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{"title":"eNRGy: Making progress toward a future for NRG1 fusion-positive cancer.","authors":"Lucia Anna Muscarella, Massimo Di Maio","doi":"10.1016/j.medj.2025.100641","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100641","url":null,"abstract":"<p><p>The eNRGy trial demonstrated zenocutuzumab's efficacy in advanced cancer with NRG1 fusion, mainly non-small cell lung and pancreatic cancers.¹ Responses were observed across multiple tumor types identified through RNA-based next-generation sequencing, with low-grade adverse events. This suggests a potentially agnostic role of NRG1 fusions in solid tumors and underscores the need for comprehensive gene fusion testing in patients with cancer.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100641"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056682","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":"Bridging the gaps: Overcoming challenges of implementing AI in healthcare.","authors":"Xiaoyun Huang, Lei Gu, Jian Sun, Roland Eils","doi":"10.1016/j.medj.2025.100666","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100666","url":null,"abstract":"<p><p>Artificial intelligence (AI) in healthcare promises transformative advancements, from enhancing diagnostics to optimizing personalized treatments. Realizing its full potential, however, requires addressing key challenges, including explainability, bias & fairness, infrastructure, privacy, security, as well as ethical, regulatory and educational challenges. Bridging these gaps is essential to ensure AI's equitable and effective integration into clinical practice.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100666"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051152","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":"AMPLIFY: A second-generation BTK inhibitor for fixed-duration therapy in chronic lymphocytic leukemia.","authors":"Stefano Molica","doi":"10.1016/j.medj.2025.100665","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100665","url":null,"abstract":"<p><p>Recent advancements in chronic lymphocytic leukemia (CLL) treatment emphasize fixed-duration (FD) strategies, notably venetoclax with obinutuzumab or ibrutinib, now endorsed by ESMO guidelines. The AMPLIFY phase 3 trial highlights acalabrutinib-venetoclax combinations, demonstrating superior progression-free survival and manageable safety.¹ These findings support FD regimens as a paradigm shift, optimizing efficacy, safety, and patient convenience in frontline CLL therapy.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100665"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049853","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":"B cell depletion in lupus nephritis: From disappointments to hopes, despite some concerns.","authors":"Antoine Enfrein, Frédéric A Houssiau","doi":"10.1016/j.medj.2025.100640","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100640","url":null,"abstract":"<p><p>Lupus nephritis is the most common severe manifestation of systemic lupus erythematosus. B cells are key drivers of the disease as they produce autoantibodies that deposit in the kidneys, triggering inflammatory response and damage. The REGENCY trial¹ demonstrates that addition of the anti-CD20 monoclonal antibody obinutuzumab on top of standard-of-care significantly improves complete renal remission rate.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100640"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050693","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 and safety of anti-PD-1 versus anti-PD-L1 in perioperative immunotherapy: A comprehensive reanalysis of randomized controlled trials.","authors":"Chaoqi Zhang, Peng Wu, Dongyu Li, Junhan Zhou, Chuqi Lin, Xuanyu Gu, Dexin Shang, Ruijie Ma, Jingjing Liu, Guochao Zhang, Pan Wang, Yun Che, Qingpeng Zeng, Jilin Peng, Bohui Zhao, Nan Sun, Jie He","doi":"10.1016/j.medj.2025.100669","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100669","url":null,"abstract":"<p><strong>Background: </strong>Perioperative anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) immune checkpoint inhibitors improve outcomes, but optimal selection between agents remains debated. We compared the efficacy and safety of anti-PD-1 versus anti-PD-L1 in neoadjuvant/adjuvant settings.</p><p><strong>Methods: </strong>PubMed, Embase, Cochrane CENTRAL, and major oncology conferences (up to May 20, 2024) were systematically searched for randomized trials comparing anti-PD-1/PD-L1 with standard perioperative therapy. Data extraction followed PRISMA guidelines, including trial characteristics, efficacy outcomes (pathological response and survival outcome), and safety profiles. Indirect comparisons between agents were conducted through network meta-analysis employing the mirror principle, utilizing both frequentist and Bayesian methodologies.