EClinicalMedicine最新文献

{"title":"Efficacy and safety of liposomal irinotecan plus nimotuzumab in immune checkpoint inhibitor-refractory recurrent or metastatic nasopharyngeal carcinoma: a single-arm, open-label, phase II trial.","authors":"Shuiqing He, Wei-Xin Bei, Nian Lu, Ze-Yu Zhao, Yanfang Ye, Chunyan Chen, Linquan Tang, Liting Liu, Shuhui Lv, Yan-Qun Xiang, Lin Wang","doi":"10.1016/j.eclinm.2026.104170","DOIUrl":"10.1016/j.eclinm.2026.104170","url":null,"abstract":"<p><strong>Background: </strong>Patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) who progress after immune checkpoint inhibitor (ICI) therapy have limited treatment options and poor outcomes. We evaluated the efficacy and safety of liposomal irinotecan plus nimotuzumab in patients with epidermal growth factor receptor (EGFR)-positive, ICI-refractory R/M NPC.</p><p><strong>Methods: </strong>In this single-arm, open-label, phase II trial (NCT06414577) conducted in China, patients with EGFR-positive, ICI-refractory R/M NPC were enrolled between May 27, 2024, and January 9, 2025. Patients received intravenous liposomal irinotecan (70 mg/m²) plus nimotuzumab (400 mg) every 2 weeks for up to eight cycles. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1.</p><p><strong>Findings: </strong>Thirty-six heavily pretreated patients were enrolled, of whom 12 (33.3%) had received three or more prior lines of therapy for advanced disease. In the intention-to-treat population, 13 of 36 patients achieved an objective response (ORR 36.1%; 95% CI 20.8-53.8), and 22 of 36 patients achieved disease control (61.1%). Median progression-free survival was 3.0 months (95% CI, 2.2-4.1), and median duration of response was 2.3 months (95% CI 1.5-3.1). After a median follow-up of 22.0 months, the median overall survival was 14.1 months (95% CI, 8.7-not estimable). Grade 3 or higher treatment-related adverse events occurred in eight of 36 patients (22.2%), and no treatment-related deaths were observed. In a post-hoc exploratory analysis, an early decline of at least 50% in plasma Epstein-Barr virus DNA was associated with a higher ORR.</p><p><strong>Interpretation: </strong>Liposomal irinotecan plus nimotuzumab showed preliminary antitumor activity and manageable safety in heavily pretreated patients with ICI-refractory R/M NPC. However, response durability was limited, and further comparative studies are needed to evaluate its clinical value and identify patients most likely to derive durable benefit.</p><p><strong>Funding: </strong>Supported by grants from the National Natural Science Foundation of China, Science and Technology Program of Guangdong Esophageal Cancer Institute, and China Postdoctoral Science Foundation.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104170"},"PeriodicalIF":12.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954942","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":"Second ipsilateral locoregional recurrence in patients with hormone receptor-positive, HER2-negative breast cancer: a cohort study.","authors":"Monica Milano, Carmine Valenza, Nadia Bianco, Simona Manacorda, Matteo Cavallone, Letizia Matera, Renato Maria Marsicano, Elena Battaiotto, Pier Paolo Maria Berton Giachetti, Edoardo Giordano, Julian David Etessami, Dario Trapani, Simone Schena, Claudia Sangalli, Sabrina Kahler Ribeiro Fontana, Sara Gandini, Paolo Veronesi, Viviana Galimberti, Marco Colleoni, Giuseppe Curigliano, Elisabetta Munzone","doi":"10.1016/j.eclinm.2026.104174","DOIUrl":"10.1016/j.eclinm.2026.104174","url":null,"abstract":"<p><strong>Background: </strong>Evidence regarding outcomes in patients with hormone receptor (HR)-positive/HER2-negative breast cancer (BC) with a second consecutive ipsilateral locoregional recurrence (LRR) remains limited.</p><p><strong>Methods: </strong>Single-center, cohort study including consecutive patients with HR-positive/HER2-negative BC who underwent surgery (study baseline) for a second consecutive, ipsilateral LRR, at the European Institute of Oncology (Milan) from January 2001 to September 2025. Endpoints included invasive breast cancer-free survival (IBCFS) and distant recurrence-free survival (DRFS).</p><p><strong>Findings: </strong>111 patients were included: median age at study baseline was 61 years. The second LRR occurred in the breast in 44% of patients, in locoregional lymph nodes in 23%, on the mastectomy scar or chest wall in 31%. Endocrine-resistant recurrence was observed in 69% of patients. Overall, 14% of patients received adjuvant chemotherapy and 5% a CDK4/6-inhibitor. At a median follow-up of 6.3 years (95% CI: 4.7-7.9), 57 IBCFS events and 40 DRFS events were reported. Median IBCFS was 6.8 years (95% CI: 4.8-7.6) and median DRFS was 9.6 years (95% CI: 6.9-Not Reached [NR]). Median IBCFS was longer in endocrine-sensitive compared to endocrine-resistant LRR (8.6 years [95% CI: 4.6-NR] vs. 5.3 years [95% CI: 4.0-6.9]), and in intraparenchymal LRR (6.8 years [95% CI: 4.8-NR]) compared to nodal (6.4 years [95% CI: 1.4-NR]) or chest wall (5.1 years [95% CI: 4.0-NR]) recurrence.