Med最新文献

{"title":"Gut microbiome model predicts response to neoadjuvant immunotherapy plus chemoradiotherapy in rectal cancer.","authors":"Zhengyang Yang, Jingxin Ma, Jiagang Han, Ang Li, Gang Liu, Yi Sun, Jianyong Zheng, Jie Zhang, Guangyong Chen, Rui Xu, Liting Sun, Cong Meng, Jiale Gao, Zhigang Bai, Wei Deng, Chenlin Zhang, Jianrong Su, Hongwei Yao, Zhongtao Zhang","doi":"10.1016/j.medj.2024.07.002","DOIUrl":"10.1016/j.medj.2024.07.002","url":null,"abstract":"<p><strong>Background: </strong>Accurate evaluation of the response to preoperative treatment enables the provision of a more appropriate personalized therapeutic schedule for locally advanced rectal cancer (LARC), which remains an enormous challenge, especially neoadjuvant immunotherapy plus chemoradiotherapy (nICRT).</p><p><strong>Methods: </strong>This prospective, multicenter cohort study enrolled patients with LARC from 6 centers who received nICRT. The dynamic variation in the gut microbiome during nICRT was evaluated. A species-level gut microbiome prediction (SPEED) model was developed and validated to predict the pathological complete response (pCR) to nICRT.</p><p><strong>Findings: </strong>A total of 50 patients were enrolled, 75 fecal samples were collected from 33 patients at different time points, and the pCR rate reached 42.4% (14/33). Lactobacillus and Eubacterium were observed to increase after nICRT. Additionally, significant differences in the gut microbiome were observed between responders and non-responders at baseline. Significantly higher abundances of Lachnospiraceae bacterium and Blautia wexlerae were found in responders, while Bacteroides, Prevotella, and Porphyromonas were found in non-responders. The SPEED model showcased a superior predictive performance with areas under the curve of 98.80% (95% confidence interval [CI]: 95.67%-100%) in the training cohort and 77.78% (95% CI: 65.42%-88.29%) in the validation cohort.</p><p><strong>Conclusions: </strong>Programmed death 1 (PD-1) blockade plus concurrent long-course CRT showed a favorable pCR rate and is well tolerated in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) patients with LARC. The SPEED model can be used to predict the pCR to nICRT based on the baseline gut microbiome with high robustness and accuracy, thereby assisting clinical physicians in providing individualized management for patients with LARC.</p><p><strong>Funding: </strong>This research was funded by the China National Natural Science Foundation (82202884).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761383","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":"Treatment of chronic hand eczema with topical anti-inflammatory drugs other than topical corticosteroids.","authors":"Hidehisa Saeki, Naoko Kanda","doi":"10.1016/j.medj.2024.08.009","DOIUrl":"https://doi.org/10.1016/j.medj.2024.08.009","url":null,"abstract":"<p><p>Chronic hand eczema is a fluctuating, inflammatory, pruritic disease of the hands and wrists that is commonly treated with topical corticosteroids and emollients. In a recent report in The Lancet, Bissonnette et al. demonstrated that delgocitinib cream showed superior efficacy versus a cream vehicle and was well tolerated over 16 weeks in adults with moderate to severe chronic hand eczema.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476409","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 tumor cornification and immune-infiltration-based scheme for anti-PD-1 plus chemotherapy response in advanced squamous cell lung carcinoma.","authors":"Minlin Jiang, Jiya Sun, Congli Hu, Lin Wu, Yun Fan, Zhehai Wang, Lianke Liu, Chunyan Wu, Fengying Wu, Guanghui Gao, Fei Li, Lei Wang, Xuefei Li, Lei Cheng, Bo Peng, Hui Zhou, Caicun Zhou","doi":"10.1016/j.medj.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.medj.2024.09.005","url":null,"abstract":"<p><strong>Background: </strong>Anti-PD-1 immunotherapy plus chemotherapy (combo) exhibits significantly prolonged survival for squamous cell lung cancer (LUSC). An exploration of predictive biomarkers is still needed.