</p><p><strong>Findings: </strong>Thirty-one trials (14,974 patients) were analyzed. Anti-PD-1 demonstrated superior pathological complete response (relative risk [RR]: 1.65, 95% confidence interval [CI]: 1.18-2.29, p = 0.003), major pathological response (RR: 1.43, 95% CI: 1.04-1.96, p = 0.026), and disease-free survival (hazard ratio [HR] = 0.82, 95% CI: 0.71-0.96, p = 0.0106) versus anti-PD-L1. Safety profiles were comparable overall, though anti-PD-1 correlated with higher grade 3-5 immune-related adverse events (irAEs). Frequentist and Bayesian analyses yielded consistent results.</p><p><strong>Conclusions: </strong>Perioperative anti-PD-1 therapy shows enhanced efficacy but increased severe irAEs compared to anti-PD-L1, supporting agent-specific considerations in clinical practice. Further tumor-specific evaluations and mature data are warranted.</p><p><strong>Funding: </strong>This work is supported in part by the CAMS Innovation Fund for Medical Sciences (2024-I2M-ZD-004) and so on.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100669"},"PeriodicalIF":12.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051005","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":"Guselkumab in moderately to severely active ulcerative colitis: Another interleukin-23p19 subunit inhibitor or more?","authors":"Ambrogio Orlando, Fabio Salvatore Macaluso","doi":"10.1016/j.medj.2025.100605","DOIUrl":"10.1016/j.medj.2025.100605","url":null,"abstract":"<p><p>The QUASAR clinical development program evaluated the efficacy of guselkumab-an IL-23p19 subunit inhibitor-for the treatment of moderate-to-severe ulcerative colitis.¹ Guselkumab demonstrated rapid control of symptoms, as well as significant rates of objective disease remission. However, real-world evidence will be crucial to confirm these findings in patient subgroups that were not included in the QUASAR program.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 3","pages":"100605"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634784","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":"Integrating immunotherapy in the treatment of resectable gastric cancer: Are we on the right track?","authors":"Roberto Pazo-Cid, Paula Gomila Pons","doi":"10.1016/j.medj.2024.10.020","DOIUrl":"10.1016/j.medj.2024.10.020","url":null,"abstract":"<p><p>Long et al.¹ evaluated neoadjuvant (NAT) cadonilimab plus FLOT chemotherapy (ChT) in locally advanced gastric (G) and gastroesophageal junction (GEJ) adenocarcinoma, showing a pathological complete response (pCR) rate of 21.1% and an R0 resection rate of 100%. These findings align with other perioperative immunotherapy trials, although challenges remain in optimizing event-free survival (EFS).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 3","pages":"100543"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634828","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":"Arab founder variants: Contributions to clinical genomics and precision medicine.","authors":"Lama AlAbdi, Sateesh Maddirevula, Bayan Aljamal, Halima Hamid, Aisha Almulhim, Mais O Hashem, Yusra Algoos, Mashael Alqahtani, Shahad Albaloshi, Mohammed Alghamdi, Mohammed Alduaylij, Hanan E Shamseldin, Seba Nadeef, Nisha Patel, Firdous Abdulwahab, Omar Abouyousef, Tarfa Alshidi, Amal Jaafar, Mohamed Abouelhoda, Adel Alhazzani, Ahmed Alfares, Ahmad Qudair, Ahood Alsulaiman, Amal Alhashem, Arif O Khan, Aziza Chedrawi, Basel Alebdi, Fahad AlAjlan, Fawaz Alotaibi, Hamad Alzaidan, Hanaa Banjar, Hanem Abdelraouf, Hisham Alkuraya, Iman Abumansour, Khowlah Alfayez, Maha Tulbah, Mohammed Alowain, Mohammed Alqahtani, Mohammed El-Kalioby, Mohammad Shboul, Raashda Sulaiman, Saed Al Tala, Sameena Khan, Serdar Coskun, Sobaihi Mrouge, Walaa Alenazi, Zuhair Rahbeeni, Fowzan S Alkuraya","doi":"10.1016/j.medj.2024.10.005","DOIUrl":"10.1016/j.medj.2024.10.005","url":null,"abstract":"<p><strong>Background: </strong>Founder variants are ancestral variants shared by individuals who are not closely related. The large effect size of some of these variants in the context of Mendelian disorders offers numerous precision medicine opportunities.</p><p><strong>Methods: </strong>Using one of the largest datasets on Mendelian disorders in the Middle East, we identified 2,908 medically relevant founder variants derived from 18,360 exomes and genomes and investigated their contribution to the clinical annotation of the human genome.