Nature Medicine最新文献

{"title":"Sustained effect of prasinezumab on Parkinson’s disease motor progression in the open-label extension of the PASADENA trial","authors":"Gennaro Pagano, Annabelle Monnet, Adriana Reyes, Benjamin Ribba, Hanno Svoboda, Thomas Kustermann, Tanya Simuni, Ronald B. Postuma, Nicola Pavese, Fabrizio Stocchi, Kathrin Brockmann, Krzysztof Smigorski, Valentina Gerbaldo, Paulo Fontoura, Rachelle Doody, Geoffrey A. Kerchner, Patrik Brundin, Kenneth Marek, Azad Bonni, Tania Nikolcheva","doi":"10.1038/s41591-024-03270-6","DOIUrl":"https://doi.org/10.1038/s41591-024-03270-6","url":null,"abstract":"<p>The Phase II trial of Anti-alpha-Synuclein Antibody in Early Parkinson’s Disease (PASADENA) is an ongoing double-blind, placebo-controlled trial evaluating the safety and efficacy of prasinezumab in early-stage Parkinson’s disease (PD). During the double-blind period, prasinezumab-treated individuals showed less progression of motor signs (Movement Disorders Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS–UPDRS) Part III) than placebo-treated individuals. We evaluated whether the effect of prasinezumab on motor progression, assessed as a change in MDS–UPDRS Part III score in the OFF and ON states, and MDS–UPDRS Part II score, was sustained for 4 years from the start of the trial. We compared participants enrolled in the PASADENA open-label extension study with those enrolled in an external comparator arm derived from the Parkinson’s Progression Markers Initiative observational study. The PASADENA delayed-start (<i>n</i> = 94) and early-start (<i>n</i> = 177) groups showed a slower decline (a smaller increase in score) in MDS–UPDRS Part III scores in the OFF state (delayed start, −51%; early start, −65%), ON state (delayed start, −94%; early start, −118%) and MDS–UPDRS Part II (delayed start, −48%; early start, −40%) than did the Parkinson’s Progression Markers Initiative external comparator (<i>n</i> = 303). This exploratory analysis, which requires confirmation in future studies, suggested that the effect of prasinezumab in slowing motor progression in PD may be sustained long term. PASADENA ClinicalTrials.gov no. NCT03100149.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial","authors":"Jennifer M. Mitchell, Marcela Ot’alora G, Bessel van der Kolk, Scott Shannon, Michael Bogenschutz, Yevgeniy Gelfand, Casey Paleos, Christopher R. Nicholas, Sylvestre Quevedo, Brooke Balliett, Scott Hamilton, Michael Mithoefer, Sarah Kleiman, Kelly Parker-Guilbert, Keren Tzarfaty, Charlotte Harrison, Alberdina de Boer, Rick Doblin, Berra Yazar-Klosinski","doi":"10.1038/s41591-024-03331-w","DOIUrl":"https://doi.org/10.1038/s41591-024-03331-w","url":null,"abstract":"<p>Correction to: <i>Nature Medicine</i> https://doi.org/10.1038/s41591-023-02565-4, published online 14 September 2023.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use and misuse of ‘biological aging’ in health research","authors":"M. Arfan Ikram","doi":"10.1038/s41591-024-03297-9","DOIUrl":"https://doi.org/10.1038/s41591-024-03297-9","url":null,"abstract":"Biological aging clocks are flawed concepts in understanding disease.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PROTAC protein degraders to drug the undruggable enter phase 3 trials","authors":"","doi":"10.1038/d41591-024-00072-8","DOIUrl":"https://doi.org/10.1038/d41591-024-00072-8","url":null,"abstract":"Pharmaceutical companies are investing in therapies that target proteins for degradation, with trials ongoing for cancer, autoimmune diseases and neurological disorders.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Digital consults in heart failure care: a randomized controlled trial","authors":"Jelle P. Man,&nbsp;Maarten A. C. Koole,&nbsp;Paola G. Meregalli,&nbsp;M. Louis Handoko,&nbsp;Susan Stienen,&nbsp;Frederik J. de Lange,&nbsp;Michiel M. Winter,&nbsp;Marlies P. Schijven,&nbsp;Wouter E. M. Kok,&nbsp;Dorianne I. Kuipers,&nbsp;Pim van der Harst,&nbsp;Folkert W. Asselbergs,&nbsp;Aeilko H. Zwinderman,&nbsp;Marcel G. W. Dijkgraaf,&nbsp;Steven A. J. Chamuleau,&nbsp;Mark J. Schuuring","doi":"10.1038/s41591-024-03322-x","DOIUrl":"10.1038/s41591-024-03322-x","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":58.