EClinicalMedicine最新文献

{"title":"Correction of meta-analysis after retraction of article on the effects of anti-androgens in polycystic ovary syndrome.","authors":"Simon Alesi, Maria Forslund, Johanna Melin, Daniela Romualdi, Alexia Peña, Chau Thien Tay, Selma Feldman Witchel, Helena Teede, Aya Mousa","doi":"10.1016/j.eclinm.2024.103009","DOIUrl":"https://doi.org/10.1016/j.eclinm.2024.103009","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.eclinm.2023.102162.].</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"103009"},"PeriodicalIF":9.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930978","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":"Durvalumab and tremelimumab in patients with advanced rare cancer: a multi-centre, non-blinded, open-label phase II basket trial.","authors":"Abha A Gupta, Anna Tinker, Derek Jonker, Rahma Jamal, Hal Hirte, Eric W Winquist, Quincy Chu, Christian Kollmannsberger, Ralph Wong, Thierry Alcindor, Torsten O Nielsen, Ming Tsao, Tricia R Cottrell, Diane Provencher, John Hilton, Monika K Krzyżanowska, Christine Elser, Sebastien Hotte, Joana Sederias, Siwei Zhang, Wei Tu, Janet Dancey","doi":"10.1016/j.eclinm.2024.102991","DOIUrl":"10.1016/j.eclinm.2024.102991","url":null,"abstract":"<p><strong>Background: </strong>Dual inhibition of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) has been shown to be an effective treatment strategy in many cancers. We sought to determine the objective response rate of combination durvalumab (D) plus tremelimumab (TM) in parallel cohorts of patients with carefully selected rare cancer types in which these agents had not previously been evaluated in phase II trials and for which there was clinical or biological rationale for dual immune checkpoint inhibitor therapy to be active.</p><p><strong>Methods: </strong>We designed a multi-centre, non-blinded, open-label phase II basket trial with each of the following 8 rare cancers considered a separate phase II trial: salivary carcinoma, carcinoma of unknown primary (CUP) with tumour infiltrating lymphocytes and/or expressing PD-L1, mucosal melanoma, acral melanoma, osteosarcoma, undifferentiated pleomorphic sarcoma, clear cell carcinoma of the ovary (CCCO) or squamous cell carcinoma of the anal canal (SCCA). The primary objective was to evaluate the response rate of the combination of D and TM, and the secondary objectives were to evaluate the tolerability and safety of D and TM combination. Eligible patients had advanced, metastatic or recurrent, or unresectable cancer with no known life-prolonging treatment option, age ≥16 years, ECOG performance status 0 or 1. Patients received D (1500 mg IV) + TM (75 mg IV) on Day 1 q4 weeks for 4 cycles followed by D q4 weeks until disease progression. This trial is registered with ClinicalTrials.gov, NCT02879162.</p><p><strong>Findings: </strong>From December 14th, 2016, to August 14, 2019, 140 patients enrolled into seven cohorts. The rare melanoma cohorts were closed due to lack of accrual. Of the 140 patients enrolled, 138 were eligible, 138 were evaluable for toxicity and 128 (91%) were evaluable for response. Durable responses were noted in all cohorts except for osteosarcoma. The overall response rate for eligible patients was 16% (95% CI: 10-23%). The response rates in each cancer cohort were undifferentiated pleomorphic sarcoma 15% (n = 3/20; 95% CI 3-38%), salivary carcinoma 20% (n = 4/20; 95% CI: 6-44%), CUP 17% (n = 3/18; 95% CI 4-41%), SCCA 10% (n = 2/20; 95% CI 12-32%) and CCCO 21% (n = 8/39; 95% CI 9-37%). Grade 3/4 adverse events were rare, where 4 patients experienced grade 4 related events and39 patients experienced grade 3 events.</p><p><strong>Interpretation: </strong>Durvalumab + tremelimumab treatment resulted in meaningful responses in salivary carcinoma and CCCO and deserves further exploration in front-line studies.</p><p><strong>Funding: </strong>AstraZeneca and Canadian Cancer Society.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102991"},"PeriodicalIF":9.