MedPub Date : 2025-09-12DOI: 10.1016/j.medj.2025.100842
Lorenza Bartu, Jeremiah J Faith
{"title":"Searching for the perfect match: MINDFUL trial pairs FMT and fiber for ulcerative colitis.","authors":"Lorenza Bartu, Jeremiah J Faith","doi":"10.1016/j.medj.2025.100842","DOIUrl":"10.1016/j.medj.2025.100842","url":null,"abstract":"<p><p>Every trial of fecal microbiota transplantation for ulcerative colitis inspires the same question at seminars and journal clubs: can you combine FMT with a diet or fiber to improve strain engraftment and outcomes? The MINDFUL clinical trial explores this question by testing the impact of FMT with or without psyllium fiber supplementation in 27 ulcerative colitis patients.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 9","pages":"100842"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058628","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}
MedPub Date : 2025-09-08DOI: 10.1016/j.medj.2025.100802
Yakai Fu, Zhiwei Chen, Jie Chen, Wanlong Wu, Liyang Gu, Yiyangzi Ma, Runci Wang, Kaiwen Wang, Cuiying Xie, Yi Chen, Jiayi Cai, Qiong Fu, Xiaodong Wang, Shuang Ye
{"title":"Efficacy of JAK inhibitor combined with protein A immunoadsorption in MDA5+ dermatomyositis with RPILD: A real-world study.","authors":"Yakai Fu, Zhiwei Chen, Jie Chen, Wanlong Wu, Liyang Gu, Yiyangzi Ma, Runci Wang, Kaiwen Wang, Cuiying Xie, Yi Chen, Jiayi Cai, Qiong Fu, Xiaodong Wang, Shuang Ye","doi":"10.1016/j.medj.2025.100802","DOIUrl":"10.1016/j.medj.2025.100802","url":null,"abstract":"<p><strong>Background: </strong>Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) with rapidly progressive interstitial lung disease (RPILD) is a fatal disease. Although Janus kinase inhibitors (JAKi) hold their promise in treating MDA5+ DM, regimen for RPILD is still urgently needed to improve the adverse prognosis.</p><p><strong>Methods: </strong>Based on a large inception cohort of MDA5+ DM, patients with RPILD (oxygen index [OI] < 300 within the first 3 months of disease duration) were included. Patients who received protein A immunoadsorption plus a JAKi were compared to those treated with JAKi alone. Propensity score matching (PSM) was performed to adjust confounding factors. Survival analysis was conducted to evaluate the efficacy of immunoadsorption add-on.</p><p><strong>Findings: </strong>From October 2017 to April 2024, a total of 152 newly diagnosed MDA5+ DM patients with RPILD were eligible for analyses. Thirty-four patients who underwent immunoadsorption with JAKi (ProJAK group) and 68 patients who received JAKi with or without other immunosuppressants combination (JAK group) as controls were compared after 1:2 PSM. The 6-month transplantation-free survival was significantly improved from 16.2% in the JAK group to 41.2% in the ProJAK group (p = 0.004). Subgroup analysis suggested that ProJAK therapy tended to have a more significant survival gain in patients with OI < 200. The most common adverse effect of ProJAK was transient immunoglobin decrease, but the infectious rate was similar between the 2 groups.</p><p><strong>Conclusions: </strong>Immunoadsorption in combination with JAKi might be a promising treatment approach for MDA5+ DM patients with RPILD.</p><p><strong>Funding: </strong>This work was supported by NFSC and SHDC.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100802"},"PeriodicalIF":11.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030982","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":"Real-time diagnosis of cholangiocarcinoma by combining digestive endoscopy and optic fiber biosensors based on bile clusterin.","authors":"Long Gao, Baoquan Xiao, Yanyan Lin, Xidong Fang, Shun He, Mingzhen Bai, Lingen Zhang, Yanni Ma, Ningning Mi, Wenkang Fu, Chongfei Huang, Liang Tian, Jinyu Zhao, Ruyang Zhong, Zhen Liu, Yanxian Ren, Chao Zhang, Ruoshui Wang, Chenjun Tian, Hui Sun, Emmanuel Melloul, Qiangqiang Zhang, Jinqiu Yuan, Ping Yue, Liyun Ding, Wenbo Meng","doi":"10.1016/j.medj.2025.100843","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100843","url":null,"abstract":"<p><strong>Background: </strong>Early diagnosis of cholangiocarcinoma (CCA) remains challenging, but liquid biopsy is emerging as a promising detection strategy. Here, we identified a novel bile biomarker for CCA and developed an optic fiber biosensor integrated with digestive endoscopy for real-time diagnosis in vivo.</p><p><strong>Methods: </strong>A total of 583 subjects and two proteomic analyses were used to screen and validate biomarkers for CCA, and then the corresponding antibodies were generated to construct a surface plasmon resonance (SPR)-based optic fiber biosensor. The diagnostic performance of the biosensor was validated in 120 patients in vitro, and its biological characteristics were assessed under various physiological conditions. Finally, its real-time detection and biosafety in vivo were verified in pigs and patients.