</p><p><strong>Methods: </strong>High-throughput RNA sequencing (RNA-seq) of 349 LUSC samples from the randomized, multi-center, phase 3 trial ORIENT-12 (ClinicalTrials.gov: NCT03629925) was conducted for biomarker discovery, followed by flow cytometry and multiplex immunohistochemistry (mIHC) in additional clinical cohorts, and in vitro experiments were performed for verification.</p><p><strong>Results: </strong>A high abundance of activated CD8⁺ T and CD56^bright natural killer (NK) cells benefited patients' outcomes (progression-free survival [PFS]; overall survival [OS]) with combo treatment. Tumor cornification level remarkably affected the infiltration of the two crucial immune cells. Thus, a novel scheme of LUSC immune infiltration and cornification characterization-based classification (LICC) was established for combo efficacy prediction. Patients who received combo treatment achieved significant PFS improvements in LICC1 (hazard ratio [HR] = 0.43, 95% confidence interval [CI]: 0.25-0.75, p = 0.0029) and LICC2 (HR = 0.32, 95% CI: 0.17-0.58, p = 0.0002) subtypes but not in the LICC3 subtype (HR = 0.86, 95% CI: 0.60-1.23, p = 0.4053). Via single-cell RNA-seq analysis, the tumor cornification signal was mainly mapped to SPRR3⁺ tumor cells, whose relationships with activated CD8⁺ T or CD56^bright NK cells were verified using flow cytometry and mIHC. Our data suggest that SPRR3⁺ tumor cells might evade immune surveillance via the CD24-SIGLEC10 (M2 macrophage) axis to maintain a suppressive tumor microenvironment.</p><p><strong>Conclusions: </strong>Tumor cornification greatly impacts immune infiltration, and the LICC scheme may guide clinical medication of anti-PD-1+chemo treatment in patients with LUSC.</p><p><strong>Funding: </strong>The study was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, Shanghia Multidisplinary Cooperation Building Project for Diagnosis and Treatment of Major Disease, and Innovent Biologics, Inc.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476404","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":"Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study.","authors":"Alan K Percy, Jeffrey L Neul, Timothy A Benke, Elizabeth M Berry-Kravis, Daniel G Glaze, Eric D Marsh, Amy M Barrett, Di An, Kathie M Bishop, James M Youakim","doi":"10.1016/j.medj.2024.06.007","DOIUrl":"10.1016/j.medj.2024.06.007","url":null,"abstract":"<p><strong>Background: </strong>Trofinetide was approved for the treatment of Rett syndrome (RTT) in patients aged ≥2 years based on the results of the 12-week, randomized, phase 3 LAVENDER study. In LILAC, a 40-week, open-label extension study of LAVENDER, trofinetide continued to improve the symptoms of RTT, with a similar safety profile as LAVENDER. Here, we report long-term safety and efficacy results of LILAC-2, a 32-month, open-label extension study.</p><p><strong>Methods: </strong>Females aged 5-22 years who completed LILAC were eligible to enter LILAC-2. Safety and tolerability were assessed with the incidence of adverse events (AEs). Efficacy was assessed with Rett Syndrome Behaviour Questionnaire (RSBQ) and Clinical Global Impression-Improvement (CGI-I) scores. Caregiver interviews explored the patient's experience with RTT and the efficacy of trofinetide during study participation.</p><p><strong>Findings: </strong>In total, 77 participants were enrolled in LILAC-2. The most common AEs were diarrhea (53.2%), COVID-19 (27.3%), and vomiting (19.5%). The mean (standard error [SE]) change in RSBQ score from LAVENDER baseline to week 104 of LILAC-2 was -11.8 (2.45). The mean (SE) CGI-I score from LILAC baseline to week 12 of LILAC-2 was 3.1 (0.10). Most caregivers (96%; n = 24/25) were satisfied or very satisfied with the benefits of trofinetide.</p><p><strong>Conclusions: </strong>Long-term treatment with trofinetide continued to improve RTT symptoms, without new safety concerns. Caregivers reported satisfaction with trofinetide related to improvements that were meaningful for their child and themselves.</p><p><strong>Funding: </strong>The study was supported by Acadia Pharmaceuticals (San Diego, CA, USA). This study was registered at ClinicalTrials.gov: NCT04776746.