Med最新文献

{"title":"Donor composition and fiber promote strain engraftment in a randomized controlled trial of fecal microbiota transplant for ulcerative colitis.","authors":"Lasha Gogokhia, Nancy Tran, Alex Grier, Manabu Nagayama, Grace Xiang, Gabriela Funez-dePagnier, Alexa Lavergne, Caroline Ericsson, Sarah Ben Maamar, Mengrui Zhang, Robert Battat, Ellen Scherl, Dana J Lukin, Randy S Longman","doi":"10.1016/j.medj.2025.100707","DOIUrl":"10.1016/j.medj.2025.100707","url":null,"abstract":"<p><strong>Background: </strong>Fecal microbiota transplantation (FMT) is an emerging treatment for ulcerative colitis (UC), but the impact of prebiotic fiber on FMT efficacy for UC is unclear. We performed a randomized, double-blind, placebo-controlled clinical trial to examine the efficacy of FMT with and without dietary fiber supplementation in patients with UC.</p><p><strong>Methods: </strong>27 patients with mild to moderate UC were randomized to receive a single FMT or placebo with or without psyllium fiber supplementation for 8 weeks. The primary outcome was clinical response at week 8, and secondary outcomes included endoscopic improvement and clinical remission. Metagenomic sequencing of fecal DNA was analyzed to determine taxonomic profiles and donor strain engraftment.</p><p><strong>Findings: </strong>The trial was terminated early due to manufacturer discontinuation of FMT product. FMT induced clinical response, remission, and endoscopic improvement in UC patients compared to placebo (p < 0.05), but fiber did not improve clinical outcomes of FMT. Recipient microbiome composition post-FMT shifted toward donor composition in responders and non-responders, but the durability of this change was stronger in responders. Clinical response and durable change in microbiome composition following FMT was donor dependent. Strain tracking analysis also demonstrated a donor-dependent variability in the rate of successful engraftment and identified a consortium of engrafted bacteria associated with treatment response or fiber supplementation.</p><p><strong>Conclusions: </strong>Single-dose FMT demonstrated clinical efficacy for mild to moderate UC compared to placebo but revealed no benefit of fiber supplementation. These results highlight proof of concept that donor selection and prebiotic fiber can shape strain-level engraftment. This study was registered at ClinicalTrials.gov: NCT03998488.</p><p><strong>Funding: </strong>National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK128257, to R.S.L.).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100707"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity.","authors":"Jadine Scragg, Dimitrios A Koutoukidis, Carsten Dirksen, Berit Lilienthal Heitmann, Susan A Jebb","doi":"10.1016/j.medj.2025.100805","DOIUrl":"10.1016/j.medj.2025.100805","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are weight management medications, achieving up to 15%-25% weight loss in clinical trials. Given their effectiveness and potential for scalability, GLP1-RAs are a welcome treatment option for obesity. However, not everyone who could benefit may be able to afford or want to use GLP1-RAs. There are limited data on adherence beyond clinical trials or on how to optimize adjunct behavioral therapy. There is little support offered after GLP1-RA cessation, where weight regain is marked. Without increased accessibility and lower costs, the rollout of GLP1-RAs may widen inequalities. Currently, GLP1-RAs do not offer a sustainable solution to the public health pressures caused by obesity, where prevention remains crucial. To take the best advantage of GLP1-RAs, we need to deploy them in ways that are cost effective, sustainable for healthcare systems, and equitable for societies.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100805"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144972034","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-BCMA CAR-T cell therapy in relapsed/refractory chronic inflammatory demyelinating polyneuropathy.","authors":"Ming-Hao Dong, Zhi-Cheng Mei, Luo-Qi Zhou, Michael Heming, Lu-Lu Xu, Yu-Xin Liu, Xiao-Wei Pang, Yun-Hui Chu, Song-Bai Cai, Huan Ye, Ke Shang, Jun Xiao, Gerd Meyer Zu Hörste, Wei Wang, Chuan Qin, Dai-Shi Tian","doi":"10.1016/j.medj.2025.100704","DOIUrl":"10.1016/j.medj.2025.100704","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammatory demyelinating polyneuropathy (CIDP) presents a significant therapeutic challenge, with up to 15% of patients being refractory to first-line treatments.