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{"title":"Dexmedetomidine decreases cerebral hyperperfusion incidence following carotid stenting: A double-blind, randomized controlled trial.","authors":"Enqiang Chang, Lingzhi Wu, Xinyi Li, Jinpeng Zhou, Hui Zhi, Min Sun, Guanyu Chen, Jiaqi Bi, Li Li, Tianxiao Li, Daqing Ma, Jiaqiang Zhang","doi":"10.1016/j.medj.2024.09.012","DOIUrl":"https://doi.org/10.1016/j.medj.2024.09.012","url":null,"abstract":"<p><strong>Background: </strong>Cerebral hyperperfusion syndrome (CHS) is a severe complication after carotid artery stenting (CAS). Dexmedetomidine (Dex) is an α₂ adrenoceptor agonist with sedative, analgesic, and neuroprotective properties. This randomized, double-blind, placebo-controlled trial (ChiCTR1900024416) aims to investigate whether prophylactic low-dose Dex decreases CH-induced brain injury following CAS.</p><p><strong>Methods: </strong>After obtaining written informed consent, patients aged 18-80 who underwent CAS were enrolled between July 2019 and October 2022. Patients were randomly assigned to receive either intravenous Dex (0.1 μg/kg/h, until post-operative day 3) (n = 80) or placebo (normal saline) (n = 80). The primary endpoint was the incidence of CH and CHS assessed up to the third post-operative day. The secondary endpoints included National Institute of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) scores within 30 days of operation, extubation time, discharge from the hospital within 7 days post-operation, length of hospital stay post-operation, and all-cause 30-day mortality. Blood samples were collected before and after surgery for lipidomics, brain-derived neurotrophic factor (BDNF), and neurofilament light chain (Nfl) measurements. Acceptability, safety, and efficacy were evaluated by Cox model and logistic model.</p><p><strong>Findings: </strong>CH occurred in 30 (37.5%) of 80 patients who received a placebo compared to 9 (11.2%) of 80 patients given Dex (prevalence: odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.088-0.467; p < 0.001; incidence: hazard ratio [HR]: 0.27, 95% CI: 0.14-0.50; p < 0.001). CHS was significantly higher in the placebo group (13.75%) than in the Dex group (2.5%) (prevalence: [OR]: 0.161, 95% CI: 0.024-0.626; p = 0.020; incidence: [HR]: 0.17, 95% CI: 0.06-0.52; p = 0.009). Dex significantly upregulated BDNF, decreased Nfl, and uniquely increased lysophosphatidylethanolamine.</p><p><strong>Conclusions: </strong>A low prophylactic dose of Dex significantly reduced the incidence of CH and CHS up to 72 h after CAS.</p><p><strong>Funding: </strong>This work was funded by National Natural Science Foundation of China (no. 82271288) and the Henan Provincial Science and Technology Research Project (nos. 242300421192 and JQRC2023004).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting HLA-E-overexpressing cancers with a NKG2A/C switch receptor.","authors":"Michelle Sætersmoen, Ivan S Kotchetkov, Lamberto Torralba-Raga, Jorge Mansilla-Soto, Ebba Sohlberg, Silje Zandstra Krokeide, Quirin Hammer, Michel Sadelain, Karl-Johan Malmberg","doi":"10.1016/j.medj.2024.09.010","DOIUrl":"10.1016/j.medj.2024.09.010","url":null,"abstract":"<p><strong>Background: </strong>Human leukocyte antigen (HLA)-E is overexpressed by a large proportion of solid tumors, including malignant glioblastoma, and acts as a major checkpoint for NKG2A⁺ CD8⁺ T cells and natural killer (NK) cells in the tumor microenvironment and circulation. This axis operates alongside PD-L1 to inhibit effector responses by T and NK cells.</p><p><strong>Methods: </strong>We engineered a chimeric A/C switch receptor, combining the high HLA-E binding affinity of the NKG2A receptor ectodomain with the activating signaling of the NKG2C receptor endodomain. The cytotoxic function of A/C switch-transduced NK and T cells was evaluated against tumor cells with varying levels of HLA-E expression. In vivo efficacy was assessed using a xenograft model of glioblastoma.