EClinicalMedicine最新文献

{"title":"Pembrolizumab plus gemcitabine and cisplatin for advanced biliary tract cancer: longer-term follow-up from the randomised, double-blind, placebo-controlled, phase 3 KEYNOTE-966 trial.","authors":"Makoto Ueno, Changhoon Yoo, Zhenggang Ren, Junji Furuse, Robin Kate Kelley, Stephen Lam Chan, Julien Edeline, Heinz-Josef Klümpen, Thomas Yau, Chris Verslype, Masato Ozaka, Mohamed Bouattour, Joon Oh Park, Arndt Vogel, Juan W Valle, Liis Starkopf, Usha Malhotra, Abby B Siegel, Shukui Qin, Richard S Finn","doi":"10.1016/j.eclinm.2026.104213","DOIUrl":"10.1016/j.eclinm.2026.104213","url":null,"abstract":"<p><strong>Background: </strong>At the final analysis of KEYNOTE-966 (median follow-up 25·6 months), pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group) versus placebo plus gemcitabine and cisplatin (placebo group) provided a statistically significant, clinically meaningful improvement in overall survival without any new safety signals in participants with advanced biliary tract cancer. We report results from a median study follow-up of 36·6 months (∼3 years).</p><p><strong>Methods: </strong>In the randomised, double-blind, placebo-controlled, phase 3 KEYNOTE-966 trial conducted at 175 medical centres worldwide, eligible participants aged ≥18 years with previously untreated advanced biliary tract cancer were randomly assigned (1:1) to pembrolizumab 200 mg or placebo intravenously every 3 weeks plus gemcitabine 1000 mg/m² and cisplatin 25 mg/m² intravenously on days 1 and 8 of every 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease status, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population (all participants randomly assigned to a treatment). Safety was evaluated in the as-treated population, comprising all participants who received at least one dose of study treatment. As the primary endpoint was met at the final analysis, updated data are reported without p values. This study is registered at ClinicalTrials.gov, NCT04003636.</p><p><strong>Findings: </strong>Between Oct 4, 2019, and June 8, 2021, 1069 participants were randomly assigned to the pembrolizumab group (n = 533) or the placebo group (n = 536). Median follow-up at data cutoff (Nov 14, 2023) was 36·6 months (IQR 32·7-41·4). The hazard ratio for overall survival was 0·86 (95% CI, 0·75-0·98) with pembrolizumab versus placebo; estimated 36-month overall survival rates were 13% (95% CI, 11-17) in the pembrolizumab group and 11% (95% CI, 8-14) in the placebo group. Grade 3 or 4 treatment-related adverse events occurred in 370 (70%) of 529 participants in the pembrolizumab group and 367 (69%) of 534 participants in the placebo group. No new treatment-related deaths occurred since the final analysis.</p><p><strong>Interpretation: </strong>With extended follow-up, the survival benefit of pembrolizumab plus gemcitabine and cisplatin observed at the final analysis persists with approximately 3 years of follow-up, with no new safety signals among participants with previously untreated metastatic or unresectable biliary tract cancer.</p><p><strong>Funding: </strong>Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"100 ","pages":"104213"},"PeriodicalIF":12.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223630","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":"Enterotoxigenic <i>Escherichia coli</i> hyperimmune bovine colostrum for preventing travellers' diarrhoea (TD): a randomised, double-blind, placebo-controlled trial.","authors":"Tahaniyat Lalani, Nathanial K Copeland, Jerry Q Barton, Christina Schofield, Rhonda E Colombo, Tom Troth, Sylviane Defres, Michelle Rizzo-Pelley, Christie A Joya, Michele Cerroni, Huai-Ching Kuo, Ningbo Jian, Tara Griffith, Daniel Burns, Chad K Porter, Joanna Rimmer, David R Tribble","doi":"10.1016/j.eclinm.2026.104249","DOIUrl":"10.1016/j.eclinm.2026.104249","url":null,"abstract":"<p><strong>Background: </strong>Enterotoxigenic <i>Escherichia coli</i> (ETEC) is a leading cause of travellers' diarrhoea (TD). Hyperimmune bovine colostrum (HBC) containing ETEC specific antibodies has shown efficacy in controlled settings, but despite widespread use, real-world efficacy remains uncertain.