</p><p><strong>Interpretation: </strong>Among patients experiencing a second consecutive LRR, approximately 50% develop a subsequent IBCFS event within 7 years, supporting consideration of treatment intensification, particularly in endocrine-resistant disease or recurrence involving the chest wall or regional lymph nodes.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104174"},"PeriodicalIF":12.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954963","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":"Camera-based respiratory rate monitoring in unmodified neonatal intensive care - a cross-sectional study in a UK hospital.","authors":"Alex Grafton, Lynn Thomson, Kathryn Beardsall, Joan Lasenby","doi":"10.1016/j.eclinm.2026.104175","DOIUrl":"10.1016/j.eclinm.2026.104175","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Camera-based methods have shown potential for respiratory rate measurement in neonatal intensive care. However existing work is tested on short recordings, which do not represent the range of environments present in the neonatal intensive care unit (NICU) or assess challenging conditions such as movement or poor visibility. This study evaluates a fully automatic respiratory rate measurement system over continuous 24-h periods in the unmodified NICU environment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this single-centre cross-sectional study, 20 babies in the NICU in Addenbrooke's Hospital, Cambridge, UK were recorded using a colour + depth camera, each for around 24 h. Recordings took place between 11 July 2022 and 11 November 2025. Inclusion criteria were: pre-term and nursed in closed incubators; no specific exclusion criteria applied. Existing methods were used to automatically locate the baby, and we used a novel clustering method to extract a respiratory signal and detect the patient's breaths. The primary outcome was the measurement of respiratory rate using the camera, assessed by comparison with data from the clinical standard patient monitor, recorded concurrently. Further post-hoc analysis was conducted on clinical and demographic subsets. This trial is registered on clinicaltrials.gov, ID NCT04831242.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;After excluding intervals where the camera or baby was removed from the incubator, 380 h of valid recording from 20 participants remained. During non-intervention periods (338 h, 77.6% of all, 88.7% of valid), we configured the patient monitor signal quality indices to 57.9% valid measurement, a likely overestimate; the camera achieved 57.8% valid measurement with 1.44 breaths/minute agreement (mean error 0.42) averaged over all periods where both camera and monitor had valid data (136 h, 40.4% of non-intervention, 31.4% of all). Covering affects the valid time (63.6% when uncovered, 51.3% when covered), as do intervals where the baby is more active (61.4% when inactive, 53.5% when active). The error and valid time were worse when the monitor respiratory rate was below 35 breaths/minute (31.0% vs 57.8% valid, 1.98 vs 1.44 error) and more so below 25 breaths/minute (25.6% valid, 7.57 error), though data in this range was limited (0.2% of non-intervention) and the patient monitor may be unreliable.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Respiratory rate measurement using cameras has potential for continuous use in the NICU, beyond previously studied short recordings, achieving mean absolute error (MAE) averaged across all data below 2 breaths/minute while providing valid data 57.8% of the time. The relationship between covering/activity and valid measurement time shows the importance of long recordings in the real-world NICU. The MAE and valid time was worse for babies under 1000 g, requiring continuous positive airway pressure, or when the respiratory rate is below 35 breaths/minu","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104175"},"PeriodicalIF":12.