Med最新文献

{"title":"Clinical trials reimagined: Integrating community engagement and artificial intelligence.","authors":"Isla S Mackenzie, LaPrincess C Brewer, Alex Zhavoronkov","doi":"10.1016/j.medj.2025.100743","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100743","url":null,"abstract":"<p><p>In celebration of Clinical Trials Day, May 20, this collection of Voices highlights visionary perspectives on the evolving landscape of clinical research. It explores decentralized clinical trials, which bring research into participants' homes, enhancing diversity and convenience. It also emphasizes the imperative of community engagement to address health disparities and build trust. Finally, it showcases how generative AI promises to revolutionize drug discovery and clinical development through end-to-end automation and precision. Together, these insights underscore transformative shifts where innovation, inclusivity, and technology converge to accelerate the delivery of effective therapies for all.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 6","pages":"100743"},"PeriodicalIF":12.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295067","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":"WAYPOINT: Are we there yet for patients with nasal polyposis?","authors":"Jack L Birkenbeuel, Vinay K Rathi","doi":"10.1016/j.medj.2025.100701","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100701","url":null,"abstract":"<p><p>The WAYPOINT trial demonstrated that tezepelumab treatment for chronic sinusitis with nasal polyposis was associated with statistically significant and clinically meaningful reductions vs. placebo in both objective (nasal polyp score and rates of rescue steroids or surgery) and subjective (nasal congestion, loss of smell, and sinonasal outcomes test scores) measures of disease burden at 52 weeks.¹.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 6","pages":"100701"},"PeriodicalIF":12.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295074","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":"Allogeneic CD19-targeted CAR-T therapy in refractory systemic lupus erythematosus achieved durable remission.","authors":"Dandan Wang, Xiaobing Wang, Binghe Tan, Xin Wen, Songying Ye, Yingyi Wu, Xuan Cao, Xin Zhang, Chun Wang, Linyu Geng, Huayong Zhang, Xuebing Feng, Biao Zheng, Yanran He, Mingyao Liu, Xin Wu, Bing Du, Lingyun Sun, Huji Xu","doi":"10.1016/j.medj.2025.100749","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100749","url":null,"abstract":"<p><strong>Background: </strong>Autoreactive B cells play a key role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study is to assess the safety of allogeneic chimeric antigen receptor (CAR)-T cells for patients with lupus. This study was registered at ClinicalTrials.gov (NCT05859997).</p><p><strong>Methods: </strong>In this study, 3 patients with refractory and severe SLE with multi-organ involvement were enrolled. Genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells were infused intravenously at a dose of 1 million cells per kilogram of body weight. The safety indices, including the occurrence of graft-versus-host disease (GvHD), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS), were evaluated. The proliferation of CAR+ T cells and the number of peripheral B cells were assessed. The clinical efficacy was also assessed based on the SELENA-SLEDAI, SLEDAI-2K, BILAG, clinical SLE responder index-4 (SRI-4), and DORIS remission index.</p><p><strong>Findings: </strong>Between August 2023 and October 2023, 3 patients with SLE were enrolled and completed a 12-month follow-up. No patient underwent GvHD, CRS, or ICANS, and no severe adverse events were recorded. CAR+ T cells expanded in vivo, peaking at day 14, and then declined. The percentage of B cells in lymphocytes and the absolute circulating B cell counts were profoundly decreased. Patient 1 withdrew from the study at month 1 due to unresolved and severe thrombocytopenia and the need for the addition of an immunosuppressive drug. SELENA-SLEDAI and SLEDAI-2K scores declined, and all the patients reached SRI-4 remission at the last visit.</p><p><strong>Conclusions: </strong>In patients with severe and refractory SLE, allogeneic CAR-T cell therapy showed profound safety and clinical efficacy for disease remission.</p><p><strong>Funding: </strong>82320108010, 31821003, 81930043, 82330055, and U24A20380.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100749"},"PeriodicalIF":12.