</p><p><strong>Findings: </strong>Clusterin (CLU) has been identified as a promising biomarker for CCA. Anti-CLU antibodies can specifically bind antigens with a K<sub>D</sub> value of 0.231 nM, and the diameter of the antibody-coated biosensor is only 0.488 mm. The optic fiber biosensor can accurately detect different concentrations of CLU with an R<sup>2</sup> value of 0.989, and it cannot be disturbed by other free proteins, ions, or different temperatures, pH levels, and colors. The biosensor can identify CCA within 2 s with an area under curve (AUC) of 0.854. Moreover, the biosensor can be easily introduced into porcine bile ducts via digestive endoscopy with excellent biocompatibility. Then, the biosensor was applied to three patients with non-calculous biliary strictures, and the results of real-time detection matched postoperative pathology.</p><p><strong>Conclusions: </strong>The CLU-based biosensor-endoscopy system enables accurate diagnosis of CCA through real-time in vivo detection, offering significant clinical translational potential.</p><p><strong>Funding: </strong>Funding information is shown in the acknowledgments.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100843"},"PeriodicalIF":11.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034257","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}
MedPub Date : 2025-09-01DOI: 10.1016/j.medj.2025.100841
Eugenia Z Ong, Jia Xin Yee, Clara W Koh, Justin S Ooi, Christine Y L Tham, Kuan Rong Chan, Bettie W Kareko, Zoe L Lyski, Vianney Tricou, Hansi Dean, Ralph Braun, Shirin Kalimuddin, Jenny G Low, William B Messer, Mayuri Sharma, Eng Eong Ooi
{"title":"Dengue virus infection reprograms baseline innate immune gene expression.","authors":"Eugenia Z Ong, Jia Xin Yee, Clara W Koh, Justin S Ooi, Christine Y L Tham, Kuan Rong Chan, Bettie W Kareko, Zoe L Lyski, Vianney Tricou, Hansi Dean, Ralph Braun, Shirin Kalimuddin, Jenny G Low, William B Messer, Mayuri Sharma, Eng Eong Ooi","doi":"10.1016/j.medj.2025.100841","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100841","url":null,"abstract":"<p><strong>Background: </strong>All three dengue vaccines that have completed phase 3 clinical trials have shown greater efficacy in dengue-seropositive compared to dengue-seronegative individuals. This includes the live-attenuated tetravalent dengue vaccine TAK-003, where immunogenicity in baseline seronegative individuals remains lower after two doses, despite seroconversion after the first dose, compared to baseline seropositive individuals after one dose.</p><p><strong>Methods: </strong>A whole-genome microarray was used to analyze the host response to TAK-003. Bulk whole-blood RNA sequencing was used to confirm pre-vaccination baseline gene expression differences between seronegative and seropositive individuals.</p><p><strong>Findings: </strong>We found that the host response to TAK-003 in baseline seropositive individuals was driven, at least in part, by reprogrammed innate immune response from prior dengue virus (DENV) infection. Indeed, three independent cohorts of volunteers showed differential immune gene expression between dengue-seropositive compared to dengue-seronegative individuals at baseline. Gene modules related to the cell cycle were positively enriched, while innate immune gene modules were negatively enriched, in dengue-seropositive compared to dengue-seronegative subjects in all 3 cohorts. Remarkably, while a single DENV infection reprogrammed the gene expression of innate immune markers, including those implicated in dengue pathogenesis and disease severity, vaccination did not show evidence of similar innate immune reprogramming.</p><p><strong>Conclusions: </strong>Our findings suggest a lasting effect of DENV infection on the innate immune system that potentially impacts vaccination outcome and secondary dengue pathogenesis.</p><p><strong>Funding: </strong>The DEN-210 clinical trial and gene expression analyses were funded by Takeda Vaccines. The cohort studies in Singapore were funded by the National Medical Research Council.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100841"},"PeriodicalIF":11.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030809","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}
MedPub Date : 2025-08-29DOI: 10.1016/j.medj.2025.100840
Kleio-Maria Verrou, Nikolaos I Vlachogiannis, Argyrios N Theofilopoulos, Maria Tektonidou, Georgios Kollias, Christoforos Nikolaou, Petros P Sfikakis