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906719","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":"Life course socioeconomic position and care dependency in later life: a longitudinal multicohort study from 17 countries.","authors":"Ting Pan, Chenshuang Li, Ying Zhou","doi":"10.1016/j.eclinm.2024.102994","DOIUrl":"10.1016/j.eclinm.2024.102994","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Care dependency, inability to perform basic daily tasks without assistance due to functional impairment, increases substantially with accelerated population ageing and becomes a pressing public health concern worldwide. Socioeconomic disadvantage has been shown to be associated with elevated risks of care dependency, but how risks are modified by changes in socioeconomic position remains unclear. From a life course perspective, we investigated the association between socioeconomic mobility across the lifespan and care dependency in later life.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this longitudinal multicohort study, we pooled data collected between 2000 and 2019 from six prospective cohort studies across 17 countries from the Program on Global Ageing, Health, and Policy. Socioeconomic status (SES) at three different life stages was assessed based on parental education in childhood, participants' education in early adulthood, and non-housing wealth in middle-late adulthood. Care dependency was measured using activities of daily living (ADLs) and instrumental activities of daily living (IADLs) following WHO recommendations. Ordinal logistic mixed-effect models were applied to investigate associations between socioeconomic inequalities and their mobility across the life course with later-life care dependency. Furthermore, to investigate contributors to inequalities in care dependency, we applied the difference method to estimate the proportion of these inequalities explained by potential risk factors, and quantified the health and economic benefits of targeted interventions using population attributable fractions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;A total of 103,282 individuals were involved in this study, with an average baseline age of 63.29 (SD 10.70) years and a mean follow-up of 8.75 (SD 0.02) years. Low SES at any stage of life was associated with elevated probability, increased severity, and accelerated deterioration of care dependency in later life, with women being particularly vulnerable. For the probability of IADL dependency, socioeconomic differences by parental education persisted and were greatest at ages 75-80 years (18.10%, 95% CI 14.25%-21.95% for women; 10.23%, 5.82%-14.64% for men). Considering the severity of dependency, differences in low ADL dependency reversed in advanced old age, while differences in high ADL dependency widened consistently with age. Differences in high ADL dependency between high and low childhood SES groups increased from 0.66% (0.64%-0.67%) at age 50 to 15.79% (12.19%-19.39%) at age 100. Compared with a stable high SES throughout life, all other SES mobility trajectories were associated with elevated risks of both IADL and ADL dependency. Individuals who experienced a severe SES decline-high in childhood but low in adulthood-showed a more than ten times higher risk (IADL: OR 18.26, 95% CI 12.45-26.79; ADL: 11.95, 8.47-16.88). A lower risk was observed for those who moved from ","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102994"},"PeriodicalIF":9.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906752","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":"Effectiveness of the BNT162b2 XBB.1.5-adapted vaccine against COVID-19 hospitalization related to the JN.1 variant in Europe: a test-negative case-control study using the id.DRIVE platform.","authors":"Jennifer L Nguyen, Marianna Mitratza, Hannah R Volkman, Leonie de Munter, Thao Mai Phuong Tran, Catia Marques, Mustapha Mustapha, Srinivas Valluri, Jingyan Yang, Andrés Antón, Irma Casas, Eduardo Conde-Sousa, Laura Drikite, Beate Grüner, Giancarlo Icardi, Gerrit Luit Ten Kate, Charlotte Martin, Ainara Mira-Iglesias, Alejandro Orrico-Sánchez, Susana Otero-Romero, Gernot Rohde, Luis Jodar, John M McLaughlin, Kaatje Bollaerts","doi":"10.1016/j.eclinm.2024.102995","DOIUrl":"10.1016/j.eclinm.2024.102995","url":null,"abstract":"<p><strong>Background: </strong>Prior studies have reported lower effectiveness of XBB.1.5-adapted vaccines against hospitalization related to the Omicron JN.1 variant than the XBB variant. This study evaluated the effectiveness and durability of the BNT162b2 XBB.1.5-adapted vaccine against JN.1-related hospitalization during the 2023-2024 season in Europe.