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954967","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":"The benchmark illusion: on the curious underestimation of AI and the uncertainty of its creators' gold standards.","authors":"Christian Pohlkamp, Torsten Haferlach","doi":"10.1016/j.eclinm.2026.104184","DOIUrl":"10.1016/j.eclinm.2026.104184","url":null,"abstract":"<p><p>Artificial intelligence (AI) systems have quietly crossed an uncomfortable threshold: on a growing range of diagnostic tasks, they often match, and in some well-defined tasks even exceed, human performance. Evidence from large language models such as Med-PaLM and GPT-4, and deep learning systems in pathology, radiology, and hematology, shows high accuracy and reproducibility, challenging traditional human benchmarks, although still being subject to substantial heterogeneity in the studies cited. Yet most evaluation frameworks continue to treat human consensus on curated, retrospectively labeled datasets as ground truth, despite well-documented record of cognitive bias, interobserver variability, and diagnostic errors in clinical practice. This creates a striking asymmetry: AI is scrutinized against a putative gold standard whose gold content has never been formally tested-a benchmark illusion. Acknowledging AI's own distinctive failure modes and generalizability problems, this Viewpoint argues that such limitations do not justify clinging to an untested reference. It calls for explicit modeling of ground truth uncertainty, outcome-based validation, and, where appropriate, using AI as an additional reference layer for human performance. The relevant benchmark is no longer clinicians alone, but the human-AI ensemble evaluated within real diagnostic ecosystems and against patient-relevant outcomes.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104184"},"PeriodicalIF":12.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954986","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":"The association of ADHD and ADHD medication with adherence to pharmacotherapy for type 2 diabetes: a population-based cohort study from seven countries.","authors":"Yiling Zhou, Honghui Yao, Tian Xie, Malcolm B Gillies, Yanli Zhang-James, Isabell Brikell, Anders Engeland, Le Gao, Birgitte Dige Semark, Theresa Wimberley, Aske Astrup, Zihan Dong, Dina Sarsembayeva, Melissa Vos, Andrew S C Yuen, Søren Dalsgaard, Stephen V Faraone, Kari Klungsøyr, Henrik Larsson, Kenneth K C Man, Ian C K Wong, Helga Zoega, Harold Snieder, Zheng Chang, Catharina A Hartman","doi":"10.1016/j.eclinm.2026.104182","DOIUrl":"10.1016/j.eclinm.2026.104182","url":null,"abstract":"<p><strong>Background: </strong>Attention-deficit/hyperactivity disorder (ADHD) may compromise adherence to pharmacotherapy in adults with type 2 diabetes, but the relationship is unknown. We investigated the association of ADHD and ADHD medication with antidiabetic medication adherence in multinational cohort data.</p><p><strong>Methods: </strong>Using a common analytical protocol and population-based databases from seven countries, we identified adults initiating non-insulin antidiabetic medication between 2010 and 2020. ADHD was identified by diagnosis or ADHD medication use. We used the proportion of days covered (PDC) to measure antidiabetic medication adherence and defined the primary outcome, poor adherence, as PDC <80% over 1-, 2-, and 5-year follow-up periods. Time-to-first-discontinuation was the secondary outcome. Country-specific estimates were obtained using logistic and Cox regression and pooled using random-effects meta-analyses.</p><p><strong>Findings: </strong>Among 3,643,197 individuals included, 1,871,870 (51.4%) were female and 88,339 (2.4%) had ADHD (76,973 [87.1%] received ADHD medication). Overall, ADHD was not associated with poor adherence to antidiabetic medication (1-, 2-, and 5-year pooled odds ratios [OR]: 1.01 [95% CI 0.90-1.14], 1.03 [0.91-1.17], and 1.12 [0.95-1.31]); country-specific estimates ranged from 0.79 to 1.32, 0.80 to 1.35, and 0.80 to 1.47 at 1, 2, and 5 years, respectively. Among males, ADHD was associated with poorer adherence (1.09 [95% CI 1.00-1.20], 1.12 [1.00-1.24], and 1.23 [1.11-1.37] at 1, 2, and 5 years). Similar results were found for discontinuation. Among individuals with ADHD, ADHD medication use was consistently associated with better adherence over 1-, 2-, and 5-year follow-up periods (e.g., 5-year pooled OR 0.45 [0.30-0.67]); associations were directionally consistent across countries.</p><p><strong>Interpretation: </strong>Among adults with type 2 diabetes, ADHD may not necessarily compromise antidiabetic medication adherence when appropriately managed in routine care. ADHD pharmacological treatment may support adherence among adults with comorbid ADHD and type 2 diabetes, although its causal effect requires further evaluation.</p><p><strong>Funding: </strong>EU Horizon 2020 Research and Innovation Programme.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104182"},"PeriodicalIF":12.