</p><p><strong>Findings: </strong>A/C switch-transduced NK and T cells exhibited superior and specific cytotoxicity against tumor cells with medium to high HLA-E expression. A/C switch-expressing human T cells demonstrated enhanced anti-tumor function in a glioblastoma xenograft model. The activity of the modified T cells was governed by an equilibrium between A/C switch levels and HLA-E expression, creating a therapeutic window to minimize on-target, off-tumor toxicities. Normal cells remained insensitive to A/C switch T cells, even after interferon (IFN)-γ pretreatment to induce HLA-E expression.</p><p><strong>Conclusions: </strong>The A/C switch receptor effectively targets tumor cells expressing high levels of HLA-E, either alone or in combination with other engineered specificities, to overcome the suppressive NKG2A/HLA-E checkpoint. This approach offers a promising therapeutic strategy with a favorable safety profile for targeting HLA-E-overexpressing tumors.</p><p><strong>Funding: </strong>This work was funded by The Research Council of Norway, the Norwegian Cancer Society, and the National Cancer Institute.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.","authors":"Dimitrios C Ladakis, Kimystian L Harrison, Matthew D Smith, Krista Solem, Sachin Gadani, Larissa Jank, Soonmyung Hwang, Farzaneh Farhadi, Blake E Dewey, Kathryn C Fitzgerald, Elias S Sotirchos, Shiv Saidha, Peter A Calabresi, Pavan Bhargava","doi":"10.1016/j.medj.2024.09.011","DOIUrl":"10.1016/j.medj.2024.09.011","url":null,"abstract":"<p><strong>Background: </strong>Bile acid metabolism is altered in multiple sclerosis (MS) and tauroursodeoxycholic acid (TUDCA) supplementation ameliorated disease in mouse models of MS.</p><p><strong>Methods: </strong>Global metabolomics was performed in an observational cohort of people with MS, followed by pathway analysis to examine relationships between baseline metabolite levels and subsequent brain and retinal atrophy. A double-blind, placebo-controlled trial was completed in people with progressive MS (PMS), randomized to receive either TUDCA (2 g/day) or placebo for 16 weeks. Participants were followed with serial clinical and laboratory assessments. Primary outcomes were safety and tolerability of TUDCA, and exploratory outcomes included changes in clinical, laboratory, and gut microbiome parameters.</p><p><strong>Findings: </strong>In the observational cohort, higher primary bile acid levels at baseline predicted slower whole-brain atrophy, brain substructure atrophy, and specific retinal layer atrophy. In the clinical trial, 47 participants were included in our analyses (21 in placebo arm, 26 in TUDCA arm). Adverse events did not differ significantly between arms (p = 0.77). The TUDCA arm demonstrated increased serum levels of multiple bile acids. No significant differences were noted in clinical or fluid biomarker outcomes. Central memory CD4⁺ and Th1/17 cells decreased, while CD4⁺ naive cells increased in the TUDCA arm compared to placebo. Changes in the composition and function of gut microbiota were also noted between the two groups.</p><p><strong>Conclusions: </strong>Bile acid metabolism in MS is linked to brain and retinal atrophy. TUDCA supplementation in PMS is safe, tolerable, and has measurable biological effects that warrant further evaluation in larger trials with a longer treatment duration.</p><p><strong>Funding: </strong>National MS Society grant RG-1707-28601 to P.B., R01 NS082347 from the National Institute of Neurological Disorders and Stroke to P.A.C., and National MS Society grant RG-1606-08768 to S.S.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of PSA and survival in metastatic hormone-sensitive prostate cancer treated with rezvilutamide plus ADT in the CHART trial.","authors":"Xiaojie Bian, Weijie Gu, Xuepei Zhang, Liping Xie, Shaogang Wang, Benkang Shi, Ting Sun, Shaozhong Wei, Zhiliang Weng, Shujie Xia, Bangmin Han, Zhuoqun Xu, Jinchun Xing, Dahong Zhang, Danfeng Xu, Chuanjun Du, Chaohong He, Qilin Wang, Xinfeng Yang, Jianpo Lian, Wenliang Wang, Dingwei Ye","doi":"10.1016/j.medj.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.medj.2024.09.009","url":null,"abstract":"<p><strong>Background: </strong>This exploratory analysis of the CHART trial (ClinicalTrials.gov: NCT03520478) investigated prostate-specific antigen (PSA) kinetics and the correlation between PSA and survival outcomes in high-volume, metastatic, hormone-sensitive prostate cancer (mHSPC).