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41591-024-03322-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive, microbiome-based diagnosis of inflammatory bowel disease","authors":"Jiaying Zheng, Qianru Sun, Mengjing Zhang, Chengyu Liu, Qi Su, Lin Zhang, Zhilu Xu, Wenqi Lu, Jessica Ching, Whitney Tang, Chun Pan Cheung, Amy L. Hamilton, Amy L. Wilson O’Brien, Shu Chen Wei, Charles N. Bernstein, David T. Rubin, Eugene B. Chang, Mark Morrison, Michael A. Kamm, Francis K. L. Chan, Jingwan Zhang, Siew C. Ng","doi":"10.1038/s41591-024-03280-4","DOIUrl":"https://doi.org/10.1038/s41591-024-03280-4","url":null,"abstract":"<p>Despite recent progress in our understanding of the association between the gut microbiome and inflammatory bowel disease (IBD), the role of microbiome biomarkers in IBD diagnosis remains underexplored. Here we developed a microbiome-based diagnostic test for IBD. By utilization of metagenomic data from 5,979 fecal samples with and without IBD from different geographies and ethnicities, we identified microbiota alterations in IBD and selected ten and nine bacterial species for construction of diagnostic models for ulcerative colitis and Crohn’s disease, respectively. These diagnostic models achieved areas under the curve &gt;0.90 for distinguishing IBD from controls in the discovery cohort, and maintained satisfactory performance in transethnic validation cohorts from eight populations. We further developed a multiplex droplet digital polymerase chain reaction test targeting selected IBD-associated bacterial species, and models based on this test showed numerically higher performance than fecal calprotectin in discriminating ulcerative colitis and Crohn’s disease from controls. Here we discovered universal IBD-associated bacteria and show the potential applicability of a multibacteria biomarker panel as a noninvasive tool for IBD diagnosis.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome","authors":"Victoria T. Chu, Abigail Glascock, Deborah Donnell, Cole Grabow, Clare E. Brown, Ryan Ward, Christina Love, Katrina L. Kalantar, Stephanie E. Cohen, Chase Cannon, Michael H. Woodworth, Colleen F. Kelley, Connie Celum, Anne F. Luetkemeyer, Charles R. Langelier","doi":"10.1038/s41591-024-03274-2","DOIUrl":"https://doi.org/10.1038/s41591-024-03274-2","url":null,"abstract":"&lt;p&gt;Doxycycline post-exposure prophylaxis (doxy-PEP) reduces bacterial sexually transmitted infections among men who have sex with men and transgender women. Although poised for widespread clinical implementation, the impact of doxy-PEP on antimicrobial resistance remains a primary concern as its effects on the gut microbiome and resistome, or the antimicrobial resistance genes (ARGs) present in the gut microbiome, are unknown. To investigate these effects, we studied participants from the DoxyPEP trial, a randomized clinical trial comparing doxy-PEP use, a one-time doxycycline 200-mg dose taken after condomless sex (DP arm, &lt;i&gt;n&lt;/i&gt; = 100), to standard of care (SOC arm, &lt;i&gt;n&lt;/i&gt; = 50) among men who have sex with men and transgender women. From self-collected rectal swabs at enrollment (day-0) and after 6 months (month-6), we performed metagenomic DNA sequencing (DNA-seq) or metatranscriptomic RNA sequencing (RNA-seq). DNA-seq data were analyzable from 127 samples derived from 89 participants, and RNA-seq data were analyzable from 86 samples derived from 70 participants. We compared the bacterial microbiome and resistome between the two study arms and over time. The median number of doxycycline doses taken since enrollment by participants with DNA-seq data was zero (interquartile range (IQR): 0–7 doses) for the SOC arm and 42 (IQR: 27–64 doses) for the DP arm. Tetracycline ARGs were detected in all day-0 DNA-seq samples and in 85% of day-0 RNA-seq samples. The proportional mass of tetracycline ARGs in the resistome increased between day-0 and month-6 in DP participants from 46% to 51% in the metagenome (&lt;i&gt;P&lt;/i&gt; = 2.3 × 10&lt;sup&gt;−2&lt;/sup&gt;) and from 4% to 15% in the metatranscriptome (&lt;i&gt;P&lt;/i&gt; = 4.5 × 10&lt;sup&gt;−6&lt;/sup&gt;), but no statistically significant increases in other ARG classes were observed. Exposure to a higher number of doxycycline doses correlated with proportional enrichment of tetracycline ARGs in the metagenome (Spearman’s &lt;i&gt;ρ&lt;/i&gt; = 0.23, &lt;i&gt;P&lt;/i&gt; = 9.0 × 10&lt;sup&gt;−3&lt;/sup&gt;) and metatranscriptome (Spearman’s &lt;i&gt;ρ&lt;/i&gt; = 0.55, &lt;i&gt;P&lt;/i&gt; = 3.7 × 10&lt;sup&gt;−8&lt;/sup&gt;). Bacterial microbiome alpha