</p><p><strong>Methods: </strong>In this randomised, double-blind, placebo-controlled superiority trial, US and UK military personnel and adult civilians (aged 18-70 years) travelling to TD-risk regions were randomised (1:1) to receive ETEC HBC (600 mg twice daily) or placebo, starting 2 days before arrival and continuing for 10-20 days while in the risk area. The primary outcome was TD, defined by standardised criteria. Stool smears collected during diarrhoeal episodes and at the end-of-prophylaxis were tested by PCR for pathogen attribution. ETEC-attributable TD was assessed as a secondary outcome. This trial is registered with ClinicalTrials.gov, NCT04605783 and is complete.</p><p><strong>Findings: </strong>Between June 2, 2022, and April 29, 2025, 975 participants were enrolled and 850 were randomised to ETEC HBC (n = 425) or placebo (n = 425). Of these, 317 ETEC HBC and 323 placebo recipients were included in the primary efficacy analysis. TD occurred in 22.7% of ETEC HBC and 26.3% of placebo recipients (relative protective efficacy [PE] 13.7 [95% CI -13.4 to 34.31]), below the protocol-specified efficacy threshold of ≥35%. ETEC accounted for 17% of attributable TD cases, with frequent multi-organism detections. The difference in ETEC attributable TD between the groups was not statistically significant (12.1 vs. 21.5%; PE: 43.8 [-28.5 to 75.4]). Adverse events were rare and mild (ETEC HBC 2/320 vs. placebo 2/325). Both events in the ETEC HBC group (frequent urination, hives) resolved spontaneously.</p><p><strong>Interpretation: </strong>ETEC HBC did not significantly reduce overall TD risk, with interpretation of ETEC-specific efficacy constrained by limited power. Further research is warranted to determine whether broader ETEC antigenic coverage or multi-pathogen approaches can overcome the pathogen diversity and polymicrobial infections observed in field settings.</p><p><strong>Funding: </strong>Defense Health Agency.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"100 ","pages":"104249"},"PeriodicalIF":12.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215223","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":"Authors' reply to \"Sex and weighting in abbreviated DASI-based perioperative risk prediction\".","authors":"Duminda N Wijeysundera, Keying Xu, Daniel I McIsaac","doi":"10.1016/j.eclinm.2026.104254","DOIUrl":"10.1016/j.eclinm.2026.104254","url":null,"abstract":"","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"100 ","pages":"104254"},"PeriodicalIF":12.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215158","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":"Sex and weighting in abbreviated DASI-based perioperative risk prediction.","authors":"Kwok M Ho, Bernhard Riedel, Jonas Alfitian, Robert Schier, Hilmy Ismail","doi":"10.1016/j.eclinm.2026.104253","DOIUrl":"10.1016/j.eclinm.2026.104253","url":null,"abstract":"","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"100 ","pages":"104253"},"PeriodicalIF":12.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215161","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 and clinical course of pelvic pain among transmasculine individuals on gender-affirming testosterone: a systematic review and meta-analysis.","authors":"Susanna Weidlinger, Angela Niggli, Mick van Trotsenburg, Katharina Feil, Constanze Weidlinger, Angela Vidal, Marietta Gulz, Janna Pape, Jessica Laue, Brigitte Leeners, Michael von Wolff, Tanya Karrer, Karin Camastral-Urech","doi":"10.1016/j.eclinm.2026.104233","DOIUrl":"10.1016/j.eclinm.2026.104233","url":null,"abstract":"<p><strong>Background: </strong>Pelvic pain is increasingly recognised among transmasculine individuals receiving gender-affirming testosterone therapy, yet no systematic synthesis of prevalence or clinical course exists.</p><p><strong>Methods: </strong>We conducted the first systematic review and meta-analysis of pelvic pain in transgender individuals. We searched MEDLINE, Embase, Scopus, and CENTRAL from January 2013 to June 2026. Studies reporting prevalence or clinical course of pelvic pain in transmasculine individuals with or without testosterone therapy were included. Methodological quality was assessed using Joanna Briggs Institute checklists. Pooled prevalence estimates were calculated using random-effects models. PROSPERO registration: CRD420261278643.