Annual review of medicinePub Date : 2026-01-01Epub Date: 2025-10-29DOI: 10.1146/annurev-med-050224-103456
Magali Noval Rivas, Moshe Arditi
{"title":"Kawasaki Disease Vasculitis: From Diagnosis to New Concepts in Pathophysiology and Therapeutic Approaches.","authors":"Magali Noval Rivas, Moshe Arditi","doi":"10.1146/annurev-med-050224-103456","DOIUrl":"10.1146/annurev-med-050224-103456","url":null,"abstract":"<p><p>Kawasaki disease (KD) is an acute, self-limiting vasculitis that primarily affects children under 5 years old. KD manifests as a persistent fever in the presence of mucocutaneous inflammation and lymphadenopathy, which in severe cases leads to the development of coronary artery aneurysms (CAAs). While early intervention with high-dose intravenous immunoglobulin and aspirin significantly lowers the risk of CAAs, up to 20% of patients with KD are resistant to intravenous immunoglobulin and face a substantially higher risk of developing coronary complications, highlighting the urgent need for more effective adjunctive and rescue therapies. Moreover, coronary abnormalities may persist after the apparent resolution of aneurysms, and cardiac complications extend into adolescence and adulthood. Murine models mimicking KD vasculitis have played a pivotal role in advancing our understanding of the disease's immunopathology, shedding light on the immune mechanisms driving its cardiovascular complications. Here, we summarize the current understanding of KD immunopathogenesis and its cardiovascular complications, as well as recent preclinical findings that are facilitating the development of novel therapeutic strategies, offering hope for improved management of KD in the future.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":" ","pages":"87-102"},"PeriodicalIF":22.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399448","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}
Zhimin Fu, Yuxin Yang, Mina K Chung, Feixiong Cheng
{"title":"Artificial Intelligence to Guide Repurposing of Drugs.","authors":"Zhimin Fu, Yuxin Yang, Mina K Chung, Feixiong Cheng","doi":"10.1146/annurev-med-050224-122802","DOIUrl":"10.1146/annurev-med-050224-122802","url":null,"abstract":"<p><p>With the pharmacokinetics, dosing, safety, and manufacturing of approved or investigational drugs already well-characterized, drug repurposing and repositioning offer emerging strategies to rapidly develop effective treatments for various challenging diseases. However, the growing mass of genetic and multiomics data has not been effectively explored by the drug repurposing community due to a lack of accurate approaches. This review aims to be an authoritative, critical, and accessible review and discussion of general interest to the drug repurposing community concerning the use of artificial intelligence (AI) and machine learning (ML) tools. Emerging questions include what is achievable with AI in this domain and what its impact will be, what AI and ML embrace, and how we, as geneticists, pharmacologists, and computational scientists, can contribute to the discovery of new, inexpensive, and affordable repurposable medicines. The fast growth of genetics and multiomics data (genomics, transcriptomics, proteomics, metabolomics, and radiomics) and electronic health records in diverse populations contributes to answering questions, including how to rapidly identify effective repurposable medicines, what a clinically meaningful effect size in trials is, and what the potential implications for precision medicine are. This review discusses AI and ML for drug repurposing in the context of genetics, multiomics, real-world data collection, and crowdsourcing of knowledge. We conclude by considering questions on how AI and ML methodologies can unite the diverse aspects of translational medicine for emerging treatment development in human-challenging diseases.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":"77 1","pages":"381-398"},"PeriodicalIF":22.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12854511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058996","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}
Annual review of medicinePub Date : 2026-01-01Epub Date: 2025-11-18DOI: 10.1146/annurev-med-050124-040555
Anne Sophie Sølling, Bente L Langdahl, Felicia Cosman