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188175","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":"Epidural electrical stimulation facilitates motor recovery in spinal cord injury involving the conus medullaris: A case study.","authors":"Luigi Albano, Daniele Emedoli, Filippo Agnesi, Simone Romeni, Elena Losanno, Laura Toni, Veronica Fossati, Chiara Ciucci, Filippo Gasperotti, Leonardo Cociani, Giovanni Zucco, Edoardo Pompeo, Cinzia Mura, Jacopo Carpaneto, Andrea Tettamanti, Veronica Castelnovo, Jeffrey David Padul, Carlo Mandelli, Lina Raffaella Barzaghi, Federica Alemanno, Heike Caravati, Carla Butera, Ubaldo Del Carro, Antonella Castellano, Andrea Falini, Federica Agosta, Massimo Filippi, Sandro Iannaccone, Pietro Mortini, Silvestro Micera","doi":"10.1016/j.medj.2025.100706","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100706","url":null,"abstract":"<p><strong>Background: </strong>Emerging research increasingly supports that epidural spinal cord electrical stimulation (EES) combined with neurorehabilitation can improve motor recovery in spinal cord injury (SCI) subjects. Patients with lesions involving the medullary cone may be challenging to treat with this approach, probably due to potential peripheral nervous system damage, leaving the open question of whether this large population may benefit from EES.</p><p><strong>Methods: </strong>A T11-T12 SCI patient, with medullary cone involvement, underwent EES implant in a clinical trial (NCT05926843). During three months of testing, we determined optimal stimulation protocols for improving isolated movements and integrated them to reinstate independent walking with a walker.</p><p><strong>Findings: </strong>EES substantially boosted hip flexor, spinal erector, and abdominal muscle contraction, improving the patient's performance in isolated movements. Over three months of combining continuous subthreshold EES with personalized rehabilitation, the patient progressed from being unable to walk to overground ambulation using a two-wheeled walker and bilateral knee and foot orthoses. At the time of hospital discharge, the patient managed to cover 58 m in the 6-min walking test and completed the 10-meter walking test in 40.29 s. Six months after EES implant, the patient was able to walk independently for 1 km with a walker.</p><p><strong>Conclusions: </strong>These results underscore the potential of neurorehabilitation protocols integrating EES also for patients with medullary cone lesions and pave the way for new rehabilitation prospects.</p><p><strong>Funding: </strong>This work was funded by Università Vita-Salute San Raffaele, Boston Scientific Spa, Fondazione Cariplo, Bertarelli Foundation, and the Ministry of University and Research (MUR).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100706"},"PeriodicalIF":12.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175106","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":"Inactivation of TACC2 epigenetically represses CDKN1A and confers sensitivity to CDK inhibitors.","authors":"Zhi-Rui Lin, Tian-Liang Xia, Meng-Yao Wang, Lan-Jun Zhang, Yan-Min Liu, Bo-Yu Yuan, Ai-Jun Zhou, Li Yuan, Jian Zheng, Jin-Xin Bei, Dong-Xin Lin, Mu-Sheng Zeng, Qian Zhong","doi":"10.1016/j.medj.2024.12.002","DOIUrl":"10.1016/j.medj.2024.12.002","url":null,"abstract":"<p><strong>Background: </strong>The genomic landscape of esophageal squamous cell carcinoma (ESCC) has been characterized extensively, but there remains a significant need for actionable targets and effective therapies.</p><p><strong>Methods: </strong>Here, we perform integrative analysis of genome-wide loss of heterozygosity and expression to identify potential tumor suppressor genes. The functions and mechanisms of one of the candidates, TACC2, are then explored both in vitro and in vivo, leading to the proposal of a therapeutic strategy based on the concept of synthetic lethality.</p><p><strong>Findings: </strong>We reveal that the inactivation of TACC2, due to copy number loss and promoter hypermethylation, is associated with poor prognosis in ESCC patients. TACC2 depletion enhances ESCC tumorigenesis and progression, as demonstrated in Tacc2 knockout mouse models and by increased growth abilities of ESCC cells. Mechanistically, TACC2 interacts with components of the NuRD and CoREST co-repressor complexes, including MTA1, MBD3, and HMG20B, in the cytoplasm. TACC2 loss leads to the translocation of these proteins into the nucleus, facilitating the formation of functional NuRD and CoREST complexes and the epigenetic repression of CDKN1A. This repression results in elevated CDK1/2 activation. Furthermore, TACC2-deficient cells and ESCC patient-derived organoids with reduced TACC2 expression show increased sensitivity to CDK inhibitors, particularly dinaciclib, which is currently in a phase III trial. Notably, the combination of TACC2-specific RNAi and dinaciclib in subcutaneous ESCC models significantly impairs tumor growth.