Oveis Jamialahmadi、Shahir Mowlaei、Kyla Z Gelev、Rosellina M Mancina、Valentina Flagiello、Julia Kozlitina、Päivi Pajukanta、Luca Valenti、Stefano Romeo
作者机构
Centre for Reproduction, Metabolism and Molecular Medicine (CeRM), Department of Medicine, Karolinska Institute, Huddinge, Sweden. oveis.jamialahmadi@ki.se.
Centre for Reproduction, Metabolism and Molecular Medicine (CeRM), Department of Medicine, Karolinska Institute, Huddinge, Sweden.
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Department of Life Science, Health, and Health Professions, Link Campus University, Rome, Italy.
Operative Research Unit of Clinical Medicine and Hepatology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
The Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA.
Institute for Precision Health, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
Precision Medicine and Biological Resource Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
Centre for Reproduction, Metabolism and Molecular Medicine (CeRM), Department of Medicine, Karolinska Institute, Huddinge, Sweden. stefano.romeo@ki.se.
Department of Endocrinology, Karolinska University Hospital, Huddinge, Sweden. stefano.romeo@ki.se.
Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy. stefano.romeo@ki.se.
Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. stefano.romeo@ki.se.
Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. stefano.romeo@ki.se.
技术路线
MRI衍生肝脏甘油三酯含量数据（71,488名欧洲 ancestry UK Biobank参与者）→全基因组关联研究荟萃分析→识别60个独立位点（31个新位点）并估计SNP遗传力为25%→整合精细定位与基因优先级分析提名48个位点的候选效应基因→在临床诊断的代谢功能障碍相关脂肪性肝病荟萃分析（42,163例病例和1,646,254例对照）中验证31个新位点中的14个→多基因风险评分与肝硬化（OR 2.71）和肝细胞癌（OR 7.47）风险关联分析→与多基因风险评分相关的血浆蛋白通路富集分析（代谢重塑和炎症通路，肝脏富集蛋白特征增加、内脏脂肪特征减少）
Susan DeWolf、Steven J Siegel、Joseph Schmalz、Wael Saber、Alexandre Albanese、Jiayi Dong、Michael J Martens、Brent Logan、Lorenzo Iovino、Kayleigh Ingersoll-Ohmdahl、Nicholas Winn、Edward Chen、James Kaminski、Donna Neuberg、Kyle Hebert、Paula Keskula、Jillian Zavistaski、Lea Steinberg、Isabella Schichter、Zoe Katsamakis、Lorenzo Cagnin、Vanessa Hernandez、Makya Warren、Kristy Applegate、Merav Bar、Saurabh Chhabra、Sung Won Choi、William Clark、Suman Das、Robert Jenq、Richard J Jones、John E Levine、Hemant Murthy、Armin Rashidi、Marcie Riches、Karamjeet Sandhu、Anthony D Sung、Karilyn Larkin、Monzr M Al Malki、Mahasweta Gooptu、Hany Elmariah、Amin Alousi、Lyndsey Runaas、Brian Shaffer、Andrew Rezvani、Najla El Jurdi、Alison W Loren、Danielle Scheffey、Catherine Sanders、Mehdi Hamadani、Jarrod A Dudakov、Stephanie Bien、Harlan Robins、Mary Horowitz、Javier Bolaños-Meade、Shernan Holtan、Ami S Bhatt、Miguel-Angel Perales、Leslie S Kean
作者机构
Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pediatrics, Harvard Medical School and Divisions of Infectious Diseases and Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
Adaptive Biotechnologies, Seattle, WA, USA.
Department of Medicine, Medical College of Wisconsin and Center for International Blood and Marrow Transplant Research (CIBMTR), Milwaukee, WI, USA.
Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
CIBMTR and Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA.
CIBMTR and Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Emmes, Rockville, MD, USA.
Division of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA.
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Division of Hematology-Oncology and Palliative Care, Virginia Commonwealth University, Richmond, VA, USA.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and the Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Division of Hematology-Oncology and Blood and Marrow Transplant and Cellular Therapy Programs, Mayo Clinic, Jacksonville, FL, USA.
CIBMTR, Milwaukee, WI, USA.
Division of Hematologic Malignancies and Cellular Therapy, Kansas University Medical Center, Kansas City, KS, USA.
Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Department of Hematology and Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer and Research Institute, Tampa, FL, USA.
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center and Department of Immunology, University of Washington, Seattle, WA, USA.
Blood and Marrow Transplantation Section, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Division of Hematology, Departments of Medicine and Genetics, Stanford University, Palo Alto, CA, USA.
Department of Pediatrics, Harvard Medical School, Division of Hematology/Oncology, Boston Children's Hospital, and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Remibrutinib是一种高选择性、强效、共价、可穿透中枢神经系统的口服BTK抑制剂。REMODEL-1和REMODEL-2为两项相同的随机、双盲、双模拟、活性对照、平行组、事件驱动Ⅲ期试验，在46个国家407个中心开展，纳入18-55岁、EDSS评分0-5.5、有近期疾病活动证据的复发型多发性硬化患者，按1:1随机接受口服remibrutinib 100 mg每日两次或特立氟胺14 mg每日一次，主要终点为年化复发率（ARR）。2021年12月13日至2025年12月30日筛查2632例，随机分配2007例；REMODEL-1纳入1000例，REMODEL-2纳入1007例。remibrutinib组ARR显著低于特立氟胺组：REMODEL-1为0.073 vs 0.112（RR 0.648，95%CI 0.453-0.927；p=0.018），REMODEL-2为0.080 vs 0.116（RR 0.688，95%CI 0.487-0.972；p=0.034）。最常见不良事件为上呼吸道感染、鼻咽炎、腹泻和脱发；导致停药的不良事件remibrutinib组较少（3.1% vs 5.8%），安全性与其他适应症一致，无肝脏安全性担忧。研究表明remibrutinib优于特立氟胺且安全性良好，支持其作为复发型多发性硬化潜在新型口服治疗选择。
Department of Neurology and Neurophysiology, University of Freiburg, Freiburg, Germany; Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia. Electronic address: heinz.wiendl@uniklinik-freiburg.de.
Department of Neurology, Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH, USA.
Turku PET Centre, Clinical Neurosciences and InFLAMES Research Flagship, University of Turku, Turku, Finland; Neurocenter, Turku University Hospital, Turku, Finland.
Brigham Multiple Sclerosis Center and Division of Neuroimmunology, Mass General Brigham, Boston, MA, USA.
Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
Joi Life Wellness Neurology Clinic, Smyrna, GA, USA.
Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland.
MedPolonia, Outpatient MS Clinic, Poznań, Poland; Department of Medical Education and Communication, Poznan University of Medical Sciences, Poznań, Poland.
Novartis Pharma, Basel, Switzerland.
Novartis Ireland, Dublin, Ireland.
Novartis Institutes for Biomedical Research, Shanghai, China.
Novartis Pharmaceuticals Corporation, Cambridge, MA, USA.
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Barcelona, Spain.
为什么值得关注
AI 辅助短评，基于标题和摘要整理该研究构建交互式基准，评估语言模型在序贯诊断中的表现，AI系统在NEJM CPC病例和MIMIC-IV-ED数据上诊断准确率显著高于全科医生。但结果限于受控基准环境，未涉及真实临床验证，且未报告检查成本的具体比较数据。其模拟医生小组和成本效益选择的思路值得关注，但向临床转化仍需前瞻性研究支持。