</p><p><strong>Methods: </strong>A test-negative case-control study was carried out in adults (≥18 y) hospitalized between 2 October 2023 and 2 April 2024 with severe acute respiratory infection (SARI) within the id.DRIVE partnership. This study included nine sites across Belgium, Germany, Italy, and Spain. Cases had a laboratory-confirmed JN.1 infection or a positive SARS-CoV-2 test with symptom onset during JN.1 predominance; controls had a negative SARS-CoV-2 test and symptom onset during JN.1 predominance. The primary objective was to estimate BNT162b2 XBB.1.5-adapted vaccine effectiveness (VE) against COVID-19 hospitalization. One case was matched with up to four controls, according to symptom onset date and site. Multivariable analyses were adjusted for symptom onset date, age, sex, and number of chronic conditions.</p><p><strong>Findings: </strong>Among 308 test-positive cases and 1117 test-negative controls, BNT162b2 XBB.1.5-adapted VE against hospitalization compared to no vaccination this season was 53.8% (95% CI 38.4-65.4) after a median of 63 days following vaccination. Protection was sustained through five months; VE was 52.2% (95% CI 41.3-61.1) 2 to <4 weeks after vaccination, 48.9% (95% CI 17.9-68.2) at 4 to <8 weeks, and ranged from 54.6% to 59.5% at 4-week intervals from 8 to <22 weeks.</p><p><strong>Interpretation: </strong>BNT162b2 XBB.1.5-adapted vaccine provided protection against JN.1-related hospitalization, regardless of prior vaccination history, with no evidence of waning through five months. These data support yearly vaccination against COVID-19 to prevent severe illness during the respiratory virus season.</p><p><strong>Funding: </strong>Pfizer.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102995"},"PeriodicalIF":9.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893013","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":"Acceptance and safety of the RSV-preventive treatment of newborns with nirsevimab in the maternity department: a prospective longitudinal cohort study in France.","authors":"Charlotte Ocana de Sentuary, Clara Testard, Marion Lagrée, Maxime Leroy, Lisa Gasnier, Alicia Enes-Dias, Constance Leruste, Diariatou Diallo, Michael Génin, Thameur Rakza, François Dubos","doi":"10.1016/j.eclinm.2024.102986","DOIUrl":"10.1016/j.eclinm.2024.102986","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the acceptance and safety of the treatment of newborns with nirsevimab (a long-acting monoclonal antibody designed to prevent respiratory syncytial virus infections) during the first season of implementation.</p><p><strong>Methods: </strong>A longitudinal, prospective, single-centre cohort study was conducted from September 18th, 2023, to January 23rd, 2024 at Lille University Hospital (Lille, France). All newborns admitted to the hospital's maternity department during the study period and whose parents agreed to participate in the study were included. Parents were asked to state whether or not they agreed for their infant to receive nirsevimab. The occurrence of adverse events (AEs) 2 h after nirsevimab treatment and 7, 14 and 30 days after discharge was documented by the mother. The primary endpoint was the nirsevimab treatment acceptance rate. The secondary endpoints were the variables associated with the acceptance of nirsevimab, the reasons for accepting or refusing nirsevimab, and the treatment's real-life safety, relative to a non-treated control group of newborns.</p><p><strong>Findings: </strong>Of the 1730 infants born in the hospital during the study period, 477 met all the inclusion criteria and were enrolled. The nirsevimab acceptance rate [95% confidence interval] was 91.6% [89.1%-94.2%]. In a multivariable analysis, the mother's age, lower parity and having a partner in work were significantly associated with nirsevimab acceptance. The most common reason for accepting treatment was \"to protect my baby\", and the most common reason for refusing treatment was the lack of long-term data on nirsevimab. The nirsevimab and control groups did not differ significantly in terms of the types and frequencies of AEs. At least one serious AE was reported for 9.4% of the infants in the nirsevimab group and for 10.3% in the control group. None of the serious AEs were considered to be related to nirsevimab treatment.</p><p><strong>Interpretation: </strong>The nirsevimab acceptance rate for newborns in the maternity unit was high during the first season of implementation. The safety profile was very good, with no significant differences between the nirsevimab group and the control group.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102986"},"PeriodicalIF":9.