Med最新文献

{"title":"Glucagon-like peptide receptor-1 receptor agonists: The emerging fourth pillar in type 2 diabetes and chronic kidney disease?","authors":"James Ling, Elaine Chow","doi":"10.1016/j.medj.2024.06.010","DOIUrl":"10.1016/j.medj.2024.06.010","url":null,"abstract":"<p><p>Previously, no randomized controlled trials investigated the renoprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) as the primary endpoint in patients with diabetes and chronic kidney disease. In the FLOW trial, Perkovic et al. showed that once-weekly semaglutide reduced kidney failure, kidney-related death, and cardiovascular death by 24% as compared with placebo in patients with type 2 diabetes at high risk of renal progression.¹.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914217","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":"COX inhibition with anti-PD-1 in advanced dMMR colorectal cancer: Improving antigen presentation?","authors":"Benoit Rousseau, Paul Johannet","doi":"10.1016/j.medj.2024.06.009","DOIUrl":"10.1016/j.medj.2024.06.009","url":null,"abstract":"<p><p>dMMR tumors, which have high tumor mutational and neoantigen burdens, are highly responsive to immune checkpoint blockade. Wu et al.¹ showed that combining COX inhibitors with PD-1 blockade could be a safe and effective treatment option for dMMR metastatic colorectal cancer. The study highlights the potential of this combination therapy in achieving deep and long-lasting responses in dMMR colorectal cancers.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914216","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":"Storage, preservation, and rehabilitation of living heart valves to treat congenital heart disease.","authors":"Elizabeth M Cordoves, Giovanni Ferrari, Emmanuel Zorn, Emile Bacha, Gordana Vunjak-Novakovic, David M Kalfa","doi":"10.1016/j.medj.2024.07.004","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.004","url":null,"abstract":"<p><p>Heart valve disease patients undergo multiple surgeries to replace structurally degraded valve prostheses, highlighting the need for valve replacements with growth and self-repair capacity. Given allogeneic valve transplantation's promise in meeting these goals by delivering a living valve replacement, we propose a framework for preserving and rehabilitating living valves ex vivo.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914219","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":"Cellular dynamics in pig-to-human kidney xenotransplantation.","authors":"Wanqing Pan, Weimin Zhang, Binghan Zheng, Brendan R Camellato, Jeffrey Stern, Ziyan Lin, Alireza Khodadadi-Jamayran, Jacqueline Kim, Philip Sommer, Karen Khalil, Elaina Weldon, Jiangshan Bai, Yinan Zhu, Peter Meyn, Adriana Heguy, Massimo Mangiola, Adam Griesemer, Brendan J Keating, Robert A Montgomery, Bo Xia, Jef D Boeke","doi":"10.1016/j.medj.2024.05.003","DOIUrl":"10.1016/j.medj.2024.05.003","url":null,"abstract":"<p><strong>Background: </strong>Xenotransplantation of genetically engineered porcine organs has the potential to address the challenge of organ donor shortage. Two cases of porcine-to-human kidney xenotransplantation were performed, yet the physiological effects on the xenografts and the recipients' immune responses remain largely uncharacterized.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (scRNA-seq) and longitudinal RNA-seq analyses of the porcine kidneys to dissect xenotransplantation-associated cellular dynamics and xenograft-recipient interactions. We additionally performed longitudinal scRNA-seq of the peripheral blood mononuclear cells (PBMCs) to detect recipient immune responses across time.</p><p><strong>Findings: </strong>Although no hyperacute rejection signals were detected, scRNA-seq analyses of the xenografts found evidence of endothelial cell and immune response activation, indicating early signs of antibody-mediated rejection. Tracing the cells' species origin, we found human immune cell infiltration in both xenografts. Human transcripts in the longitudinal bulk RNA-seq revealed that human immune cell infiltration and the activation of interferon-gamma-induced chemokine expression occurred by 12 and 48 h post-xenotransplantation, respectively. Concordantly, longitudinal scRNA-seq of PBMCs also revealed two phases of the recipients' immune responses at 12 and 48-53 h. Lastly, we observed global expression signatures of xenotransplantation-associated kidney tissue damage in the xenografts. Surprisingly, we detected a rapid increase of proliferative cells in both xenografts, indicating the activation of the porcine tissue repair program.</p><p><strong>Conclusions: </strong>Longitudinal and single-cell transcriptomic analyses of porcine kidneys and the recipient's PBMCs revealed time-resolved cellular dynamics of xenograft-recipient interactions during xenotransplantation. These cues can be leveraged for designing gene edits and immunosuppression regimens to optimize xenotransplantation outcomes.</p><p><strong>Funding: </strong>This work was supported by NIH RM1HG009491 and DP5OD033430.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082387","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":"Opportunities and challenges for immunosuppression in the context of pig-to-human xenotransplantation.","authors":"Guillaume Onyeaghala, Casey R Dorr, Ajay K Israni","doi":"10.1016/j.medj.2024.07.017","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.017","url":null,"abstract":"<p><p>The transplantation of organ(s) across species may alleviate the shortage of available donor kidneys for an ever-growing number of patients on transplant waiting lists. However, this potential remains limited by uncharacterized physiologic and immune effects of xenotransplants in recipients, which Pan et al.