</p><p><strong>Findings: </strong>Eleven studies encompassing 4176 transmasculine individuals were included, of whom 2891 received testosterone therapy. Among those receiving testosterone, the pooled prevalence of pelvic pain was 39% (95% CI 23-55%), significantly higher than in cisgender women (5-25%). Prevalence was higher in surgical cohorts (50%, 95% CI 12-88%) than in non-surgical populations (28%, 95% CI 13-46%). New-onset pelvic pain was reported in 31% (95% CI 5-65%) of previously asymptomatic individuals after testosterone initiation. Critically, among individuals with preexisting pain, 72% (95% CI 62-81%) reported persistence, while only 26% (95% CI 18-34%) reported improvement or remission after testosterone initiation.</p><p><strong>Interpretation: </strong>Pelvic pain is common among transmasculine individuals and frequently persists despite testosterone therapy. These findings challenge the widespread assumption that androgenic hormonal transition is protective against pelvic pain and highlight the urgent need for proactive assessment and gender-affirming management in this population. Prospective studies with standardised pain assessment and investigation of hormonal, tissue-level, and psychosocial mechanisms are needed to develop evidence-based interventions.</p><p><strong>Funding: </strong>No funding was received.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"100 ","pages":"104233"},"PeriodicalIF":12.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215226","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":"Cost-effectiveness of adding enzalutamide vs standard non-steroidal antiandrogen drugs for patients with metastatic hormone-sensitive prostate cancer undergoing standard first-line therapy: a within-trial, secondary end-point analysis of the ENZAMET phase 3, international randomized trial (ANZUP 1304).","authors":"Chi Kin Law, Martin R Stockler, Andrew J Martin, Ian D Davis, Christopher J Sweeney, Rachael L Morton","doi":"10.1016/j.eclinm.2026.104207","DOIUrl":"10.1016/j.eclinm.2026.104207","url":null,"abstract":"<p><strong>Background: </strong>The ENZAMET randomized trial demonstrated adding enzalutamide to testosterone suppression, compared with a less potent comparator, significantly improved overall and progression-free survival in men with metastatic hormone-sensitive prostate cancer (mHSPC). This study evaluated cost-effectiveness of adding enzalutamide to standard therapy over 60 months.</p><p><strong>Methods: </strong>A within-trial cost-effectiveness analysis was conducted from an Australian health system perspective using prospectively collected, observed data from ENZAMET open-label, phase 3 RCT. This study is registered with ClinicalTrials.gov, NCT02446405, ANZCTR, ACTRN12614000110684, and EudraCT, 2014-003190-42. The analysis was conducted utilizing a data cut-off date of January 19, 2022, with a median follow-up of 68 months. Information on disease status, healthcare utilization, and health-related quality of life were extracted from trial records, linked Medicare claims and patient questionnaires. Costs were calculated in 2023 Australian dollars. EQ-5D-5L scores were converted to health utilities using a validated algorithm. Quality-adjusted life years (QALYs) were estimated by multiplying mean health utility with corresponding life-years accumulated. Deterministic and probabilistic sensitivity analyses examined the effect of varying unit price of study drugs, per diem rates of hospital stays, benefits paid from Medicare claims, and health utility values on robustness of results. Data were assessed for missingness and imputation applied where relevant.</p><p><strong>Findings: </strong>Enzalutamide was associated with an additional AUD$127,262 per patient in healthcare costs, 0.24 life-years and 0.15 QALYs gained in the first 5 years, compared with non-steroidal antiandrogen therapy. The incremental cost-effectiveness ratio, (ICER) was AUD$543,880 per life-year gained and AUD$835,580 per QALY gained. Results were sensitive to the cost of study drug, with a purchase price of AUD$6.73 per tablet yielding an ICER that met the willingness-to-pay threshold of AUD$50,000 per QALY gained. Of note, hospitalizations were slightly higher in the enzalutamide group; as was use of musculoskeletal medicines, the latter indicating falls and fractures.</p><p><strong>Interpretation: </strong>Although Enzalutamide improves quality-adjusted survival for men with mHSPC, it is unlikely to be cost-effective. Long-term bone health management in survivors is an important clinical consideration.