</p><p><strong>Methods: </strong>A total of 654 patients were randomized 1:1 to receive either rezvilutamide plus androgen deprivation therapy (ADT; n = 326) or bicalutamide plus ADT (n = 328). PSA kinetics were evaluated, and the correlation between survival and the achievement of undetectable PSA (≤0.2 ng/mL) or ≥90% PSA reduction (PSA90) was assessed.</p><p><strong>Findings: </strong>The rezvilutamide group exhibited higher proportions of ≥50% PSA reduction (PSA50; 98.2% vs. 87.5%), PSA90 (88.7% vs. 63.1%), and undetectable PSA (38.3% vs. 17.7%) responses compared to the bicalutamide group by 3 months. The rezvilutamide group demonstrated superior efficacy in delaying PSA progression compared to the bicalutamide group (hazard ratio [HR] 0.21, 95% confidence interval 0.16-0.27). The achievement of undetectable PSA and PSA90 by 6 months in the rezvilutamide group was associated with prolonged overall survival (undetectable PSA, HR = 0.34; PSA90, HR = 0.22), radiographic progression-free survival (HR = 0.36, HR = 0.26), time to PSA progression (HR = 0.25, HR = 0.17), and time to castration resistance (HR = 0.34, HR = 0.23) compared to those who did not achieve these PSA milestones. Stratification by baseline PSA level revealed consistent survival improvements with rezvilutamide plus ADT across quartiles.</p><p><strong>Conclusions: </strong>PSA kinetics is a valuable prognostic factor in mHSPC treated with rezvilutamide plus ADT, and the achievement of undetectable PSA and PSA90 is associated with improved survival. These findings highlight the importance of monitoring PSA kinetics in the management of mHSPC.</p><p><strong>Funding: </strong>This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluid biomarkers in the context of amyloid-targeting disease-modifying treatments in Alzheimer's disease.","authors":"Yan Hu, Min Cho, Pallavi Sachdev, Jeffrey Dage, Suzanne Hendrix, Oskar Hansson, Randall J Bateman, Harald Hampel","doi":"10.1016/j.medj.2024.08.004","DOIUrl":"10.1016/j.medj.2024.08.004","url":null,"abstract":"<p><p>Clinical management and therapeutics development for Alzheimer's disease (AD) have entered a new era, with recent approvals of monoclonal antibody therapies targeting the underlying pathophysiology of the disease and modifying its trajectory. Imaging and fluid biomarkers are becoming increasingly important in the clinical development of AD therapeutics. This review focuses on the evidence of fluid biomarkers from recent amyloid-β-targeting clinical trials, summarizing biomarker data across 12 trials. It further proposes a simple framework to put biomarker guidance in the context of amyloid-pathway-targeted disease modification, delineates factors that impact biomarker data in clinical trials, and highlights knowledge gaps and future directions. Increased knowledge and data on biomarkers in the context of disease progression and disease modification will help to better design future AD trials and guide the clinical management of patients on AD-modifying therapies, bringing us closer to the implementation of precision medicine in AD.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global burden and management of women with epilepsy in pregnancy: A modeling study.","authors":"Leihao Sha, Ze Cao, Yutong Fu, Yifei Duan, Yilin Xia, Xiaoru Feng, Torbjörn Tomson, Xiaolei Xie, Lei Chen","doi":"10.1016/j.medj.2024.07.005","DOIUrl":"10.1016/j.medj.2024.07.005","url":null,"abstract":"<p><strong>Background: </strong>Most pregnant women with epilepsy do not receive proper medical care, which creates a special burden worldwide. We aimed to qualify this special global burden and assess the impact of different clinical management strategies to reduce it.