¹ investigated in the current study.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914218","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":"Socioeconomic characteristics, cancer mortality, and universal health coverage: A global analysis.","authors":"Chenran Wang, Yadi Zheng, Zilin Luo, Jiaxin Xie, Xiaolu Chen, Liang Zhao, Wei Cao, Yongjie Xu, Fei Wang, Xuesi Dong, Fengwei Tan, Ni Li, Jie He","doi":"10.1016/j.medj.2024.04.002","DOIUrl":"10.1016/j.medj.2024.04.002","url":null,"abstract":"<p><strong>Background: </strong>Achieving universal health coverage (UHC) involves all individuals attaining accessible health interventions at an affordable cost. We examined current patterns and temporal trends of cancer mortality and UHC across sociodemographic index (SDI) settings, and quantified these association.</p><p><strong>Methods: </strong>We used data from the Global Burden of Disease Study 2019 and Our World in Data. The UHC effective coverage index was obtained to assess the potential population health gains delivered by health systems. The estimated annual percentage change (EAPC) with a 95% confidence interval (CI) was calculated to quantify the trend of cancer age-standardized mortality rate (ASMR). A generalized linear model was applied to estimate the association between ASMR and UHC.</p><p><strong>Findings: </strong>The high (EAPC = -0.9% [95% CI, -1.0%, -0.9%]) and high-middle (-0.9% [-1.0%, -0.8%]) SDI regions had the fastest decline in ASMR (per 100,000) for total cancers from 1990 to 2019. The overall UHC effective coverage index increased by 27.9% in the high-SDI quintile to 62.2% in the low-SDI quintile. A negative association was observed between ASMR for all-cancer (adjusted odds ratio [OR] = 0.87 [0.76, 0.99]), stomach (0.73 [0.56, 0.95]), breast (0.64 [0.52, 0.79]), cervical (0.42 [0.30, 0.60]), lip and oral cavity (0.55 [0.40, 0.75]), and nasopharynx (0.42 [0.26, 0.68]) cancers and high UHC level (the lowest as the reference).</p><p><strong>Conclusions: </strong>Our findings strengthen the evidence base for achieving UHC to improve cancer outcomes.</p><p><strong>Funding: </strong>This work is funded by the China National Natural Science Foundation and Chinese Academy of Medical Sciences Innovation Fund for Medical Science.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960104","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":"Functional modification of gut bacteria for disease diagnosis and treatment.","authors":"Bin Zheng, Mengyi Li, Tiange Zhang, Bowen Li, Qiuya Li, Qimanguli Saiding, Wei Chen, Mingming Guo, Seyoung Koo, Xiaoyuan Ji, Wei Tao","doi":"10.1016/j.medj.2024.06.003","DOIUrl":"10.1016/j.medj.2024.06.003","url":null,"abstract":"<p><p>Intestinal bacteria help keep humans healthy by regulating lipid and glucose metabolism as well as the immunological and neurological systems. Oral treatment using intestinal bacteria is limited by the high acidity of stomach fluids and the immune system's attack on foreign bacteria. Scientists have created coatings and workarounds to overcome these limitations and improve bacterial therapy. These preparations have demonstrated promising outcomes, with advances in synthetic biology and optogenetics improving their focused colonization and controlled release. Engineering bacteria preparations have become a revolutionary therapeutic approach that converts intestinal bacteria into cellular factories for medicinal chemical synthesis. The present paper discusses various aspects of engineering bacteria preparations, including wrapping materials, biomedical uses, and future developments.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535558","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":"Multisystem health comorbidity networks of metabolic dysfunction-associated steatotic liver disease.","authors":"Fangyuan Jiang, Lijuan Wang, Haochao Ying, Jing Sun, Jianhui Zhao, Ying Lu, Zilong Bian, Jie Chen, Aiping Fang, Xuehong Zhang, Susanna C Larsson, Christos S Mantzoros, Weilin Wang, Shuai Yuan, Yuan Ding, Xue Li","doi":"10.1016/j.medj.2024.07.013","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.013","url":null,"abstract":"<p><strong>Background: </strong>The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing, but its subsequent health consequences have not been thoroughly examined.</p><p><strong>Methods: </strong>A phenome-wide association study was conducted to map the associations of MASLD with 948 unique clinical outcomes among 361,021 Europeans in the UK Biobank. Disease trajectory and comorbidity analyses were applied to visualize the sequential patterns of multiple comorbidities related to the occurrence of MASLD. The associations jointly verified by observational and polygenic phenome-wide analyses were further replicated by two-sample Mendelian randomization analysis using data from the FinnGen study and international consortia.</p><p><strong>Findings: </strong>The observational and polygenic phenome-wide association study revealed the associations of MASLD with 96 intrahepatic and extrahepatic diseases, including circulatory, metabolic, genitourinary, neurological, gastrointestinal, and hematologic diseases. Sequential patterns of MASLD-related extrahepatic comorbidities were primarily found in circulatory, metabolic, and inflammatory diseases. Mendelian randomization analyses supported the causal associations between MASLD and the risk of several intrahepatic disorders, metabolic diseases, cardio-cerebrovascular disease, and ascites but found no associations with neurological diseases.