</p><p><strong>Methods: </strong>Anti-B cell maturation antigen chimeric antigen receptor T (CAR-T) cell therapy was applied to two patients with highly relapsed and refractory CIDP, followed by safety and efficacy evaluation. Multi-omics analyses were performed on samples of peripheral blood mononuclear cells (PBMCs) collected before and after infusion.</p><p><strong>Findings: </strong>Both patients had no severe adverse events and achieved drug-free remission within 6 months post-CAR-T therapy. Patient 1 experienced disease recurrence 12 months post infusion following a severe infection of COVID-19, while patient 2 maintained remission over 24 months. Relapse was accompanied by reactivation of pathogenic B cells and recurrence of autoantibodies/peptides targeting axons or myelin. Metabolic reprogramming of B cells characterized by overglycolysis was linked to disease relapse, which could be modulated by regulatory factor X5.</p><p><strong>Conclusion: </strong>This study demonstrates the safety and potential of anti-BCMA CAR-T cell therapy in treating refractory CIDP and provides insights into the molecular mechanisms underlying patient responses (ClinicalTrials.gov: NCT04561557).</p><p><strong>Funding: </strong>Ministry of Science and Technology China Brain Initiative grant STI2030-Major Projects 2022ZD0204700 (to W.W.), National Natural Science Foundation of China grants 82371404 and 82071380 (to D.-S.T.) and 82471353 and 82271341 (to C.Q.), Knowledge Innovation Program of Wuhan Shuguang Project 2022020801020454 (to C.Q.), and Key Research and Development Program of Hubei Provincial Department of Science and Technology 2023BCB148 (to D.-S.T.). The clinical trial was funded by Nanjing IASO Biotechnology Co., Ltd.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100704"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162444","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":"Current paradigm of EGFR^ins20 in non-small cell lung cancer: A long way forward.","authors":"Beatriz Viesser Miyamura, Isa Mambetsariev, Jeremy Fricke, Javier Arias-Romero, Karla Cadman, Sagun Shrestha, Evan Pisick, Danny Nguyen, Jyoti Malhotra, Amanda Reyes, Ravi Salgia","doi":"10.1016/j.medj.2025.100803","DOIUrl":"10.1016/j.medj.2025.100803","url":null,"abstract":"<p><p>EGFR^ins20 alterations are detected in 5% to 12% of the EGFR mutated subgroup in advanced non-small cell lung cancer. Historically, these alterations have been correlated with worse prognosis among the common EGFR mutation subtypes, which largely respond only to chemotherapy. The availability of new targeted therapies with EGFR^ins20 activity has transformed the precision medicine landscape for patients, with improved outcomes and survival. Previous clinical trials evaluating EGFR holistic targeted therapies, such as erlotinib, gefitinib, and osimertinib, in EGFR^ins20 patients have all failed, requiring a realignment of EGFR^ins20 therapeutic drug development. New clinical trial data on EGFR^ins20-specific targeted therapies have led to US Food and Drug Administration (FDA) approval of amivantamab-vmjw and accelerated FDA approval of sunvozertinib, with more clinical trial drugs currently under investigation. Next-generation sequencing (NGS) testing, including liquid biopsy, should be prioritized to differentiate patients with this subtype and consider the individual EGFR^ins20 variants that may respond differently to available therapeutics.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100803"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting BCMA in CIDP: Valuable insights gained through multi-omics immune monitoring.","authors":"Maximilian A Funk, Sebastian Theurich","doi":"10.1016/j.medj.2025.100753","DOIUrl":"10.1016/j.medj.2025.100753","url":null,"abstract":"<p><p>Dong et al. present two patients with refractory chronic inflammatory demyelinating polyneuropathy (CIDP), who received treatment with B-cell-maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cells.¹ Extensive concomitant immune monitoring provides insights into the pathogenesis and mechanisms of relapse in CIDP that may help to determine the role of BCMA-targeted CAR-T cell therapy for this disease in the future.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 9","pages":"100753"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058650","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":"A metabolic syndrome: Understanding host factors that drive mortality in tuberculosis meningitis.","authors":"Jeffrey M Collins, Russell R Kempker","doi":"10.1016/j.medj.2025.100705","DOIUrl":"10.1016/j.medj.2025.100705","url":null,"abstract":"<p><p>Cerebrospinal fluid metabolomics uncovered distinct short chain fatty acids and amino acids strongly associated with mortality in persons with tuberculosis meningitis (TBM). These findings from Nhat et al. highlight the critical role of energy metabolism in the host response to TBM and provide new avenues to explore and target for host-directed therapy.