</p><p><strong>Methods: </strong>The data used in this study were extracted from articles published between 2005 and 2022. We calculated the economic costs associated with major burdens experienced by pregnant women with epilepsy. We developed a microsimulation model to estimate the different effects of various interventions and their combinations as integrated strategies for pregnant women with epilepsy and related burden reduction. We also compared the regional differences in disease burden and interventions.</p><p><strong>Findings: </strong>The total economic burden for pregnant women with epilepsy is estimated to reach $1.8 billion globally annually, which is more than three times the burden for epilepsy alone. Folic acid supplementation is projected to be the most effective intervention, with a 9.1% reduction in major congenital malformations, a 14.9% reduction in autism spectrum disorder, and a 10.8% reduction in offspring-related economic burden globally annually. Integrated strategies are associated with a reduced economic burden of up to $37.7 million annually globally. Folic acid supplementation is the most effective intervention in high- and upper-middle-income countries, whereas changes in antiseizure medication prescriptions are more effective in lower-middle- and low-income countries.</p><p><strong>Conclusion: </strong>This study highlights the huge burden for pregnant women with epilepsy and actions that must be taken to improve their quality of life.</p><p><strong>Funding: </strong>This work was supported by the Sichuan Science and Technology Program (2023YFS0047).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NanoRanger enables rapid single-base-pair resolution of genomic disorders.","authors":"Yingzi Zhang, Chongwei Bi, Seba Nadeef, Sateesh Maddirevula, Mashael Alqahtani, Fowzan S Alkuraya, Mo Li","doi":"10.1016/j.medj.2024.07.003","DOIUrl":"10.1016/j.medj.2024.07.003","url":null,"abstract":"<p><strong>Background: </strong>Delineating base-resolution breakpoints of complex rearrangements is crucial for an accurate clinical understanding of pathogenic variants and for carrier screening within family networks or the broader population. However, despite advances in genetic testing using short-read sequencing (SRS), this task remains costly and challenging.</p><p><strong>Methods: </strong>This study addresses the challenges of resolving missing disease-causing breakpoints in complex genomic disorders with suspected homozygous rearrangements by employing multiple long-read sequencing (LRS) strategies, including a novel and efficient strategy named nanopore-based rapid acquisition of neighboring genomic regions (NanoRanger). NanoRanger does not require large amounts of ultrahigh-molecular-weight DNA and stands out for its ease of use and rapid acquisition of large genomic regions of interest with deep coverage.</p><p><strong>Findings: </strong>We describe a cohort of 16 familial cases, each harboring homozygous rearrangements that defied breakpoint determination by SRS and optical genome mapping (OGM). NanoRanger identified the breakpoints with single-base-pair resolution, enabling accurate determination of the carrier status of unaffected family members as well as the founder nature of these genomic lesions and their frequency in the local population. The resolved breakpoints revealed that repetitive DNA, gene regulatory elements, and transcription activity contribute to genome instability in these novel recessive rearrangements.</p><p><strong>Conclusions: </strong>Our data suggest that NanoRanger greatly improves the success rate of resolving base-resolution breakpoints of complex genomic disorders and expands access to LRS for the benefit of patients with Mendelian disorders.</p><p><strong>Funding: </strong>M.L. is supported by KAUST Baseline Award no. BAS/1/1080-01-01 and KAUST Research Translation Fund Award no. REI/1/4742-01.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.","authors":"Hui Wang, Zhuoran Yao, Kai Kang, Lin Zhou, Weigang Xiu, Jianguo Sun, Conghua Xie, Min Yu, Yanying Li, Yan Zhang, Yue Zheng, Guo Lin, Xiangyu Pan, Yijun Wu, Ren Luo, Laduona Wang, Min Tang, Shuangsi Liao, Jiang Zhu, Xiaojuan Zhou, Xuanwei Zhang, Yong Xu, Yongmei Liu, Feng Peng, Jin Wang, Lisha Xiang, Limei Yin, Lei Deng, Meijuan Huang, Youling Gong, Bingwen Zou, Hui Wang, Lin Wu, Zhiyong Yuan, Nan Bi, Min Fan, Yaping Xu, Ruizhan Tong, Linglu Yi, Lu Gan, Jianxin Xue, Xianming Mo, Chong Chen, Feifei Na, You Lu","doi":"10.1016/j.medj.2024.06.002","DOIUrl":"10.1016/j.medj.2024.06.002","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.