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893009","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":"Global, regional, and national burdens of heart failure in adolescents and young adults aged 10-24 years from 1990 to 2021: an analysis of data from the Global Burden of Disease Study 2021.","authors":"Chengzhi Yang, Yuhe Jia, Changlin Zhang, Zening Jin, Yue Ma, Xuanye Bi, Aiju Tian","doi":"10.1016/j.eclinm.2024.102998","DOIUrl":"10.1016/j.eclinm.2024.102998","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Prior studies suggest prevalence of heart failure (HF) has remained steady or progressively decreased over past 30 years in the general population. Whether this favourable trend occurred in adolescents and young adults aged 10-24 years has yet to be elucidated. We aim to identify the trends in the burden of HF in this young population from 1990 to 2021 to inform areas for targeted intervention and prevention efforts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We analyzed data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. The case number and rates per 100,000 population of prevalence and years lived with disability (YLDs) of HF at the global, regional, and national level in the population aged 10-24 years from 1990 to 2021 were reported. In addition, the HF trends by age, sex, and socio-demographic index (SDI) were analyzed. Furthermore, we calculated the average annual percentage changes (AAPC) and identified the year with the most pronounced changes in the trends with the joinpoint regression analysis. In detail, we divided the study population into three age groups: 10-14 years old, 15-19 years old, and 20-24 years old. We also employed the Bayesian age-period-cohort models (BAPC) to predict the future burden of HF up to 2030.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Globally, the prevalence and YLDs rates of HF among adolescents and young adults in 2021 were 148.1 (95% uncertainty interval [UI]: 118.8-185.7) and 14.4 (9.2-21.2) per 100 000 population, increased from 125.5 (100.0-157.7) and 12.2 (7.8-17.8) in 1990 respectively. Noticeable changes in HF prevalence were found in 1994, 2001, 2004, 2010, and 2018. Regionally, East Asia had the most pronounced increase in HF prevalence rate (AAPC = 1.35 [1.28-1.43]) and YLDs rate (AAPC = 1.32 [1.27-1.38]), while the highest HF prevalence rates per 100,000 population were observed in High-income North America (232 [185.4-292]). The prevalence and YLDs of HF increased in most countries except Australia, Canada, and Spain. The largest increase in HF prevalence rate was observed in China (AAPC = 1.39 [1.31-1.48]). By SDI quintile, the middle-SDI quintile countries had the largest increase in prevalence and YLDs rates. By sex, males had a higher prevalence rate per 100,000 population than females (158.0 [95% UI: 126.7-198.9] vs 137.6 [95% UI: 110.0-172.2]) in 2021. Among three age groups, the largest increase in HF prevalence from 1990 to 2021 was found in individuals aged 20-24 years (AAPC = 0.61 [0.6-0.61]). Among all causes of HF, cardiomyopathy and myocarditis accounted for the highest proportion (32.7%) of prevalence cases of HF in 2021, followed by congenital birth defects (27.3%), and rheumatic heart disease (23.8%). The BAPC analysis predicted that the cases of HF prevalence and YLDs would show a rising trend from 2022 to 2030.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;The burden of HF in adolescents and young adults aged 10-24 years was still increasi","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102998"},"PeriodicalIF":9.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906728","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":"Surgical interventions for spontaneous supratentorial intracerebral haemorrhage: a systematic review and network meta-analysis.","authors":"Jiayidaer Huan, Minghong Yao, Yu Ma, Fan Mei, Yanmei Liu, Lu Ma, Xiaochao Luo, Jiali Liu, Jianguo Xu, Chao You, Hunong Xiang, Kang Zou, Xiao Liang, Xin Hu, Ling Li, Xin Sun","doi":"10.1016/j.eclinm.2024.102999","DOIUrl":"10.1016/j.eclinm.2024.102999","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Surgical interventions for spontaneous supratentorial intracerebral haemorrhage (ICH) include conventional craniotomy (CC), decompressive craniectomy (DC), and minimally invasive surgery (MIS), with the latter encompassing endoscopic surgery (ES) and minimally invasive puncture surgery (MIPS). However, the superiority of surgery over conservative medical treatment (CMT) and the comparative benefits of different surgical procedures remain unclear. We aimed to evaluate the efficacy and safety of various surgical interventions for treating ICH.