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 9","pages":"100705"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058694","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":"Oral lamivudine in diabetic macular edema: A randomized, double-blind, placebo-controlled clinical trial.","authors":"Felipe Pereira, Joseph Magagnoli, Meenakshi Ambati, Talita Fernandes de Oliveira, Juliana Angélica Estevão de Oliveira, Vinicius Oliveira Pesquero, Lucas Zago Ribeiro, Dante Akira Kondo Kuroiwa, Fernando Korn Malerbi, Sergio Atala Dib, Nilva Bueno Moraes, Michel Eid Farah, Eduardo Buchele Rodrigues, Jayakrishna Ambati","doi":"10.1016/j.medj.2025.100747","DOIUrl":"10.1016/j.medj.2025.100747","url":null,"abstract":"<p><strong>Background: </strong>Diabetic macular edema (DME) affects millions worldwide. Intraocular injections of expensive anti-vascular endothelial growth factor (VEGF) inhibitors associated with complications are standard therapy. Lamivudine, an inexpensive oral drug, inhibits inflammasome activation, which is implicated in DME. This randomized, double-blind, placebo-controlled trial compared oral lamivudine to placebo for improving visual acuity in center-involved DME (CI-DME).</p><p><strong>Methods: </strong>Twenty-four adults enrolled between February 2022 and September 2023 with 1 or 2 eyes with CI-DME and a best-corrected visual acuity (BCVA) of less than 69 letters (Brazilian Registry of Clinical Trials RBR-87b6r5s) were randomized to lamivudine (150 mg twice daily; 10 participants; 16 eyes) or placebo (14 participants; 21 eyes) for 8 weeks. Participants were assigned intravitreous bevacizumab (1.25 mg) at week 4. Co-primary outcomes were mean changes in BCVA from baseline to weeks 4 and 8. Comparisons to anti-VEGF drugs used synthetic controls from DRCR.net Protocol T. Secondary outcomes included retinal thickness and adverse events.</p><p><strong>Findings: </strong>At 4 weeks, BCVA improved 9.8 letters with lamivudine and decreased 1.8 letters with placebo (p < 0.001). At 8 weeks, BCVA improved 16.9 letters with lamivudine and bevacizumab and 5.3 letters with placebo and bevacizumab (p < 0.001). Lamivudine was associated with greater BCVA improvement than bevacizumab or ranibizumab (p < 0.05) and was not different from aflibercept (p = 0.5). There was no significant difference in retinal thickness or adverse events between groups.</p><p><strong>Conclusions: </strong>Lamivudine, an oral inflammasome inhibitor, significantly improved vision in patients with CI-DME.</p><p><strong>Funding: </strong>This work was supported by Universidade Federal de São Paulo, Latinofarma, UVA SIF, and NIH.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100747"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of adjuvant TTFields plus pembrolizumab and temozolomide in newly diagnosed glioblastoma: A phase 2 study.","authors":"Dongjiang Chen, Son B Le, Ashley P Ghiaseddin, Harshit Manektalia, Ming Li, Adam O'Dell, Maryam Rahman, David D Tran","doi":"10.1016/j.medj.2025.100708","DOIUrl":"10.1016/j.medj.2025.100708","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have shown limited success in glioblastoma due to the tumor's profoundly immunosuppressive microenvironment. Tumor treating fields (TTFields), a non-invasive electric field therapy, activate the type I interferon (T1IFN) pathway via DNA sensor-dependent inflammasomes, promoting in situ immunization against glioblastoma.</p><p><strong>Methods: </strong>In this phase 2 study (this study was registered at ClinicalTrials.gov: NCT03405792), 31 newly diagnosed glioblastoma patients were enrolled post-chemoradiation to evaluate synergy between TTFields, pembrolizumab, and temozolomide. The primary endpoint was progression-free survival (PFS) compared to case-matched controls treated with TTFields and temozolomide alone. Secondary endpoints included overall survival (OS), response rate, safety, and immune correlates assessed through single-cell transcriptomics and T cell clonotyping of blood and tumor samples.</p><p><strong>Findings: </strong>Among 26 patients treated per protocol, the median PFS was 12.0 vs. 5.8 months in controls (HR 0.377, 95% CI 0.217-0.653; p = 0.0026), and the median OS was 24.8 vs. 14.6 months (HR 0.522, 95% CI 0.301-0.905; p = 0.0477). Patients undergoing biopsy had longer PFS (27.2 vs. 9.6 months; HR 0.37, 95% CI 0.16-0.85; p = 0.014) and OS (31.6 vs. 18.8 months; HR 0.4, 95% CI 0.17-0.92; p = 0.023) compared to maximal resection. Severe adverse events constituted 7.5% of treatment-related toxicities. TTFields promoted clonal T cell expansion via a T1IFN-driven trajectory, while pembrolizumab supported adaptive replacement of these clones, sustaining T cell activation and memory formation, especially in biopsy-only patients.