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929287","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":"1-Year follow-up evaluation of TAK-003 dengue vaccine effectiveness against symptomatic disease and hospitalisation in adolescents during the 2024-2025 outbreak in São Paulo, Brazil: a test-negative case-control study.","authors":"Lisany Krug Mareto, Thiago Sanches Brumatti, Roberto Dias de Oliveira, Patricia Vieira da Silva, Edinéia Ribeiro Dos Santos, Tatiana Lang D'Agostini, Regiane A Cardoso De Paula, Natalie E Dean, Albert I Ko, Derek A T Cummings, Jason R Andrews, Matt D T Hitchings, Otavio Ranzani, Julio Croda","doi":"10.1016/j.eclinm.2026.104181","DOIUrl":"10.1016/j.eclinm.2026.104181","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Dengue is a growing global health threat. Our initial evaluation of the TAK-003 dengue vaccine in adolescents during the 2024 outbreak in São Paulo State, Brazil, showed short-term protection but suggested possible effectiveness waning after 90-days of the first dose, and had limited power to estimate second-dose effectiveness against hospitalisation. We evaluated 1-year vaccine effectiveness against symptomatic, virologically confirmed dengue and dengue hospitalisation in adolescents during 2024-2025, when DENV-1 and DENV-2 predominated in 2024 followed by increasing DENV-3 transmission in 2025.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We did a test-negative case-control study among adolescents aged 10-15 years in São Paulo State between Feb 20, 2024, and Dec 31, 2025. We extracted individual-level information on demographic characteristics, comorbidities, dengue testing, dengue vaccination, hospitalisation, and death during the study period from the national surveillance databases for dengue (SINAN-Dengue; compulsory notification) and the São Paulo State Secretary of Health vaccination registry (Rede Nacional de Dados em Saúde) on Feb 4, 2026. Cases were defined as acute febrile illness episodes with virologically confirmed dengue, as detected by NS1 antigen or RT-PCR testing within 5 days of symptom onset. Controls were test-negative acute febrile illness episodes. Surveillance data were linked to the state vaccination registry. Vaccine effectiveness after one or two TAK-003 doses was estimated with mixed-effects logistic regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;We analysed 166,390 tests: 65,365 from cases and 101,025 from controls. Vaccine effectiveness against symptomatic dengue was 59.2% (95% CI 56.1-62.0) after one dose and 73.1% (69.1-76.6) after two doses. Against dengue hospitalisation, effectiveness was 74.6% (62.7-82.7) after one dose and 87.9% (73.0-94.6) after two doses. One-dose protection against symptomatic disease showed no evidence of waning over 1-year follow-up: effectiveness was 73.8% (64.7-80.6) at 270-364 days and 76.8% (59.3-86.8) at 365 days or more. Two-dose protection remained stable to 1 year (74.6%, 95% CI 59.0-84.2, at 270-365 days). Findings were robust in sensitivity analyses and comparable during increased DENV-3 circulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Our findings show that TAK-003 demonstrated sustained 1-year protection against symptomatic dengue and dengue hospitalisation in adolescents during a large outbreak. Notably, a single dose showed sustained effectiveness without evidence of waning over 1 year, generating an important hypothesis regarding dose reduction that warrants continued long-term observational evaluation. A second dose provided optimal protection, particularly against hospitalisation. These findings reinforce the importance of dengue vaccination as a public health measure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;National Council for Scientific and Technological D","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104181"},"PeriodicalIF":12.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954949","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":"Comparative effectiveness of GLP-1 receptor agonists versus mineralocorticoid receptor antagonists as fourth-line pharmacological therapy in patients with resistant hypertension and overweight or obesity: a retrospective multicenter cohort study in the USA.","authors":"Zhejia Tian, Jonas M Willerding, Kai M Schmidt-Ott, Anette Melk, Bernhard M W Schmidt","doi":"10.1016/j.eclinm.2026.104176","DOIUrl":"10.1016/j.eclinm.2026.104176","url":null,"abstract":"<p><strong>Background: </strong>Mineralocorticoid receptor antagonists (MRAs) are the guideline-recommended therapy for resistant hypertension. Resistant hypertension is particularly common in individuals with overweight or obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) induce substantial weight loss and reduce cardiovascular and renal events, with modest reductions in blood pressure. Whether GLP-1RAs provide benefit as an alternative therapeutic strategy in patients with resistant hypertension and overweight or obesity is unknown. We compared the effectiveness of GLP-1RAs and MRAs as fourth-line pharmacologic therapy in this population.