</p><p><strong>Methods: </strong>We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety.</p><p><strong>Findings: </strong>Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1⁺ PD-1⁺ CD8⁺ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3).</p><p><strong>Conclusions: </strong>These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation.</p><p><strong>Funding: </strong>This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual HER2 inhibition: Is two better than one?","authors":"Matthew R Strickland, Samuel J Klempner","doi":"10.1016/j.medj.2024.07.008","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.008","url":null,"abstract":"<p><p>Li et al. present data from a randomized frontline phase II trial in HER2+ gastroesophageal cancers exploring dual targeting of HER2 with HLX22 (a novel HER2-specific antibody) with HLX02 (a trastuzumab biosimilar) and capecitabine/oxaliplatin chemotherapy. While the objective response and progression-free survival are encouraging, the future development of the combination in a crowded HER2 space remains unclear.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic subgroup in serologically active clinically quiescent systemic lupus erythematosus: A cluster analysis based on CSTAR cohort.","authors":"Yufang Ding, Yangzhong Zhou, Feng Zhan, Jian Xu, Xinwang Duan, Hui Luo, Cheng Zhao, Min Yang, Rui Wu, Lijun Wu, Zhen Chen, Wei Wei, Can Huang, Chanyuan Wu, Shangzhu Zhang, Nan Jiang, Dong Xu, Xiaomei Leng, Qian Wang, Xinping Tian, Mengtao Li, Xiaofeng Zeng, Jiuliang Zhao","doi":"10.1016/j.medj.2024.06.005","DOIUrl":"10.1016/j.medj.2024.06.005","url":null,"abstract":"<p><strong>Background: </strong>Serologically active clinically quiescent (SACQ) is a state within systemic lupus erythematosus (SLE) characterized by elevated serologic markers without clinical activity. The heterogeneity in SACQ patients poses challenges in disease management. This multicenter prospective study aimed to identify distinct SACQ subgroups and assess their utility in predicting organ damage.</p><p><strong>Methods: </strong>SACQ was defined as a sustained period of at least 6 months with persistent serologic activity, marked by positive anti-double-stranded DNA (dsDNA) antibodies and/or hypocomplementemia, and without clinical activity. Cluster analysis was employed, utilizing 16 independent components to delineate phenotypes.</p><p><strong>Findings: </strong>Among the 4,107 patients with SLE, 990 (24.1%) achieved SACQ within 2.0 ± 2.3 years on average. Over a total follow-up of 7,105.1 patient years, 340 (34.3%) experienced flares, and 134 (13.5%) developed organ damage. Three distinct SACQ subgroups were identified. Cluster 1 (n = 219, 22.1%) consisted predominantly of elderly males with a history of major organ involvement at SLE diagnosis, showing the highest risk of severe flares (16.4%) and organ damage (27.9%). Cluster 2 (n = 279, 28.2%) was characterized by milder disease and a lower risk of damage accrual (5.7%). Notably, 86 patients (30.8%) in cluster 2 successfully discontinued low-dose glucocorticoids, with 49 of them doing so without experiencing flares. Cluster 3 (n = 492, 49.7%) featured the highest proportion of lupus nephritis and a moderate risk of organ damage (11.8%), with male patients showing significantly higher risk of damage (hazard ratio [HR] = 4.51, 95% confidence interval [CI], 1.82-11.79).</p><p><strong>Conclusion: </strong>This study identified three distinct SACQ clusters, each with specific prognostic implications. This classification could enhance personalized management for SACQ patients.</p><p><strong>Funding: </strong>This work was funded by the National Key R&D Program (2021YFC2501300), the Beijing Municipal Science & Technology Commission (Z201100005520023), the CAMS Innovation Fund (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-009).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}