{"title":"Machine learning-based identification of a transcriptomic blood signature discriminating between systemic autoimmunity and infection.","authors":"Kleio-Maria Verrou, Nikolaos I Vlachogiannis, Argyrios N Theofilopoulos, Maria Tektonidou, Georgios Kollias, Christoforos Nikolaou, Petros P Sfikakis","doi":"10.1016/j.medj.2025.100840","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100840","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic responses against self and foreign antigens in systemic autoimmunity and infection, respectively, engage similar immunologic components, thus lacking distinguishing diagnostic biomarkers. Herein, we tested whether whole-blood transcriptome analysis discriminates autoimmune from infectious diseases.</p><p><strong>Methods: </strong>We applied nested cross-validation methodology to tune and validate random forests, k-nearest neighbors, and support vector machines, using a new preprocessing method on 22 publicly available datasets, including 594 patients with a broad spectrum of systemic autoimmune diseases and 615 patients with diverse viral, bacterial, and parasitic infections.</p><p><strong>Findings: </strong>Our preprocessing method tackled RNA sequencing batch effects by sorting the genes within each sample according to individual relative expression values and discriminated between the corresponding pathologies with 98% accuracy versus 63% when using raw values. This model was further tested in external datasets comprising various autoimmune diseases and infections new to its training process, yielding accuracies ranging between 80% and 96%. Enrichment analyses of 457 of the most informative genes identified SAP1, ELF1/4, and FLI1 transcription factors among the significant upstream regulators and revealed several key processes and pathways, such as autophagy, DNA damage response, and NOTCH signaling. A subset of 24 genes, including the inflammation-related genes RPL7, TLK2, and ANK2, distinguished between autoimmune and infectious diseases with 89% accuracy.</p><p><strong>Conclusions: </strong>Using a novel batch-correction algorithm, this analysis may provide a new mechanistic understanding of the pathogenic autoimmune response, as well as biomarkers for differential diagnoses of the corresponding pathologies in patients presenting with inflammatory disorders.</p><p><strong>Funding: </strong>This work was funded by the European Regional Development Fund NSRF 2014-2020, no. MIS5002802.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100840"},"PeriodicalIF":11.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008410","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":"Anti-PD-1 antibody plus anlotinib vs. anlotinib alone in patients with refractory chondrosarcoma: A multicenter, non-randomized phase 2 FLAIL-C trial.","authors":"Binghao Li, Lu Xie, Junbo Liang, Yaling Jiang, Keyi Wang, Yunxia Liu, Nong Lin, Xin Huang, Kuo Zhao, Gentao Fan, Meng Liu, Xiaobo Yan, Hao Qu, Hengyuan Li, Jilong Yang, Guangxin Zhou, Zhaoming Ye","doi":"10.1016/j.medj.2025.100809","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100809","url":null,"abstract":"<p><strong>Background: </strong>There is no standard systemic therapy for unresectable chondrosarcoma. The purpose of this study is to explore the efficacy of combination therapy with an anti-PD-1 antibody and anlotinib in patients with advanced chondrosarcoma.</p><p><strong>Methods: </strong>Patients with dedifferentiated or high-grade conventional chondrosarcoma were eligible. Anlotinib was administered at 12 mg orally once a day from day 1 to 14 every 3 weeks in all participants. In the combination treatment arm, patients received an additional anti-PD-1 antibody at 200 mg every 3 weeks. The primary endpoint was the 6-month progression-free survival rate (PFSR). Biomarker analyses for therapeutic effectiveness were conducted.</p><p><strong>Findings: </strong>70 patients (32 with dedifferentiated and 38 with conventional chondrosarcoma) were enrolled in the study. After a medium follow-up of 15.6 months, combination treatment showed significantly improved outcomes compared to anlotinib alone in the entire population, with a higher 6-month PFSR (60.0% versus 31.4%). The PFS-event inverse probability weighting adjusted Cox model evaluation also revealed a significant benefit of combination treatment (hazard ratio = 0.14, 95% confidence interval [CI]: 0.07-0.30, p < 0.001). Patients with dedifferentiated chondrosarcoma benefited the most from the combination treatment, with improvements in objective response rate (33.3% versus 9.1%), 6-month PFSR (57.1% versus 9.1%), median PFS (7.0 months versus 3.8 months), and 1-year overall survival rate (42.9% versus 18.2%). Effector memory T cells were significantly associated with treatment response (p < 0.001).</p><p><strong>Conclusions: </strong>The combination treatment demonstrated promising efficacy in advanced chondrosarcoma, particularly for dedifferentiated cases (ClinicalTrials.gov: NCT05193188).</p><p><strong>Funding: </strong>This trial was supported by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100809"},"PeriodicalIF":11.