{"title":"Recent Advances in Osteoporosis Therapeutics.","authors":"Anne Sophie Sølling, Bente L Langdahl, Felicia Cosman","doi":"10.1146/annurev-med-050124-040555","DOIUrl":"10.1146/annurev-med-050124-040555","url":null,"abstract":"<p><p>Postmenopausal osteoporosis is a chronic progressive disease related to estrogen deficiency at menopause, aging, and superimposed genetic and environmental factors. Many patients with osteoporosis are not diagnosed, and the majority are not treated. Current therapies for osteoporosis include antiresorptive treatments, including bisphosphonates, denosumab, and raloxifene, and osteoanabolic treatments, including teriparatide, abaloparatide, and romosozumab, which is a dual-action agent. Sequential therapies aim to optimize fracture prevention and bone density outcomes for long-term management. Recent guidelines have suggested categorical risk stratification and a goal-directed individualized therapy strategy. New treatments under investigation also hold promise for further improving bone health in postmenopausal osteoporosis.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":" ","pages":"433-448"},"PeriodicalIF":22.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145547932","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":"CAR T Cell Toxicities and Emerging Treatment Strategies.","authors":"Amanda M Lulu, Erica Steele, Daniel W Lee","doi":"10.1146/annurev-med-050224-120336","DOIUrl":"https://doi.org/10.1146/annurev-med-050224-120336","url":null,"abstract":"<p><p>Having already revolutionized outcomes for relapsed or refractory B cell malignancies and multiple myeloma, chimeric antigen receptor (CAR) T cell therapy is on the cusp of significantly impacting those with solid tumors. However, antitumor response is frequently associated with acute toxicities due to immune hyperactivation, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, immune effector cell-associated hematotoxicity, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. We discuss the clinical presentations, evaluation, management, risk factors, and pathophysiologies of these toxicities and briefly describe emerging toxicity mitigation strategies.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":"77 1","pages":"219-237"},"PeriodicalIF":22.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058965","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":"Immunoglobulin A Nephropathy: New Treatment Options.","authors":"Arun Rajasekaran, Dana V Rizk, Kirk N Campbell","doi":"10.1146/annurev-med-043024-015024","DOIUrl":"https://doi.org/10.1146/annurev-med-043024-015024","url":null,"abstract":"<p><p>Immunoglobulin A nephropathy (IgAN) remains the leading primary glomerular disease worldwide, with a majority of patients reaching kidney failure within their lifetimes. IgAN is a heterogeneous glomerular disorder characterized by mesangial deposition of galactose-deficient immunoglobulin A1 containing immune complexes that induce glomerular injury and nephron loss. The primary therapeutic goal in treating IgAN is reduction of nephron loss from the time of diagnosis. Management ideally incorporates interventions targeting both immunologic and nonspecific chronic kidney disease pathomechanisms. Multitargeted approaches that simultaneously target the production of pathogenic immunoglobulin A immune complexes, address the consequences of ongoing nephron loss, halt glomerular inflammation, and inhibit profibrotic signals in the glomerulus and tubulointerstitium will provide maximal benefit. Given significant advances in the understanding of disease pathogenesis and the acceptance of surrogate outcomes (including proteinuria reduction) for accelerated drug approval, there has been a plethora of pharmacological agents recently evaluated and approved to treat IgAN. This review highlights the latest therapeutic developments in the field.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":"77 1","pages":"267-279"},"PeriodicalIF":22.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058988","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":"Accessibility of Somatic Genetic Testing for Cancer Treatment Decisions.","authors":"Madison Klavans, Fernanda B Musa, Marilyn Huang","doi":"10.1146/annurev-med-050124-082437","DOIUrl":"https://doi.org/10.1146/annurev-med-050124-082437","url":null,"abstract":"<p><p>Advances in cancer genomics have significantly influenced and improved oncologic treatments in recent years. Somatic genetic testing, which assesses for gene amplification and acquired mutations in tumor tissue, enables the identification of actionable mutations (i.e., biomarkers) to determine patients who may benefit from targeted therapies. Despite the progress made in somatic genetic testing, broad accessibility and adoption have been limited due to multifactorial barriers. Systematically addressing obstacles to somatic genetic testing is required to enhance availability, facilitate cancer treatments, and ultimately improve patient care.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":"77 1","pages":"207-218"},"PeriodicalIF":22.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058998","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}
Monica A Tincopa, Elizabeth K Speliotes, Luca Valenti, Rohit Loomba
