frozen section pathology, may fail to reliably distinguish between benign and malignant follicular-patterned thyroid neoplasms (FNs), leading to unnecessary or inadequate surgical interventions. We aimed to develop and validate a deep learning (DL) system for the preoperative diagnosis of FNs using routine ultrasound images, with the goal of improving diagnostic accuracy and reducing unnecessary procedures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this multicenter, retrospective study, we included 3817 patients (2877 [75.4%] female) with a definitive diagnosis of FNs from 11 centers across China. All patients underwent preoperative ultrasound examinations. The dataset comprised 9393 ultrasound images, including thyroid follicular adenoma (n = 1787, 4317 images), follicular carcinoma (n = 446, 1593 images), and follicular variant of papillary thyroid carcinoma (n = 1584, 3483 images) collected between 2012 and 2025. A state-of-the-art OverLoCK (Overview-first-Look-Closely-next ConvNet with Context-Mixing Dynamic Kernels) model was developed on a dataset comprising 2728 patients (6625 images) and validated on an internal cohort (n = 683, 1905 images) and an external cohort (n = 406, 863 images). Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score. Model calibration was evaluated using calibration curves, while clinical usefulness was assessed through decision curve analysis (DCA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;The OverLoCK model exhibited excellent performance in both the internal and external validation sets. In the internal validation cohort, the OverLoCK model achieved an AUC of 0.937 (95% confidence interval [CI]: 0.919-0.954), with accuracy of 90.9% (95% CI: 87.7-92.0), sensitivity of 93.9% (95% CI: 91.5-95.6), specificity of 84.8% (95% CI: 82.6-86.0), PPV of 92.7% (95% CI: 90.7-93.8), NPV of 87.2% (95% CI: 86.0-91.0), and F1 score of 0.911 (95% CI: 0.887-0.932). In the external validation cohort, the model yielded an AUC of 0.853 (95% CI: 0.832-0.876), accuracy of 82.8% (95% CI: 81.7-84.4), sensitivity of 84.5% (95% CI: 82.5-86.2), specificity of 81.1% (95% CI: 79.2-84.5), PPV of 80.4% (95% CI: 79.0-84.0), NPV of 85.1% (95% CI: 83.2-87.7), and F1 score of 0.839 (95% CI: 0.802-0.877). The DL model demonstrates good agreement between the predicted and actual probabilities of malignancy. DCA confirmed that the model was clinically useful.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Our study demonstrates that a DL-based system can provide a noninvasive, accurate, and reliable tool for the preoperative diagnosis of FNs. By improving diagnostic precision, this approach has the potential to optimize clinical decision-making and reduce the burden of overtreatment in patients with FNs. Further","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103351"},"PeriodicalIF":10.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689566","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":"Respiratory infections in pregnancy and early life-association with the development of islet autoimmunity and type 1 diabetes in children: systematic review and meta-analysis of observational studies.","authors":"Claire J Sung, Orlaith M Plowman, Anna J Maxwell, William D Rawlinson, Maria E Craig, Ki Wook Kim","doi":"10.1016/j.eclinm.2025.103324","DOIUrl":"10.1016/j.eclinm.2025.103324","url":null,"abstract":"<p><strong>Background: </strong>Respiratory tract infections (RTIs) in pregnancy and early childhood are potential environmental triggers of islet autoimmunity (IA) and type 1 diabetes (TD). We reviewed the association between gestational and childhood RTIs and the development of IA or T1D in the offspring.</p><p><strong>Methods: </strong>Systematic review and meta-analysis, analysed using random effects models, of observational human studies from Medline and EMBASE, without language restriction, from inception until Jan 6, 2025. The inclusion criteria were cohort, case-control, nested case control or retrospective cohort studies investigating confirmed RTI in childhood or pregnancy by reported history or detection by throat swab before/at IA seroconversion and/or T1D diagnosis in children aged < 18 years. The study is registered with PROSPERO, CRD42020193860.</p><p><strong>Findings: </strong>The systematic review included 26 studies of childhood RTIs involving 12,236,305 participants (14,646 cases, 12,221,659 controls) and four studies of gestational RTIs involving 109,976 participants (979 cases, 108,997 controls). Study design and quality varied, with moderate to high statistical heterogeneity. Meta-analysis of 15 studies demonstrated that childhood RTIs were significantly associated T1D (OR 1.47, 95% CI 1.23-1.75, p < 0.0001) but not significantly associated with IA. Meta-analysis of studies investigating gestational RTIs and T1D found no significant associations and only one of the studies found an association between maternal RTIs in the first trimester based on history and T1D in the offspring (OR 2.31, 95% CI 1.32-4.04, p = 0.002).