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971990","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":"Short-course-based TNT with or without PD-1 inhibitor for pMMR locally advanced rectal cancer: Phase 2 results of a randomized trial (STELLAR II).","authors":"Yuan Tang, Hao-Yue Li, Li-Chun Wei, Ning Li, Wen-Jue Zhang, Yu-Fei Lu, Fei-Yan Deng, Tong-Zhen Xu, Jia-Cheng Shuai, Zi-Fa Lei, Xian-Yu Meng, Shu-Nan Qi, Yong-Wen Song, Wen-Wen Zhang, Hao Jing, Gong Li, Shi-Xin Liu, Ying-Jie Wang, Zheng Liu, Hui-Ying Ma, Ning-Yu Wang, Bo Chen, Shu-Lian Wang, Ye-Xiong Li, Li-Na Zhao, Jian-Qiang Tang, Zheng Jiang, Ying-Gang Chen, Hai-Tao Zhou, Chen Hu, Jing Jin","doi":"10.1016/j.medj.2025.100807","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100807","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic efficacy and mode of combining immunotherapy with neoadjuvant chemoradiotherapy in proficient mismatch repair (pMMR)/microsatellite stable (MSS) locally advanced rectal cancer (LARC) remain uncertain.</p><p><strong>Methods: </strong>In this multicenter, randomized, seamless phase 2/3 trial (ClinicalTrials.gov: NCT05484024), eligible participants were randomly assigned (1:1) to receive short-course radiotherapy (SCRT) (5 Gy × 5), followed by 4 cycles of capecitabine and oxaliplatin or 6 cycles of leucovorin, oxaliplatin, and fluorouracil, with (iTNT group) or without (total neoadjuvant therapy [TNT] group) 4 cycles of sintilimab. Following neoadjuvant therapy, participants underwent surgery or a watch-and-wait strategy based on clinical complete response. The primary endpoints were the complete response (CR) rate for phase 2 and the 3-year disease-free survival (DFS) rate for phase 3.</p><p><strong>Findings: </strong>218 patients were randomized to the iTNT group (n = 110) and the TNT group (n = 108). All patients completed SCRT, with 88.2% in the iTNT group and 93.5% in the TNT group completing 4 cycles of neoadjuvant treatment. The CR rate was significantly higher in the iTNT group (45.5% vs. 25.0%; p = 0.003). Grade 3-4 treatment-related adverse events were reported in 34.5% of the iTNT group and 19.4% of the TNT group (p = 0.012), with thrombocytopenia, diarrhea, leukopenia, and neutropenia being the most frequently observed. Grade 3-4 immune-related adverse events occurred in 5.5% of patients in the iTNT group.</p><p><strong>Conclusions: </strong>The addition of the PD-1 inhibitor sintilimab significantly enhances the CR rate compared to SCRT-based TNT, with favorable tolerability in patients with pMMR/MSS LARC.</p><p><strong>Funding: </strong>This work was funded by the National Natural Science Foundation of China (82473248) and the Shenzhen Medical Research Fund (C2301001).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100807"},"PeriodicalIF":11.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144972006","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":"Trends and sociodemographic patterns in hypertension prevalence and treatment in China.","authors":"Xue Cao, Xin Wang, Yixin Tian, Nuerguli Tuerdi, Congyi Zheng, Weiping Li, Xuyan Pei, Fan Li, Chenye Chang, Jialu Yang, Qinglan Jia, Zugui Zhang, Arun Chockalingam, Zengwu Wang","doi":"10.1016/j.medj.2025.100808","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100808","url":null,"abstract":"<p><strong>Background: </strong>Hypertension is a significant public health challenge in China, but evidence of current status and trends for hypertension prevalence and management is limited.</p><p><strong>Methods: </strong>Data were derived from two nationally representative surveys including 750,208 Chinese adults. All analyses accounted for complex sample design weights. Hypertension was defined as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg and/or use of antihypertensive medication within 2 weeks.</p><p><strong>Findings: </strong>The weighted prevalence of hypertension in 2021-2022 was 31.6% (95% confidence interval [CI] 30.1%-33.0%), representing a significantly absolute increase of 8.4% (95% CI 6.5%-10.2%) from 2012-2015 to 2021-2022. The prevalence of isolated systolic hypertension and isolated diastolic hypertension in 2021-2022 was 9.3% and 5.3%, respectively. In 2021-2022, the weighted rates of hypertension awareness, treatment, and control were 43.3% (95% CI 41.5%-45.2%), 38.7% (95% CI 36.9%-40.6%), and 12.9% (95% CI 11.6%-14.4%), respectively. The increases in hypertension prevalence were particularly pronounced among men and rural residents, who also tended to have a lower level of hypertension management. Age-standardized hypertension prevalence was 31.2% (95% CI 31.0%-31.4%) in the 2021-2022 survey and 22.3% (95% CI 22.2%-22.5%) in the 2012-2015 survey, respectively.</p><p><strong>Conclusions: </strong>Hypertension prevalence in China has risen, while awareness, treatment, and control rates remain relatively low. These findings underscore the urgent need for tailored policies to enhance hypertension management.</p><p><strong>Funding: </strong>The work was supported by the National Health Commission of the People's Republic of China and Major Science and Technology Special Plan Project of Yunnan Province.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100808"},"PeriodicalIF":11.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971966","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}