</p><p><strong>Funding: </strong>Astellas Pharma and Australian National Health and Medical Research Council.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"100 ","pages":"104207"},"PeriodicalIF":12.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215195","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 cross-sectional global policy analysis of the human gap in 156 national cancer strategy plans.","authors":"Emily Lau, Gilla K Shapiro, Gary Rodin, Richard Sullivan, Nirmala Bhoo-Pathy, Karla Unger-Saldaña, Dario Trapani, Naveen Salins, Mac Skelton, Madeline Li","doi":"10.1016/j.eclinm.2026.104244","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.104244","url":null,"abstract":"<p><strong>Background: </strong>National Cancer Strategies (NCS), including National Cancer Control Plans (NCCPs) and Non-Communicable Disease Plans (NCDPs), shape priorities for cancer systems. Yet, little is known about whether they address human-centred care, including psychosocial support, equity, financial protection, and palliative care. We aimed to (1) assess the extent to which NCS include human-centred care themes relevant to sociocultural factors, systems of care, medical education, economic protection, mental health, and palliative care, and (2) compare inclusion across lower- and higher-income settings.</p><p><strong>Methods: </strong>The International Cancer Control Partnership, an initiative developed under the Union for International Cancer Control (UICC), maintains a database of NCS to facilitate cancer planning and policy development worldwide. Using the 2023 UICC global review questionnaire dataset, this secondary analysis examined 20 questionnaire items across 98 NCCPs and 58 NCDPs from 156 countries. Items were grouped into six themes relevant to human-centred care and analyzed by country income level.</p><p><strong>Findings: </strong>Only 12% of NCCPs identified people living with cancer as stakeholders. Most countries included strategies addressing palliative care beyond pain management (84%), and 72% included strategies to support families or caregivers of cancer patients. In contrast, few countries addressed social determinants of health (28%), cancer-related inequities (28%), protection against catastrophic expenditure (14%), or referenced essential medicines for psychological distress (3%). Human-centred care themes were less frequently addressed in lower-income settings compared with higher-income settings (32% vs. 44%).</p><p><strong>Interpretation: </strong>Themes of human-centred care are infrequently included in NCS, particularly in lower-income countries. Global attention to these themes is needed to advance more equitable, human-centred cancer care worldwide.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"100 ","pages":"104244"},"PeriodicalIF":12.8,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180091","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":"High-dose vitamin D₃ supplementation in the prevention of viral-induced asthma in high-morbidity preschoolers (DIVA): a randomised controlled trial in Canada.","authors":"Francine Monique Ducharme, Sze Man Tse, Patrick Daigneault, Connie Lee Yang, Dhenuka Radhakrishnan, Reza Alizadehfar, Marc-André Turcot, Chantal Lemire, Breanna Ashley Chen, Lucy Perrem, Geneviève Mailhot, Nathalie Alos, Anna Smyrnova, Mi-Suk Kang Dufour, Miguel Caubet Fernandez, Megan Elizabeth Jensen, John Howard White, Mohsen Sadatsafavi, Ali Khamessan, Benoît Mâsse","doi":"10.1016/j.eclinm.2026.104216","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.104216","url":null,"abstract":"<p><strong>Background: </strong>Systematic reviews have suggested a beneficial effect of vitamin D supplementation in reducing asthma exacerbations and respiratory infections, with an underrepresentation of individuals with severe asthma and preschoolers. We aimed to examine the efficacy and safety of high-dose vitamin D supplementation for reducing severe exacerbations in preschool-aged children with viral-induced, high-morbidity, and asthma.