</p><p><strong>Methods: </strong>In this retrospective multicenter cohort study using the TriNetX US Collaborative Network including 67 healthcare organizations, female and male adults with overweight or obesity and resistant hypertension (uncontrolled blood pressure despite ACE-inhibitors/angiotensin receptor blockers, calcium antagonists and diuretics) initiating a fourth-line pharmacological therapy between 01 June 2017 and 31 March 2025 were identified and included. Patients initiating GLP-1RAs (semaglutide or tirzepatide) were compared with those initiating MRAs (spironolactone or eplerenone). The primary outcome was major adverse cardiovascular events (MACE) during 2-year follow-up. Secondary outcomes included all-cause mortality, cardiovascular events, kidney outcomes, and blood pressure changes. Propensity score matching balanced baseline characteristics. Outcomes were analyzed using Kaplan-Meier estimates and Cox proportional hazards models.</p><p><strong>Findings: </strong>Among 213,309 eligible patients, 22,694 initiated GLP-1RAs and 5673 initiated MRAs. After propensity score matching, 4153 patients remained in each group. During a median follow-up of 1.4 years, GLP-1RA therapy was associated with lower risks of MACE (HR 0.63, 95% CI 0.52-0.78), all-cause mortality (HR 0.34, 95% CI 0.21-0.55), cardiovascular events (HR 0.74, 95% CI 0.59-0.92), major adverse kidney events (HR 0.64, 95% CI 0.46-0.88), and acute kidney injury (HR 0.62, 95% CI 0.46-0.83) compared with MRAs. Systolic blood pressure reductions at 12 weeks were similar (-5.7 [95% CI -4.0 to -7.4] mmHg versus -6.3 [95% CI -4.7 to -8.0] mmHg).</p><p><strong>Interpretation: </strong>In our retrospective study, among adults with resistant hypertension and overweight or obesity, GLP-1RA was associated with lower cardiovascular and kidney risk compared with MRAs despite smaller blood pressure reductions. GLP-1RAs may represent a potential alternative or complementary therapeutic option in this population. Prospective studies are needed to determine whether GLP-1RAs should be incorporated into treatment strategies for resistant hypertension in patients with overweight or obesity.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104176"},"PeriodicalIF":12.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896715","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":"Circadian and behavioral timing in MASLD: a systematic review of human observational studies.","authors":"Arunkumar Subramanian, Raja Affendi Raja Ali, Gavin Stewart Dawe, Vetriselvan Subramaniyan","doi":"10.1016/j.eclinm.2026.104187","DOIUrl":"10.1016/j.eclinm.2026.104187","url":null,"abstract":"<p><strong>Background: </strong>Circadian disruption may affect metabolism through altered timing of sleep, activity, light exposure, hormonal rhythms, and food intake. However, its relationship with metabolic dysfunction-associated steatotic liver disease (MASLD), including fibrosis and cirrhosis remains unclear. To evaluate associations between circadian and behavioural timing exposures and MASLD in observational studies.</p><p><strong>Methods: </strong>PubMed, Embase, and Scopus were searched from inception to 14 July 2026. Eligible studies examined naturally occurring timing-related exposures in adults and reported steatosis, fibrosis, cirrhosis, or quantitative liver-fat outcomes. Findings were synthesized narratively because heterogeneity precluded pooling. Risk of bias was assessed using AXIS or the Newcastle-Ottawa Scale, and certainty using an adapted domain-level GRADE approach (PROSPERO Registration number: CRD420261381636).</p><p><strong>Findings: </strong>Twenty-four independent MASLD-related evidence sources were included in the primary synthesis; two additional mixed-aetiology cirrhosis studies were considered contextually. Shift work showed the most consistent associations and most longitudinal evidence. Chronotype was generally associated with disease occurrence but inconsistently with advanced outcomes: intermediate or late chronotype was associated with fibrosis in one clinical cohort, whereas morning chronotype was not independently associated with incident cirrhosis in a prospective cohort. Later sleep timing was associated with prevalent MASLD and, in one NHANES analysis, fibrosis. Evidence for objective rest-activity rhythms, light exposure, meal timing, and melatonin phase remained limited or heterogeneous. Mixed-aetiology cirrhosis studies suggested that advanced liver disease may itself disrupt circadian physiology.