{"title":"Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis-Related Fibrosis: Therapeutic Options and Approaches to Treatment.","authors":"Monica A Tincopa, Elizabeth K Speliotes, Luca Valenti, Rohit Loomba","doi":"10.1146/annurev-med-050324-124753","DOIUrl":"https://doi.org/10.1146/annurev-med-050324-124753","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disease impacting one-third of the adult population worldwide. MASLD has substantial associated morbidity and mortality, including progression to cirrhosis with the need for liver transplantation and development of hepatocellular carcinoma. Individuals with metabolic dysfunction-associated steatohepatitis (MASH), the more aggressive subtype of MASLD that includes hepatocyte injury, and stage 2 fibrosis or above are at the highest risk for adverse liver-related outcomes and overall mortality. Identification of high-risk individuals is key as these patients would benefit from directed pharmacotherapy for MASH. Additional directed pharmacotherapy agents are in development for MASH and hepatic fibrosis across various mechanisms of action. This review focuses on therapeutic options for and approaches to treatment in MASLD, including emerging agents.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":"77 1","pages":"103-115"},"PeriodicalIF":22.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058940","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":"Microscopic Colitis: Evidence-Based Guide to Diagnosis and Management.","authors":"Sara Ghoneim, Michael G Drage, Kristin E Burke","doi":"10.1146/annurev-med-050124-092157","DOIUrl":"https://doi.org/10.1146/annurev-med-050124-092157","url":null,"abstract":"<p><p>Microscopic colitis (MC), which predominately affects older adults, is a chronic inflammatory bowel disease characterized by watery diarrhea. Diagnosis relies on histological examination, as there are no established biomarkers to facilitate noninvasive diagnosis, and endoscopic findings are typically unremarkable. MC is classified into subtypes of lymphocytic and collagenous colitis. First-line therapy is budesonide (9 mg/day for 6-8 weeks), which induces remission effectively. However, relapse rates are high, necessitating alternative treatment strategies. Long-term maintenance strategies include low-dose budesonide, bile salt binders, antidiarrheals, and advanced therapies for refractory cases.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":"77 1","pages":"253-266"},"PeriodicalIF":22.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058949","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":"A New Era in the Medical Management of Obesity.","authors":"Florence Porterfield, Anam Fatima, Brunna Boaventura, Ayush Madhar, Gitanjali Srivastava, Fatima Cody Stanford","doi":"10.1146/annurev-med-043024-125437","DOIUrl":"https://doi.org/10.1146/annurev-med-043024-125437","url":null,"abstract":"<p><p>A new era in obesity management is emerging, characterized by the development of more effective treatments and healthcare strategies. A paradigm shift in obesity care calls for a more integrated, community-based approach that bridges the gap between medical management and bariatric surgery. This review explores important pillars related to obesity management, encompassing aspects related to the pathophysiology of the disease; treatments related to behavioral, nutritional, pharmacotherapeutic, and surgical approaches; and stigma mitigation.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":"77 1","pages":"131-146"},"PeriodicalIF":22.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058951","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}
Annual review of medicinePub Date : 2026-01-01Epub Date: 2025-10-31DOI: 10.1146/annurev-med-043024-012626
Maria Effenberger, Herbert Tilg
{"title":"Potential Health Risks of Artificial Sweeteners.","authors":"Maria Effenberger, Herbert Tilg","doi":"10.1146/annurev-med-043024-012626","DOIUrl":"10.1146/annurev-med-043024-012626","url":null,"abstract":"<p><p>Artificial sweeteners are widely used worldwide, yet their potential health effects remain a topic of debate. Recent studies suggest that artificial sweeteners, both nutritive and nonnutritive, may stimulate appetite, leading to increased caloric intake, a higher body mass index, and a greater risk of obesity. These metabolic changes are associated with an elevated risk of type 2 diabetes and cardiovascular diseases. Moreover, emerging preclinical evidence indicates that artificial sweeteners may influence cancer biology, potentially affecting tumor progression. This review examines the impact of artificial sweeteners on metabolic health, cardiovascular risk, and carcinogenesis, emphasizing the need for further research to clarify their long-term safety and health implications.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":" ","pages":"117-130"},"PeriodicalIF":22.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421071","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}