</p><p><strong>Methods: </strong>In this randomised, placebo-controlled, parallel-group, triple-blind, multicentre trial, children aged 1-5 years with prior viral-induced exacerbations requiring oral corticosteroids (OCS) were enrolled across nine paediatric asthma centres in Canada. Participants were randomly assigned to receive either two oral boluses of 100,000 IU (3·5 months apart) with daily 400 IU vitamin D3, or placebo boluses and daily placebo, over 7 months. The primary outcome was the rate of exacerbations requiring rescue OCS during the 7-month follow-up, analysed by a negative binomial regression model. Secondary outcomes included laboratory-confirmed respiratory infections, health care utilisation, duration and severity of exacerbations, and safety. This trial was prospectively registered with ClinicalTrials.gov (NCT03365687).</p><p><strong>Findings: </strong>Between Sept 18, 2018, and April 22, 2024, 1072 children were screened. Due to pandemic-related recruitment constraints, the trial enrolled 323 children, representing 37% of the planned sample size of 865 children. Participants had a mean age of 2·8 years (65% male) with a median of 2 (interquartile range: 1-3) oral corticosteroid courses in the prior year; at baseline, 48% had baseline serum 25-hydroxyvitamin D (25(OH)D) ≥75 nmol/L and 90% received GINA 2024 Step ≥3 therapy. Compared to placebo, there was no significant group difference in the rate of rescue OCS per child (0·67 ± 0·94 vs. 0·71 ± 1·02, incidence rate ratio [IRR] 0·95; 95% CI 0·70-1·30), laboratory-confirmed infections (1·73 ± 1·71 vs. 1·76 ± 1·55, IRR 0·99; 0·82-1·21), acute-care visits, duration and/or severity of exacerbations, and treatment-emergent or serious adverse events adverse events. The intervention was associated with a rapid and sustained rise in 25(OH)D.</p><p><strong>Interpretation: </strong>In preschoolers with high-morbidity, viral-induced asthma, vitamin D3 supplementation did not significantly reduce severe exacerbation or respiratory viral infection rates, compared to placebo. No safety concerns were observed. With fewer participants than planned, the precision of estimates is limited and the results are inconclusive, thus deserve further exploration.</p><p><strong>Funding: </strong>Canadian Institutes of Health Research.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"100 ","pages":"104216"},"PeriodicalIF":12.8,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179117","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":"MGUS in Black individuals in Soweto, South Africa screened by mass spectrometry: results of the PROMISE South Africa study.","authors":"David J Lee, Wenlong C Chen, Luca Bertamini, Habib El-Khoury, Sabine Allam, Grace Fleming, Jean-Baptiste Alberge, Jacqueline Perry, Maya I Davis, Elizabeth Lightbody, Lindokuhle N Goqwana, Vinitha Philip, Audrey Pentz BRad, Thulisile Hlubi Dip Tchg, Robert Redd, Dhananjay Sakrikar, David Barnidge, Mark C Perkins, Stephen Harding, Julia Colchie, Elizabeth W Karlson, Timothy R Rebbeck, Gad Getz, Maureen Joffe, Irene M Ghobrial, Catherine R Marinac","doi":"10.1016/j.eclinm.2026.104208","DOIUrl":"10.1016/j.eclinm.2026.104208","url":null,"abstract":"<p><strong>Background: </strong>Only few studies have screened for monoclonal gammopathy of undetermined significance (MGUS) among Black Africans in sub-Saharan Africa, with mixed results.</p><p><strong>Methods: </strong>In this cross-sectional study, we enrolled 2004 Black Africans aged 40-75 years from Soweto, South Africa, from January 2021 to August 2023. Participants completed an interview-guided exposure survey, underwent height and weight measurements, and provided blood samples that were screened for MGUS by matrix-assisted laser desorption ionisation-time of flight mass spectrometry. The primary outcome was the prevalence of MGUS, assessed from blood samples collected at the participants' single study visit. Prevalence was compared to those of high-risk United States (US)-based cohorts screened by the same method. Multivariable logistic regression models evaluated associations between exposures and MGUS.</p><p><strong>Findings: </strong>Prevalences of heavy-chain and light-chain MGUS among Black Africans were 12% and 3%. MGUS prevalence among Black Africans were similar to or higher than those of high-risk populations in the US. In multivariable modelling within the South Africa cohort, human immunodeficiency virus (HIV) was associated with MGUS (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.27-2.21; p < 0.001). Smoking was associated with MGUS (<20 pack-years vs never smoking: OR, 1.55; 95% CI, 1.14-2.12; p = 0.01 and ≥20 pack-years vs never smoking: OR, 1.76; 95% CI, 1.21-2.56; p = 0.003). Body mass index (BMI) of ≥30 kg/m² (vs normal BMI) was inversely associated with MGUS (OR, 0.59; 95% CI, 0.40-0.85; p = 0.01), as was high physical activity (≥52.5 vs <10.5 metabolic equivalent of task-hours/week: OR, 0.43; 95% CI, 0.19-0.96; p = 0.04).