diversity, beta diversity and total bacterial mass did not differ between day-0 and month-6 samples from DP participants when assessed by either DNA-seq or RNA-seq. In an abundance-based correlation analysis, we observed an increase over time in the strength of the correlation between tetracycline ARGs and specific bacterial taxa, including some common human pathogens. In sum, doxy-PEP use over a 6-month period was associated with an increase in the proportion of tetracycline ARGs comprising the gut resistome and an increase in the expression of tetracycline ARGs. At 6 months of doxy-PEP use, no residual differences were observed in alpha and beta diversity or taxonomic composition of the gut microbiome. As doxy-PEP is implemented as a public health strategy, further studies and population-level surveillance of doxycycline-resistant pathogens are needed to unde","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing the risk of post-surgery ischemic stroke caused by new atrial fibrillation","authors":"","doi":"10.1038/s41591-024-03262-6","DOIUrl":"https://doi.org/10.1038/s41591-024-03262-6","url":null,"abstract":"In a study of more than 250,000 adults who underwent noncardiac surgery, we found that new-onset postoperative atrial fibrillation (POAF) occurs at a predictable rate and is associated with an increased risk of ischemic stroke. Postoperative oral anticoagulation eliminated the POAF-attributable risk of stroke during the first year after surgery.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic CD5-specific CAR-T therapy for relapsed/refractory T-ALL: a phase 1 trial","authors":"Jing Pan, Yue Tan, Lingling Shan, Samuel Seery, Biping Deng, Zhuojun Ling, Jinlong Xu, Jiajia Duan, Zelin Wang, Kai Wang, Xinjian Yu, Qinlong Zheng, Xiuwen Xu, Guang Hu, Taochao Tan, Ying Yuan, Zhenglong Tian, Fangrong Yan, Yajing Han, Jiecheng Zhang, Xiaoming Feng","doi":"10.1038/s41591-024-03282-2","DOIUrl":"https://doi.org/10.1038/s41591-024-03282-2","url":null,"abstract":"<p>Refractory or relapsed T cell acute lymphoblastic leukemia (r/r T-ALL) patients have poor prognoses, due to the lack of effective salvage therapies. Recently, CD7-targeting chimeric antigen receptor (CAR)-T therapies show efficacy in patients with r/r T-ALL, but relapse with CD7 loss is common. This study evaluates a <i>CD5</i>-gene-edited CAR-T cell therapy targeting CD5 in 19 r/r T-ALL patients, most of whom had previously failed CD7 CAR-T interventions. CAR-T products were derived from previous transplant donors (Cohort A) or newly matched donors (Cohort B). Primary endpoints were dose-limiting toxicity at 21 days and adverse events within 30 days. Secondary endpoints were responses, pharmacokinetics and severe adverse events after 30 days. A total of 16 received infusions, 10 at target dose of 1 × 10⁶ kg⁻¹. All encountered grade 3–4 cytopenias and one had a grade 3 infection within 30 days. All patients (100%) achieved complete remission or complete remission with incomplete blood count recovery by day 30. At a median follow-up of 14.3 months, four received transplantation; three were in remission and one died of infection. Of 12 untransplanted patients, 2 were in remission, 3 relapsed, 5 died of infection and 2 of thrombotic microangiopathy. CAR-T cells persisted and cleared CD5⁺ T cells. CD5⁻ T cells, mostly <i>CD5</i>-gene-edited, increased but remained below normal levels. These results suggest this CD5-specific CAR-T intervention has a high remission rate for T-ALL patients. Evidence also suggests the risk of late-onset severe infection may be mitigated with consolidative transplantation. This study provides insights that could help to optimize this promising intervention. ClinicalTrials.gov registration: NCT05032599.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The inconvenient reality of AI-assisted embryo selection in IVF","authors":"Dorit C. Kieslinger, Cornelis B. Lambalk, Carlijn G. Vergouw","doi":"10.1038/s41591-024-03289-9","DOIUrl":"https://doi.org/10.1038/s41591-024-03289-9","url":null,"abstract":"Artificial intelligence is being hyped for its potential to revolutionize assisted reproduction, including embryo selection — but a new study reveals that the inflated expectations of new technologies are not always justified.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":null,"pages":null},"PeriodicalIF":82.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}