</p><p><strong>Interpretation: </strong>Circadian and behavioural timing exposures showed trends associated with MASLD-related outcomes, with the most consistent evidence for shift work. Residual confounding, cross-sectional designs, self-reported exposures, heterogeneous outcomes, and reverse causality preclude causal conclusions. Prospective studies using objective circadian phenotyping and standardized fibrosis outcomes are needed.</p><p><strong>Funding: </strong>This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104187"},"PeriodicalIF":12.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896670","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":"Risks of adverse respiratory outcomes in adults with cancer over the course of survivorship compared with cancer-free individuals: a matched cohort study using linked English electronic health records.","authors":"Kirsty Andresen, Helena Carreira, Harriet Forbes, Liza Bowen, Jennifer K Quint, Elizabeth Williamson, Krishnan Bhaskaran","doi":"10.1016/j.eclinm.2026.104173","DOIUrl":"10.1016/j.eclinm.2026.104173","url":null,"abstract":"<p><strong>Background: </strong>We aimed to compare the risks of developing new chronic respiratory conditions, or exacerbating existing ones in survivors of 20 common cancers vs. cancer-free individuals.</p><p><strong>Methods: </strong>We conducted a population-based matched cohort study using English electronic primary care records, linked to cancer registry, hospital admissions, and death records data from 1999 to 2019. Adults aged ≥ 18 years with incident cancer were matched 1:10 to cancer-free individuals on age, sex and general practice. Outcomes included new-onset and exacerbations of asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and interstitial lung disease (ILD) ascertained from electronic health record (EHR) data throughout follow-up. Relative risks were estimated using Cox models, adjusted for confounders, like smoking. Absolute risks were estimated using adjusted incident rate differences and standardised cumulative incidence curves for new-onset disease and mean cumulative count for exacerbations.</p><p><strong>Findings: </strong>789,254 adults with incident cancer were included. Compared with cancer-free individuals, ILD risk was raised in 18 cancers (adjusted hazard ratio [adjHR] > 5 in CNS, oesophageal and lung cancers, and adjHR > 2 in seven further cancers); raised risks persisted beyond five years after diagnosis in 11 cancers. Elevated risks of developing COPD were observed in 11 cancers (adjHR 4.69 increased risk for lung cancer; other adjHRs 1.08-1.71); for seven of these cancers, raised risks persisted beyond five years. New-onset bronchiectasis risk was increased in oesophageal, lung and haematological cancers while new-onset asthma risk was raised in non-Hodgkin lymphoma only. Exacerbations rates of pre-existing respiratory diseases were raised in survivors of oesophageal, liver, lung, pancreatic, central nervous system, and haematological cancers.</p><p><strong>Interpretation: </strong>Survivors of most types of cancer had substantial and sometimes prolonged raised risk of a range of respiratory conditions. Future research should explore the mechanisms underlying these associations, including the roles of post-cancer tobacco use and specific anti-cancer treatments. Targeted management, smoking cessation, and vaccination may be warranted for those at highest risk.</p><p><strong>Funding: </strong>Medical Research Council and Wellcome trust.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104173"},"PeriodicalIF":12.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896688","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":"Corrigendum to \"Electroacupuncture for knee osteoarthritis: a multicentre randomised controlled trial assessing symptomatic and structural efficacy\".","authors":"Minghui Hang, Yubo Shao, Wang Lu, Xiaoyun Wang, Hao Xu, Shaohua Chen, Xiang Yu, Junjun Zhu, Xianggeng Luo, Honggang Yi, Jiabao Zhang, Yimeng Wang, Shiyong Xue, Shunchao Liu, Zheng Gong, Zhipeng Song, Lianbo Xiao, Zheng Xiang, Shiyan Yan, Ting Zhang, Ruoyu Yao, Tao Wang, Zhanying Tang, Lin Cong, Qiang Li, Haiyin Zhao, Weiwei Meng, Yibin Fan, Rongguang Ao, Bingli Liu, Liyuan Tao, Xiaohua Gu, Li Ding, Tao Wu, Yong Xu, Yongjun Wang, Qianqian Liang","doi":"10.1016/j.eclinm.2026.104161","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.104161","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.eclinm.2026.103982.].</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104161"},"PeriodicalIF":12.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896677","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}