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this systematic review and network meta-analysis, we searched PubMed, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov from inception to June 16, 2024. Eligible studies were randomised controlled trials (RCTs) comparing surgery (i.e., CC, ES, MIPS, or DC) with CMT or comparing different types of surgeries in patients with spontaneous supratentorial ICH. Paired reviewers independently screened citations, assessed the risk of bias of included trials, and extracted data. Primary outcomes were good functional outcome and mortality at 6 months. Secondary outcomes were good functional outcome and mortality at different follow-up times, complications (rebleeding, brain infection, pulmonary infection), and hematoma evacuation rate. The frequentist pairwise and network meta-analysis (NMA) were performed. The GRADE approach was used to evaluate the certainty of evidence. This study is registered with PROSPERO, CRD42024518961.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Of the 8573 total records identified by our searches, 31 studies (6448 patients) were eligible for the systematic review and network analysis. Compared with CMT, moderate certainty evidence showed that surgery improved good functional outcome (risk ratio [RR] 1.31, 95% CI 1.13-1.52; risk difference [RD] 9.1%, 95% CI 3.8 to 15.3; &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt;  = 36%) and reduced mortality (RR 0.82, 95% CI 0.71-0.95; RD -5.1%, 95% CI -8.2 to -1.4; &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt;  = 14%). Moderate certainty evidence from NMA suggested that compared with CMT, both ES (RR 1.51, 95% CI 1.18-1.93; RD 9.4%, 95% CI 3.3-17.1) and MIPS (RR 1.48, 95% CI 1.24-1.76; RD 15.7%, 95% CI 7.9-24.9) improved good functional outcome at 6 months, and both ES (RR 0.66, 95% CI 0.52-0.85; RD -17.0%, 95% CI -24.0 to -7.5) and CC (RR 0.75, 95% CI 0.60-0.94; RD -6.3%, 95% CI -10.1 to -1.5) reduced mortality at 6 months, whereas MIPS and DC showed a trend, although not statistically significant, towards a reduction in mortality. ES and MIPS also reduced pulmonary infection risk (ES RR 0.39, 95% CI 0.23-0.69; MIPS RR 0.35, 95% CI 0.20-0.60; RD -5.3%, 95% CI -6.6 to -3.3). ES showed higher hematoma evacuation than CC (MD: 7.03, 95% CI: 3.42-10.65; &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;&lt;i&gt;2&lt;/i&gt;&lt;/sup&gt;  = 94%). No difference in rebleeding or brain infection was found between CC and MIS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Curren","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102999"},"PeriodicalIF":9.6,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of perioperative sintilimab plus platinum-based chemotherapy for potentially resectable stage IIIB non-small cell lung cancer (periSCOPE): an open-label, single-arm, phase II trial.","authors":"Xiangyang Yu, Chujian Huang, Longde Du, Chunguang Wang, Yikun Yang, Xin Yu, Shengcheng Lin, Chenglin Yang, Hongbo Zhao, Songhua Cai, Zhe Wang, Lixu Wang, Xiaotong Guo, Baihua Zhang, Zhentao Yu, Jie He, Kai Ma","doi":"10.1016/j.eclinm.2024.102997","DOIUrl":"10.1016/j.eclinm.2024.102997","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The absolute overall survival (OS) improvement with preoperative chemotherapy or chemoradiotherapy in locally advanced non-small cell lung cancer (NSCLC) patients is controversial and unsatisfactory. We designed this trial to explore the efficacy and safety of perioperative sintilimab plus platinum-based chemotherapy for potentially resectable stage IIIB NSCLC to facilitate further optimization of this therapeutic strategy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Patients diagnosed with stage IIIB NSCLC through invasive staging approaches and/or PET/CT scans and evaluated as having a high probability of radical resection of the primary lesion and metastatic lymph nodes with clear pathological margins by a multidisciplinary team were enrolled in this open-label, single-arm, phase II trial at a single centre in China. The participants received two cycles of intravenous neoadjuvant treatment with PD-1 inhibitor sintilimab (200 mg), pemetrexed (500 mg/m&lt;sup&gt;2&lt;/sup&gt;) for