</p><p><strong>Conclusions: </strong>The findings suggest a strategy for cancer treatment based on synthetic lethality.</p><p><strong>Funding: </strong>Funded by NKRDP, NSFC, GDIIET, GDBABRF, GDECISTP, and SYSUTP.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100568"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967017","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":"Regulatory T cell therapy is associated with distinct immune regulatory lymphocytic infiltrates in kidney transplants.","authors":"Oliver McCallion, Amy R Cross, Matthew O Brook, Conor Hennessy, Ricardo Ferreira, Dominik Trzupek, William R Mulley, Sandeep Kumar, Maria Soares, Ian S Roberts, Peter J Friend, Giovanna Lombardi, Kathryn J Wood, Paul N Harden, Joanna Hester, Fadi Issa","doi":"10.1016/j.medj.2024.11.014","DOIUrl":"10.1016/j.medj.2024.11.014","url":null,"abstract":"<p><strong>Background: </strong>Adoptive transfer of autologous regulatory T cells (Tregs) is a promising therapeutic strategy aimed at enabling immunosuppression minimization following kidney transplantation. In our phase 1 clinical trial of Treg therapy in living donor renal transplantation, the ONE Study (ClinicalTrials.gov: NCT02129881), we observed focal lymphocytic infiltrates in protocol kidney transplant biopsies that are not regularly seen in biopsies of patients receiving standard immunosuppression.</p><p><strong>Methods: </strong>We present 7 years of follow-up data on patients treated with adoptive Treg therapy early post-transplantation who exhibited focal lymphocytic infiltrates on a 9-month protocol biopsy. We phenotyped their adoptively transferred and peripherally circulating Treg compartments using CITE-seq and investigated the focal lymphocytic infiltrates with spatial proteomic and transcriptomic technologies.</p><p><strong>Findings: </strong>Graft survival rates were not significantly different between Treg-treated patients and the control reference group. None of the Treg-treated patients experienced clinical rejection episodes or developed de novo donor-specific antibodies, and three of ten successfully reduced their immunosuppression to tacrolimus monotherapy. All Treg-treated patients who underwent a protocol biopsy 9 months post-transplantation exhibited focal lymphocytic infiltrates. Spatial profiling analysis revealed prominent CD20⁺ B cell and regulatory (IKZF2, IL10, PD-L1, TIGIT) signatures within cell-therapy-associated immune infiltrates, distinct from the pro-inflammatory myeloid signature associated with rejection biopsies.</p><p><strong>Conclusions: </strong>We demonstrate for the first time that immune cell infiltrates in transplanted kidneys can occur following adoptive Treg therapy in humans, potentially facilitating within-graft T:B cell interactions that promote local immune regulation.</p><p><strong>Funding: </strong>This work was funded by the 7^th EU Framework Programme, grant/award no. 260687, and the National Institute for Health Research (NIHR).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100561"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898728","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":"ElevateHER: Engineering a new era in women's health.","authors":"Erika Moore, Shreya A Raghavan","doi":"10.1016/j.medj.2025.100697","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100697","url":null,"abstract":"<p><p>Women's health operates in fragmented silos despite encompassing all unique biological and physiological factors affecting women across their lifespan. Consequently, healthcare decisions and technological advances take place under a universal approach, leading to data deficiency and lack of robust models to predict or tailor care for women's health. Engineering innovations hold immense potential to revolutionize health but require broader awareness of their relevance to the spectrum of challenges that fall under the umbrella of women's health. The ElevateHER (Engineering Innovations in Women's Health Discovery) conference convened scientists to identify critical areas for strategic research investment in women's health. Calls for action additionally focused on resource sharing and standardization, streamlining funding opportunities, science communication and outreach, and future workforce development. This perspective highlights these calls for action to engineer a new era in women's health with a cohesive approach that seamlessly integrates women's health into the fabric of overall health.