</p><p><strong>Conclusions: </strong>These findings demonstrate synergy between TTFields and ICIs, particularly in patients with high tumor burden, and support further study in larger trials.</p><p><strong>Funding: </strong>This work was supported by a grant from Novocure.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100708"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226942","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":"Longitudinal progression of blood biomarkers reveals a key role of reactive astrocytosis in preclinical Alzheimer's disease.","authors":"Vijay R Varma, Yang An, Przemek R Kac, Murat Bilgel, Abhay Moghekar, Tina Loeffler, David Amschl, Magdalena Daurer, Manuela Prokesch, Juan Troncoso, Kaj Blennow, Henrik Zetterberg, Nicholas J Ashton, Luigi Ferrucci, Susan M Resnick, Madhav Thambisetty","doi":"10.1016/j.medj.2025.100724","DOIUrl":"10.1016/j.medj.2025.100724","url":null,"abstract":"<p><strong>Background: </strong>Defining the progression of blood biomarkers in Alzheimer's disease (AD) is essential for targeting treatments in patients most likely to benefit from early intervention. We delineated the temporal ordering of blood biomarkers a decade prior to the onset of AD, explored associations with AD brain pathology, and examined the relationship between reactive astrocytosis in the brain and plasma in a transgenic mouse model.</p><p><strong>Methods: </strong>We analyzed plasma blood biomarkers using the Quanterix HD-X instrument in case-control and postmortem cohorts from the Baltimore Longitudinal Study on Aging (BLSA). We assessed plasma and cortical reactive astrocytosis, measured by glial fibrillary acidic protein (GFAP), in 5xFAD transgenic and wild-type mice.</p><p><strong>Findings: </strong>In AD-converters (N = 158, 377 samples), higher plasma GFAP levels are observed 10 years prior to the onset of cognitive impairment due to AD compared with individuals who remain cognitively unimpaired (N = 160, 379 samples). Plasma GFAP levels are highest in neuropathologically confirmed AD, intermediate in asymptomatic AD, and lowest in cognitively unimpaired and associated with severity of neuritic plaques and neurofibrillary tangles. GFAP-labeled immunoreactive astrocytes in the cortex of 3- and 7-month-old 5xFAD transgenic mice increased relative to wild-type mice and higher blood GFAP concentration was associated with more GFAP-expressing astrocytes.</p><p><strong>Conclusions: </strong>Reactive astrocytosis, assessed by elevated GFAP levels, is an early event in the progression of blood biomarker changes in preclinical AD, may be an early marker of AD pathogenesis, and a promising therapeutic target.</p><p><strong>Funding: </strong>Intramural Research Program, NIA.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100724"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267481","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":"Recognizing overweight and obesity as chronic diseases and acknowledging root causes.","authors":"Bryn E Falahee, Dong Wook Kim, Caroline M Apovian","doi":"10.1016/j.medj.2025.100782","DOIUrl":"10.1016/j.medj.2025.100782","url":null,"abstract":"<p><p>As obesity increases in the global population, it is important to recognize that obesity is not a willpower failure but a chronic disease regulated by genetic, environmental, and hormonal control of energy balance. Obesity is also caused by social and political factors, including poor regulation of the food industry and lack of access to healthy, affordable foods. To de-stigmatize obesity, we need to understand and teach the pathophysiology of overweight and obesity in the same way we teach the pathophysiology of cardiovascular disease or type 2 diabetes. The controversy surrounding the need for new incretin-mimetic obesity medications illustrates the lack of understanding of obesity as a chronic disease. While we may not be able to change social conditions, modify genetic or environmental factors, or regulate the food industry, we can de-stigmatize obesity and overweight in our clinics and offer appropriate treatment.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100782"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754644","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}