</p><p><strong>Findings: </strong>Strikingly, ∼34% of Arab founder variants are absent in gnomAD. We found a strong contribution of Arab founder variants to the identification of novel gene-disease links (n = 224) and the support/dispute (n = 81 support, n = 101 dispute) of previously reported candidate gene-disease links. The powerful segregation evidence generated by Arab founder variants allowed many ClinVar and Human Gene Mutation Database variants to be reclassified. Overall, 39.5% of diagnostic reports from our clinical lab are based on founder variants, and 19.41% of tested individuals carry at least one pathogenic founder variant. The presumptive loss-of-function mechanism that typically underlies autosomal recessive diseases means that Arab founder variants also offer unique opportunities in \"druggable genome\" research. Arab founder variants were also informative of migration patterns in the Middle East consistent with documented historical accounts.</p><p><strong>Conclusions: </strong>We highlight the contribution of founder variants from an under-represented population group to precision medicine and inform future prevention programs. Our study also sheds light on the added value of these variants in supplementing other lines of research in tracing population history.</p><p><strong>Funding: </strong>There is no funding for this work.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100528"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589951","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":"Neoadjuvant cadonilimab plus FLOT chemotherapy in locally advanced gastric/gastroesophageal junction adenocarcinoma: A multicenter, phase 2 study.","authors":"Bo Long, Huinian Zhou, Zeyuan Yu, Junmin Zhu, Hanteng Yang, Zeping Huang, Dengwen Wei, Shigong Chen, Xiaojun Yang, Xiaoning Zhao, Wenjuan Zhang, Hong Yan, Xiaoying Guan, Long Li, Gengyuan Zhang, Hongwei Yu, Shengfu Che, Zhongti Gao, Xiangyan Jiang, Changjiang Luo, Jie Mao, Da Zhao, Yumin Li, Zebin Jiang, Zuoyi Jiao","doi":"10.1016/j.medj.2024.10.008","DOIUrl":"10.1016/j.medj.2024.10.008","url":null,"abstract":"<p><strong>Background: </strong>Treatment with cadonilimab and chemotherapy has shown promise as a first-line treatment for gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, its application in neoadjuvant settings has not yet been documented.</p><p><strong>Methods: </strong>This multicenter, phase 2 trial (ChiCTR2200066893) was conducted at four hospitals across China. Treatment-naive patients with locally advanced G/GEJ adenocarcinoma (cT3/4, N+, M0) and who were human epidermal growth factor receptor 2 negative received 3-cycle or 4-cycle neoadjuvant treatment of cadonilimab plus FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy, followed by gastrectomy and 4-cycle adjuvant FLOT chemotherapy. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included major pathological response (MPR), overall response rate (ORR), disease control rate (DCR), R0 resection rate, downstaging rate, and safety.</p><p><strong>Findings: </strong>Between December 23, 2022, and December 15, 2023, 32 of 38 patients completed the scheduled treatment, achieving an R0 resection rate of 100% (32/32). The pCR rate was 21.1% (8/38, 90% confidence interval [CI]: 9.7-32.4), and the MPR rate was 44.7% (17/38, 90% CI: 30.9-58.5). Radiological evaluations were available for 28 of 38 patients by blinded independent central review. The ORR was 60.7% (17/28, 90% CI: 44.7-76.7), and the DCR was 100.0% (28/28, 90% CI: 100.0-100.0). Tumor downstaging occurred in 71.9% of patients (23/32), with consistent efficacy across all populations observed in the subgroup analysis. Grade 3 adverse events occurred in 31.6% of patients without severe safety issues.</p><p><strong>Conclusions: </strong>Neoadjuvant cadonilimab plus FLOT chemotherapy treatment exhibits promising efficacy with manageable toxicities in locally advanced G/GEJ adenocarcinoma, providing preliminary evidence for further investigation.</p><p><strong>Funding: </strong>This study was funded by Akeso Biopharma.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100531"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629129","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 new standard for HCC: The high stakes of TACE-immunotherapy combinations.","authors":"Antonio D'Alessio, Lorenza Rimassa","doi":"10.1016/j.medj.2025.100635","DOIUrl":"10.1016/j.medj.2025.100635","url":null,"abstract":"<p><p>Transarterial chemoembolization (TACE) has long been the standard for intermediate-stage hepatocellular carcinoma (HCC), but two recent phase 3 trials have redefined treatment paradigms. The EMERALD-1¹ and LEAP-012² trials demonstrated significant progression-free survival improvement with TACE combined with durvalumab/bevacizumab or pembrolizumab/lenvatinib, respectively, but doubts remain regarding the patient selection and the toxicity of these novel combinations.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 3","pages":"100635"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634801","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}