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724606","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":"Trofinetide treatment for Rett syndrome: Lessons to learn.","authors":"Daniela Tropea","doi":"10.1016/j.medj.2024.07.028","DOIUrl":"https://doi.org/10.1016/j.medj.2024.07.028","url":null,"abstract":"<p><p>The US FDA approval of trofinetide as the first pharmacological treatment to improve Rett syndrome's symptomatology marks a significant milestone with broad implications for various disorders. The LILAC trials demonstrate long-term safety and efficacy of trofinetide.¹^,² While further research is needed to fully resolve the condition, insights from trofinetide trials can inform strategies for future treatments and trials.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476410","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":"Efficacy, immunogenicity, and safety of a monovalent mRNA vaccine, ABO1020, in adults: A randomized, double-blind, placebo-controlled, phase 3 trial.","authors":"Suad Hannawi, Xiao-Hong Wu, Ralph Elvi Villalobos, Erlina Burhan, Ma Dovie Lallaine Borra, Rakesh Kumar Gupta, Grace P Aquitania, Blake Warren C Ang, Gelza Mae A Zabat, Camilo C Roa, Loreta Zoleta-De Jesus, Dan-Dan Yu, Meng Wang, Yan Wu, Wen-Jie Song, Bo Ying, Cheng-Feng Qin","doi":"10.1016/j.medj.2024.06.013","DOIUrl":"10.1016/j.medj.2024.06.013","url":null,"abstract":"<p><strong>Background: </strong>ABO1020 is a monovalent COVID-19 mRNA vaccine. Results from a phase 1 trial showed ABO1020 was safe and well tolerated, and phase 3 trials to evaluate the efficacy, immunogenicity, and safety of ABO1020 in healthy adults are urgently needed.</p><p><strong>Methods: </strong>We conducted a multinational, randomized, placebo-controlled, double-blind, phase 3 trial among healthy adults (ClinicalTrials.gov: NCT05636319). Participants were randomly assigned (1:1) to receive either 2 doses of ABO1020 (15 μg per dose) or placebo, administered 28 days apart. The primary endpoint was the vaccine efficacy in preventing symptomatic COVID-19 cases that occurred at least 14 days post-full vaccination. The second endpoint included the neutralizing antibody titers against Omicron BA.5 and XBB and safety assessments.</p><p><strong>Findings: </strong>A total of 14,138 participants were randomly assigned to receive either vaccine or placebo (7,069 participants in each group). A total of 366 symptomatic COVID-19 cases were confirmed 14 days after the second dose among 93 participants in the ABO1020 group and 273 participants in the placebo group, yielding a vaccine efficacy of 66.18% (95% confidence interval: 57.21-73.27, p < 0.0001). A single dose or two doses of ABO1020 elicited potent neutralizing antibodies against both BA.5 and XBB.1.5. The safety profile of ABO1020 was characterized by transient, mild-to-moderate fever, pain at the injection site, and headache.</p><p><strong>Conclusion: </strong>ABO1020 was well tolerated and conferred 66.18% protection against symptomatic COVID-19 in adults.</p><p><strong>Funding: </strong>National Key Research and Development Project of China, Innovation Fund for Medical Sciences from the CAMS, National Natural Science Foundation of China.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724552","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":"Expanding the frontiers of therapeutic options in hidradenitis suppurativa: The valid contribution of bimekizumab.","authors":"Elisa Molinelli, Edoardo De Simoni, Oriana Simonetti","doi":"10.1016/j.medj.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.medj.2024.08.005","url":null,"abstract":"<p><p>Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disorder with a significant negative impact on quality of life. Th17 axis has a central role in the pathogenesis of HS. Kimball et al. demonstrated the efficacy and safety of bimekizumab in two double-blind, placebo-controlled phase 3 studies (BE HEARD I-II), adding a new targeting option to the therapeutic armamentarium of HS.¹.