adenocarcinoma, paclitaxel (175 mg/m&lt;sup&gt;2&lt;/sup&gt;) or nab-paclitaxel (260 mg/m&lt;sup&gt;2&lt;/sup&gt;) for other histological subtypes, plus carboplatin (area under the curve 5) or cisplatin (75 mg/m&lt;sup&gt;2&lt;/sup&gt;) on the first day of each 3-week cycle. Surgical resection was performed 28-42 days later. After recovery from surgery, two cycles of adjuvant treatment were carried out in strict conformity with the neoadjuvant regimen, and then sintilimab maintenance monotherapy were given. The primary endpoint was major pathological response (MPR). The key secondary endpoints included the objective response rate (ORR), radical resection (R0) rate, pathological complete response (pCR) rate, event-free survival (EFS), disease-free survival (DFS), OS, treatment-related adverse events (TRAEs), surgical complications, and surgery delay rate. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2000040673).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Forty-one patients were assessed for eligibility between December 2020 and August 2022; 30 patients were enrolled and given two cycles of neoadjuvant chemoimmunotherapy (neoCIT). Nineteen patients achieved a radiographic partial response, resulting in an ORR of 63.3%. Although 26 patients (86.7%) experienced TRAEs during the neoadjuvant phase, only two patients (6.7%) had ≥ grade 3 TRAEs. Surgical resection was performed on 27 patients (90%), with two patients experienced surgical delay because of coronavirus disease 2019, and the R0 rate was 96.4%. Twelve patients (44.4%) in the per-protocol (PP) population achieved an MPR, including six patients (22.2%) with a pCR. The most common postoperative complications were atrial fibrillation (6, 22.2%), pneumonitis (5, 18.5%), and heart failure (4, 14.8%); no deaths occurred within 90 days after surgery. As of October 31, 2024, the median follow-up was 34.7 months. The estimated EFS and OS rates at 36 months in the intention-to-treat population were 42.8% and 70.1%, respectively, and th","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102997"},"PeriodicalIF":9.6,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885185","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":"Novel type 2 diabetes prediction score based on traditional risk factors and circulating metabolites: model derivation and validation in two large cohort studies.","authors":"Ruijie Xie, Christian Herder, Sha Sha, Lei Peng, Hermann Brenner, Ben Schöttker","doi":"10.1016/j.eclinm.2024.102971","DOIUrl":"10.1016/j.eclinm.2024.102971","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;We aimed to evaluate the incremental predictive value of metabolomic biomarkers for assessing the 10-year risk of type 2 diabetes when added to the clinical Cambridge Diabetes Risk Score (CDRS).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We utilized 86,232 UK Biobank (UKB) participants (recruited between 13 March 2006 and 1 October 2010) for model derivation and internal validation. Additionally, we included 4383 participants from the German ESTHER cohort (recruited between 1 July 2000 and 30 June 2002 for external validation). Participants were followed up for 10 years to assess the incidence of type 2 diabetes. A total of 249 NMR-derived metabolites were quantified using nuclear magnetic resonance (NMR) spectroscopy. Metabolites were selected with LASSO regression and model performance was evaluated with Harrell's C-index.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;11 metabolomic biomarkers, including glycolysis related metabolites, ketone bodies, amino acids, and lipids, were selected. In internal validation within the UKB, adding these metabolites significantly increased the C-index (95% confidence interval (95% CI)) of the clinical CDRS from 0.815 (0.800, 0.829) to 0.834 (0.820, 0.847) and the continuous net reclassification index (NRI) with 95% CI was 39.8% (34.6%, 45.0%). External validation in the ESTHER cohort showed a comparable statistically significant C-index increase from 0.770 (0.750, 0.791) to 0.798 (0.779, 0.817) and a continuous NRI of 33.8% (26.4%, 41.2%). A concise model with 4 instead of 11 metabolites yielded similar results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Adding 11 metabolites to the clinical CDRS led to a novel type 2 diabetes prediction model, we called UK Biobank Diabetes Risk Score (UKB-DRS), substantially outperformed the clinical CDRS. The concise version with 4 