MedPub Date : 2025-08-19DOI: 10.1016/j.medj.2025.100806
Ridwan Alam, Jeffrey W Fuchs, Niraj K Shenoy
{"title":"Utility of circulating tumor DNA in management of diverse renal malignancies: Insights from a case series in adjuvant and recurrent/metastatic settings.","authors":"Ridwan Alam, Jeffrey W Fuchs, Niraj K Shenoy","doi":"10.1016/j.medj.2025.100806","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100806","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumor DNA (ctDNA) monitoring offers a minimally invasive method for detecting molecular residual disease and assessing treatment response. While increasingly adopted in several cancers, its clinical utility in renal malignancies remains underexplored, primarily due to low ctDNA shedding in kidney cancers.</p><p><strong>Methods: </strong>We present a case series of six patients with diverse renal malignancies (clear cell renal cell carcinoma [ccRCC], papillary RCC, translocation RCC, malignant angiomyolipoma, and squamous cell carcinoma of the renal pelvis) managed in both adjuvant and recurrent/metastatic settings. All patients underwent serial ctDNA testing using the Signatera (exome-based) tumor-informed assay alongside conventional imaging.</p><p><strong>Findings: </strong>ctDNA results influenced clinical decisions in all six cases. In the adjuvant setting, positive ctDNA indicated molecular residual disease, prompted initiation of therapy, and allowed monitoring of treatment response and recurrence during surveillance. In recurrent/metastatic disease, ctDNA trends often preceded radiographic progression, enabling earlier intervention or treatment modification. In some instances, ctDNA provided crucial insights during imaging uncertainty or treatment breaks due to toxicity. Sustained ctDNA clearance was associated with favorable cancer-specific outcomes.</p><p><strong>Conclusions: </strong>While the lower sensitivity, limited negative predictive value, and financial burden of ctDNA monitoring in kidney cancers constitute significant limitations, a positive result can potentially serve as a highly informative adjunct to imaging-based surveillance for monitoring disease status and treatment response. This case series supports and informs future studies on ctDNA in the management of renal malignancies.</p><p><strong>Funding: </strong>ctDNA testing for these patients was supported by Natera, the manufacturer of the Signatera assay.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100806"},"PeriodicalIF":11.8,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971971","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}
MedPub Date : 2025-08-08Epub Date: 2025-05-13DOI: 10.1016/j.medj.2025.100677
Yan-Ruide Li, Yichen Zhu, Ying Fang, Zibai Lyu, Lili Yang
{"title":"Emerging trends in clinical allogeneic CAR cell therapy.","authors":"Yan-Ruide Li, Yichen Zhu, Ying Fang, Zibai Lyu, Lili Yang","doi":"10.1016/j.medj.2025.100677","DOIUrl":"10.1016/j.medj.2025.100677","url":null,"abstract":"<p><p>There has been significant progress in the clinical development of allogeneic off-the-shelf chimeric antigen receptor (CAR)-engineered cell therapies for the treatment of cancer and autoimmune diseases. Unlike autologous CAR cell therapies, allogeneic approaches overcome challenges such as high costs, labor-intensive manufacturing, and stringent patient selection. This makes allogeneic therapies a more universally applicable option for a diverse patient population. In this review, we examine recent clinical advancements in allogeneic CAR cell therapies, including CAR-T cell therapy derived from healthy donor peripheral blood mononuclear cells, as well as CAR-NK cell therapy from cord blood or induced pluripotent stem cells. We provide an overview of their genetic engineering strategies, clinical designs, and outcomes, highlighting their promising efficacy and safety. Additionally, we summarize key preclinical developments, address key challenges, and explore future directions to provide insights into emerging trends in the field.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100677"},"PeriodicalIF":11.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080957","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}