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 5","pages":"100697"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064877","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":"The impact of real-world evidence in implementing and optimizing Alzheimer's disease care.","authors":"Harald Hampel, Gang Li, Michelle M Mielke, James E Galvin, Miia Kivipelto, Emiliano Santarnecchi, Claudio Babiloni, Viswanath Devanarayan, Rifky Tkatch, Yan Hu, Ricky Kurzman, Min Cho, Jo Vandercappellen, Yosuke Nakamura, Joanne Bell, Soeren Mattke, Nicola Toschi","doi":"10.1016/j.medj.2025.100695","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100695","url":null,"abstract":"<p><p>Real-world evidence (RWE) can complement clinical trials by addressing gaps in how approved anti-amyloid therapies for early Alzheimer's disease (AD) are used in everyday practice. This article outlines strategies to generate RWE that bridge three key challenges in AD care: low detection rates of mild cognitive impairment (MCI), limited data on long-term safety and effectiveness, and a lack of personalized treatment strategies. With MCI detection rates among primary care providers as low as 6%-15%, we propose cost-effective triage tools using electronic health records to enhance early diagnosis and intervention. We also highlight the importance of understanding anti-amyloid therapy outcomes in diverse, real-world populations. Supported by FDA initiatives, pragmatic trials and observational studies using real-world data (RWD) can help develop predictive models that incorporate biomarkers and support precision medicine. These approaches aim to move AD care beyond one-size-fits-all treatment, guiding more tailored, effective strategies for patients.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 5","pages":"100695"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045544","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":"Depemokimab in chronic rhinosinusitis with nasal polyps: A turning point or a missed opportunity?","authors":"Enrico Heffler, Giovanni Paoletti","doi":"10.1016/j.medj.2025.100674","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100674","url":null,"abstract":"<p><p>The ANCHOR-1 and ANCHOR-2 trials of the long-acting anti-interleukin (IL)-5 monoclonal antibody depemokibab in chronic rhinosinusitis with nasal polyposis demonstrated the safety and statistical efficacy of the drug compared to placebo.¹ However, its clinical benefits appear limited compared to other biologic therapies. The reduced dosing interval may improve adherence, but further research is needed to identify the most responsive patients.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 5","pages":"100674"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988116","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":"Bioengineering solutions to improve women's health.","authors":"Catherine M Klapperich, Gordana Vunjak-Novakovic, Jenny Robinson, Renita Horton, Pamela K Kreeger, Morteza Mahmoudi, Samit Shah, Antonina Frolova","doi":"10.1016/j.medj.2025.100699","DOIUrl":"10.1016/j.medj.2025.100699","url":null,"abstract":"<p><p>In recognition of The International Day of Action for Women's Health on May 28^th, we bring together a collection of Voices highlighting the need for innovative solutions to tackle long-standing women's health challenges from a bioengineering perspective. Many common diseases manifest differently in women, and an insufficient understanding of the underlying mechanisms as well as a lack of tailored treatment strategies continue to impact health outcomes. Bioengineered organoids, organ-on-chip systems, and biomaterials hold promise as tools to dissect pathological mechanisms in reproductive health, cancer, autoimmune diseases, and musculoskeletal health, while tailored diagnostic and therapeutic strategies can enhance the efficacy of clinical interventions. An interdisciplinary approach uniting technological, translational, and clinical research is essential to realize the full potential of bioengineering solutions to improve women's health.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 5","pages":"100699"},"PeriodicalIF":12.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001035","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}