</p><p><strong>Interpretation: </strong>Results suggest Black South Africans represent a high-risk population with an increased likelihood of having MGUS. HIV, smoking, and physical activity may contribute to prevalence patterns. Prospective studies are needed to further elucidate the role of these risk factors in MGUS development and to identify strategies for early detection, risk stratification, and prevention.</p><p><strong>Funding: </strong>Stand Up To Cancer Dream Team, Multiple Myeloma Research Foundation, and National Institutes of Health.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"100 ","pages":"104208"},"PeriodicalIF":12.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179038","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":"Gestational age references and trajectory of fetal haemoglobin in relation to outcome in neonates born before 30 weeks of gestation: a single-centre retrospective cohort study in The Netherlands.","authors":"Jip H van Daelen, Norani H Gangaram-Panday, Elise J Huisman, H Rob Taal, Thomas R L Klei, Enrico Lopriore, Irwin K M Reiss, Andrei N Tintu, Pauline M Snijder","doi":"10.1016/j.eclinm.2026.104256","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.104256","url":null,"abstract":"<p><strong>Background: </strong>Fetal haemoglobin (HbF) has a high oxygen affinity and predominates during fetal life. After birth, HbF is progressively replaced by adult haemoglobin (HbA). In preterm neonates, transfusion with HbA-containing red blood cells (RBCs) may accelerate this transition, increasing tissue oxygen exposure and oxidative stress, which have been associated with retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. We aimed to establish gestational age (GA)-specific reference values and examine postnatal HbF trajectories in relation to transfusion exposure and outcomes, focusing on neonates born before 30 weeks' gestation.</p><p><strong>Methods: </strong>In this single-centre retrospective cohort study, 856 neonates with HbF measurements (24-42 weeks' gestation) admitted to the ErasmusMC NICU, Rotterdam, the Netherlands (1 February 2020-1 February 2024) were included. GA-specific HbF reference values were derived from day 0 samples. Longitudinal HbF trajectories during NICU admission were analysed in 458 neonates born before 30 weeks' gestation using 9461 blood gas samples. Linear mixed-effects models assessed associations between HbF decline, transfusion exposure, and prematurity-related outcomes.</p><p><strong>Findings: </strong>HbF at birth remained high until approximately 35 weeks' gestation (median ≥0.85) and declined towards term. In neonates born before 30 weeks' gestation, HbF declined during the first postnatal weeks, with the steepest decline seen in babies born at 24-25 weeks' gestation. Neonates who received RBC transfusions showed a steeper HbF decline than those who did not (p < 0.001), as did neonates with prematurity-related outcomes compared with those without major morbidity or mortality (p < 0.001).</p><p><strong>Interpretation: </strong>RBC transfusions accelerate HbF decline in neonates born before 30 weeks' gestation. Its association with prematurity-related morbidity supports evaluation of HbF-preserving transfusion strategies. Future studies should incorporate the interval and frequency of successive transfusions through time-varying cumulative transfusion exposure or analyses centred on individual transfusion events to further refine the temporal dynamics of HbF decline and recovery. These studies should ultimately evaluate the optimal interval and frequency of transfusions and whether HbF-preserving transfusion strategies improve clinical outcomes in extremely preterm neonates.</p><p><strong>Funding: </strong>No funding was received for this work.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"100 ","pages":"104256"},"PeriodicalIF":12.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179095","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}