</p><p><strong>Conclusions: </strong>This study elucidated multisystem comorbidities and health consequences of MASLD, contributing to the development of combination interventions targeting distinct pathways for health promotion among patients with MASLD.</p><p><strong>Funding: </strong>X.L. was funded by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (82204019) and Y.D. was funded by the Key Project of Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province (GZY-ZJ-KJ-24077) and the National Natural Science Foundation of China (82001673 and 82272860).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907819","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":"Rising incidence of obesity-related cancers among younger adults in China: A population-based analysis (2007-2021).","authors":"Chang Liu, Ying-Chao Yuan, Mo-Ning Guo, Zhong Xin, Guan-Jie Chen, Nan Ding, Jian-Peng Zheng, Bai Zang, Jin-Kui Yang","doi":"10.1016/j.medj.2024.07.012","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.012","url":null,"abstract":"<p><strong>Background: </strong>Developing countries face an \"obesity epidemic,\" particularly affecting children and younger adults. While obesity is a known risk factor for 12 types of cancer, primarily affecting older populations, its impact on younger generations is understudied.</p><p><strong>Methods: </strong>This study analyzed data from a population-based cancer registry covering 14.14 million individuals in China (2007-2021). We compared the incidence of obesity- and non-obesity-related cancers and applied an age-period-cohort model to estimate their impacts.</p><p><strong>Findings: </strong>Among 651,342 cancer cases, 48.47% were obesity related. The age-standardized incidence rates (ASRs) of the 12 obesity-related cancers increased annually by 3.6% (p < 0.001), while ASRs for non-obesity-related cancers remained stable. Obesity-related cancers surged among younger adults, with rates rising across successive generations. The annual percentage of change decreased with age, from 15.28% for ages 25-29 years to 1.55% for ages 60-64 years. The incidence rate ratio for obesity-related cancer was higher in younger generations compared to those born in 1962-1966. We predict that the ASR for obesity-related cancers will nearly double in the next decade.</p><p><strong>Conclusions: </strong>The rising incidence of obesity-related cancers among young adults poses a significant public health concern. The increasing cancer burden underscores the need for targeted interventions to address the obesity epidemic.</p><p><strong>Funding: </strong>This work was supported by the National Natural Science Foundation of China (81930019, 82341076) to J.-K.Y.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056682","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":"Unraveling the physiological and psychosocial signatures of pain by machine learning.","authors":"Noemi Gozzi, Greta Preatoni, Federico Ciotti, Michèle Hubli, Petra Schweinhardt, Armin Curt, Stanisa Raspopovic","doi":"10.1016/j.medj.2024.07.016","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.016","url":null,"abstract":"<p><strong>Background: </strong>Pain is a complex subjective experience, strongly impacting health and quality of life. Despite many attempts to find effective solutions, present treatments are generic, often unsuccessful, and present significant side effects. Designing individualized therapies requires understanding of multidimensional pain experience, considering physical and emotional aspects. Current clinical pain assessments, relying on subjective one-dimensional numeric self-reports, fail to capture this complexity.</p><p><strong>Methods: </strong>To this aim, we exploited machine learning to disentangle physiological and psychosocial components shaping the pain experience. Clinical, psychosocial, and physiological data were collected from 118 chronic pain and healthy participants undergoing 40 pain trials (4,697 trials).</p><p><strong>Findings: </strong>To understand the objective response to nociception, we classified pain from the physiological signals (accuracy >0.87), extracting the most important biomarkers. Then, using multilevel mixed-effects models, we predicted the reported pain, quantifying the mismatch between subjective level and measured physiological response. From these models, we introduced two metrics: TIP (subjective index of pain) and Φ (physiological index). These represent possible added value in the clinical process, capturing psychosocial and physiological pain dimensions, respectively. Patients with high TIP are characterized by frequent sick leave from work and increased clinical depression and anxiety, factors associated with long-term disability and poor recovery, and are indicated for alternative treatments, such as psychological ones. By contrast, patients with high Φ show strong nociceptive pain components and could benefit more from pharmacotherapy.</p><p><strong>Conclusions: </strong>TIP and Φ, explaining the multidimensionality of pain, might provide a new tool potentially leading to targeted treatments, thereby reducing the costs of inefficient generic therapies.</p><p><strong>Funding: </strong>RESC-PainSense, SNSF-MOVE-IT197271.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907821","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}