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476408","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":"Preclinical assessment for translation to humans: The PATH approach for assessing supporting evidence for early-phase trials and innovative care.","authors":"Jonathan Kimmelman, Patrick Bodilly Kane, Selin Bicer, Benjamin Gregory Carlisle","doi":"10.1016/j.medj.2024.07.014","DOIUrl":"10.1016/j.medj.2024.07.014","url":null,"abstract":"<p><p>Early-phase trials and innovative care draw support from basic science, preclinical studies, and clinical research. Such evidential diversity presents a challenge for traditional ways of synthesizing evidence. In what follows, we review the limitations of existing approaches for communicating supporting evidence for early-phase trials. We then offer a structured approach, PATH (preclinical assessment for translation to humans). PATH is grounded in the premise that the case for administering novel strategies to patients requires connecting the dots between nine mechanistic steps supporting a clinical claim. Using PATH entails first parsing supporting evidence, assessing the strength of evidence at each step, and then assessing the strength of a chain of evidence linking drug administration to clinical effect. While PATH requires further refinement, the approach reduces some of the opacity, arbitrariness, and biases in current ways of presenting and assessing scientific support for early-phase trials and innovative care.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907820","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":"A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer.","authors":"Ning Li, Meng Qiu, Yanqiao Zhang, Mudan Yang, Linzhi Lu, Wei Li, Yuntao Ma, Xiaoming Hou, Guoping Sun, Mingquan Cai, Jingran Wang, Jianwei Lu, Diansheng Zhong, Zhibin Huo, Jingdong Zhang, Xianli Yin, Jun Deng, Zimin Liu, Hongming Pan, Ye Chen, Futang Yang, Haoyu Yu, Jing Li, Qingyu Wang, Jun Zhu, Jin Li","doi":"10.1016/j.medj.2024.06.004","DOIUrl":"10.1016/j.medj.2024.06.004","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor.</p><p><strong>Methods: </strong>This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25 mg/kg HLX22 (a novel anti-HER2 antibody) + HLX02 (trastuzumab biosimilar) + oxaliplatin and capecitabine (XELOX) (group A), 15 mg/kg HLX22 + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC).</p><p><strong>Findings: </strong>Between November 29, 2021, and June 6, 2022, 82 patients were screened; 53 were randomized to group A (n = 18), B (n = 17), and C (n = 18). With 14.3 months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. C, 15.1 vs. 8.2 months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. C, not reached vs. 8.2 months, HR 0.1 [95% CI 0.04-0.52]). Confirmed ORR was comparable among groups (A vs. B vs. C, 77.8% vs. 82.4% vs. 88.9%). Treatment-related adverse events (TRAEs) were observed in 18 (100%), 16 (94.1%), and 17 (94.4%) patients, respectively. One (5.6%) patient in group C reported a grade 5 TRAE.</p><p><strong>Conclusions: </strong>Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety.</p><p><strong>Funding: </strong>Shanghai Henlius Biotech, Inc.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580968","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":"Twice-yearly lenacapavir: A milestone for HIV prevention in young African women.","authors":"Silvia Nozza, Antonella Castagna","doi":"10.1016/j.medj.2024.08.008","DOIUrl":"https://doi.org/10.1016/j.medj.2024.08.008","url":null,"abstract":"<p><p>The PURPOSE 1 trial¹ demonstrated that after 52 weeks, no cisgender women acquired HIV infection after receiving subcutaneous twice-yearly lenacapavir. HIV incidence with lenacapavir was significantly lower than HIV incidence with daily oral emtricitabine/tenofovir alafenamide (F/TAF) or daily oral emtricitabine/tenofovir disoproxil fumarate (F/TDF). It is the first pre-exposure prophylaxis regimen with 100% efficacy in young women.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476411","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}