metabolites performed comparably. As only very few clinical information and a blood sample are needed for the UKB-DRS, and as high-throughput NMR metabolomics are becoming increasingly available at low costs, these models have considerable potential for routine clinical application in diabetes risk assessment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Funding: &lt;/strong&gt;The ESTHER study was funded by grants from the Baden-Württemberg state Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany), the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany), and the Saarland State Ministry of Health, Social Affairs, Women and the Family (Saarbrücken, Germany). The UK Biobank project was established through collaboration between various entities including the Wellcome Trust, the Medical Research Council, Department of Health, Scottish Government, and the Northwest Regional Development Agency. Additional funding was provided by the Welsh Assembly Government, British Heart Foundation, Cancer Research UK, and Diabetes UK, with support from the National Health Service (NHS). The","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102971"},"PeriodicalIF":9.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885391","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":"Worldwide patterns and trends in ovarian cancer incidence by histological subtype: a population-based analysis from 1988 to 2017.","authors":"Yi-Fan Wei, Li Ning, Yi-Lin Xu, Jing Ma, Dong-Run Li, Zan-Fei Feng, Fang-Hua Liu, Yi-Zi Li, He-Li Xu, Peng Li, Yong-Pei Yu, Dong-Hui Huang, Xiao-Ying Li, Song Gao, Chun-Qing Lin, Ting-Ting Gong, Qi-Jun Wu, Jing-He Lang","doi":"10.1016/j.eclinm.2024.102983","DOIUrl":"10.1016/j.eclinm.2024.102983","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is a heterogeneous malignancy with multiple histological subtypes, showing global variability in incidence. Temporal changes in diagnostic criteria and risk factors might influence the incidence and distribution of OC and its subtypes.</p><p><strong>Methods: </strong>This study analyzed incidence patterns (2013-2017) and trends (1988-1992 to 2013-2017) of OC and its subtypes across 65 and 40 countries, respectively. Data were extracted from the Cancer Incidence in Five Continents (CI5 Ⅻ) and CI5plus databases (accessed in June 2024). Annual percent changes were computed to describe trends in age-standardized rates (ASRs) of OC and its subtypes. Proportions of ASR for each subtype relative to the ASR of OC for individual countries were calculated.</p><p><strong>Findings: </strong>The incidence of OC displayed marked disparities across regions and Human Development Index (HDI), with the highest ASRs in Eastern and Central Europe and very high HDI regions, and the lowest in Africa, Asia, and medium HDI regions. Despite stable trend in ASRs of OC globally, notable declines were observed in Europe, America, and Oceania, in contrast to increases in Asian countries like Japan and South Korea. Globally, serous carcinomas remained the most prevalent subtype. European countries exhibited a higher proportion of serous carcinomas, while Asian countries had a higher proportion of endometrioid and clear cell carcinomas. Although trends in subtypes also remained stable, ASRs increased over time for serous carcinomas and germ cell tumor in most countries, while mucinous carcinomas and adenocarcinoma NOS showed a decline.</p><p><strong>Interpretation: </strong>Variations in global patterns and trends in OC incidence and its subtypes might be influenced by genetic and reproductive factors. Consequently, region-specific prevention strategies and ongoing surveillance are essential to mitigate the burden of OC.</p><p><strong>Funding: </strong>The National Key Research and Development Program of China (No.2022YFC2704205), the Natural Science Foundation of China (No.82073647, 82373674, and 82103914), Outstanding Scientific Fund of Shengjing Hospital, 345 Talent Project of Shengjing Hospital of China Medical University, the Max Planck - University of Helsinki Center from the Jane and Aatos Erkko Foundation (No.210046), the Max Planck Society (No.5714240218), the University of Helsinki (No.77204227), and the European Union (ERC Synergy, BIOSFER, 101071773).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"79 ","pages":"102983"},"PeriodicalIF":9.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885008","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}