</p><p><strong>Interpretation: </strong>Our analysis suggests childhood RTIs were significantly associated with risk of T1D, highlighting the need to further investigate the association between childhood RTIs using molecular testing and subsequent risk of IA/T1D.</p><p><strong>Funding: </strong>JDRF, NHMRC.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"85 ","pages":"103324"},"PeriodicalIF":9.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674185","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":"Erratum: Oral human papillomavirus (HPV) prevalence and genotyping among healthy adult populations in the United States and Europe: results from the PROGRESS (PRevalence of Oral hpv infection, a Global aSSessment) study.","authors":"Laia Alemany, Marisa Felsher, Anna R Giuliano, Tim Waterboer, Haitham Mirghani, Hisham Mehanna, Craig Roberts, Ya-Ting Chen, Núria Lara, Mark Lynam, Mayara Torres, Montse Pedrós, Emilio Sanchez, Jacque Spitzer, Bradley Sirak, Beatriz Quirós, Gema Carretero, Sonia Paytubi, Edith Morais, Miquel Angel Pavón","doi":"10.1016/j.eclinm.2025.103335","DOIUrl":"https://doi.org/10.1016/j.eclinm.2025.103335","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.eclinm.2024.103018.].</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"85 ","pages":"103335"},"PeriodicalIF":9.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674166","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":"Predictors of response and enteral autonomy in children with short bowel syndrome treated with teduglutide: a real-life multicentre cohort study.","authors":"Lorenzo Norsa, Arianna Ghirardi, Esther Ramos Boluda, Anat Guz-Mark, Iva Hojsak, Johannes Hilberath, Ilse Juia Broekaert, Rocío González Sacristán, Antonella Lezo, Paula Guerra, Pierre Poinsot, Cecile Lambe, Lorenzo D'Antiga","doi":"10.1016/j.eclinm.2025.103343","DOIUrl":"10.1016/j.eclinm.2025.103343","url":null,"abstract":"<p><strong>Background: </strong>Teduglutide (TED), a glucagon-like peptide 2 analogue licensed for children with short bowel syndrome (SBS), is increasingly used in the attempt to augment intestinal absorption and lower parenteral nutrition (PN) needs. Data from real-life studies on TED efficacy and predictors of response in children with SBS are limited. This study aimed to define pre-treatment and on-treatment predictors of response, in terms of PN reduction and weaning, in TED treated children with SBS.</p><p><strong>Methods: </strong>In this multicenter cohort study, we collected retrospective and prospective data of children with SBS undergoing TED treatment in 7 countries in Europe (Italy, Spain, Croatia, Germany, France, Israel, Portugal). All children with SBS starting TED treatment and not included in clinical trials were eligible. Information on patients' post-surgical anatomy, amount of PN calories and volume required at baseline and at 3, 6 and 12 months after TED start, along with biochemical markers of PN tolerance and complications, were recorded. The main outcome was predicting factors of 1 year response to TED treatment defined as a reduction of ≥20% of PN needs.</p><p><strong>Findings: </strong>Between 01.06.2021 and 31.05.2023, we collected information on 104 children (64 males, 61.5%; 40 females, 38.5%) the median age at enrolment was 6.7 years old (IQR: 3.6-10.4); at 12 months' follow up after TED start 68 children achieved response (cumulative incidence: 70%, 95% CI 61%-79%), whereas complete PN weaning was achieved in 21 children (cumulative incidence: 22%, 95% CI 15%-31%). Multivariable logistic regression analysis showed that predictors of response were longer residual small bowel length (p = 0.027), higher weight Z-score at baseline (p = 0.0061) and normal liver enzymes (p = 0.010). Pre-treatment PN calories <35 kcal/kg/day (p = 0.044) and citrulline ≥14 μmol/L (p = 0.047) predicted complete PN weaning, as well as haemoglobin and citrulline rise in the first 6 months of treatment (p = 0.014 and p = 0.044 respectively).</p><p><strong>Interpretation: </strong>In children with SBS, longer residual small bowel, better nutritional status and absence of liver disease were associated with response to teduglutide. Complete PN weaning was predicted by lower calories needs and higher citrulline at baseline. An increase of haemoglobin and citrulline in the first 6 months of treatment were further predictors of complete PN weaning. Even if limited by the real-life design of the study, these findings may guide a tailored indication for the use of teduglutide in children with short bowel syndrome.</p><p><strong>Funding: </strong>The European Society of Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Networking grant.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"85 ","pages":"103343"},"PeriodicalIF":9.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674184","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}