Aaron M. Williams, John Trahanas, Swaroop Bommareddi, Kevin C. McGann, Awab Ahmad, Brian Lima, Chen Chia Wang, Mark Petrovic, Stephen Devries, Joshua Lowman, Tarek Absi, Eric Quintana, Hasan Siddiqi, Kaushik Amancherla, Marshall Brinkley, Stacy Tsai, Jonathan N. Menachem, Dawn Pedrotty, Aniket S. Rali, Suzanne Sacks, Sandip Zalawadiya, Joey Lepore, Mias Pretorious, Kelly Schlendorf, Matthew Bacchetta, Ashish S. Shah
Importance Rapid recovery with extended ultraoxygenated preservation (REUP) has shown promise in adult donation after circulatory death (DCD) heart transplant when used in younger donor populations (aged 16-30 years) and/or for hearts with shorter ischemic times (<4 hours). Objective To assess the feasibility of the REUP technique in adult DCD heart transplant, without regard to donor age or anticipated ischemic time. Design, Setting, and Participants Case series of 24 patients to undergo REUP-recovered DCD adult heart transplant at a single high-volume heart transplant center in the United States from November 2024 to July 2025. Exposure REUP used for DCD cardiac allograft recovery without preimplant donor heart reanimation or machine perfusion. Main Outcomes and Measures Severe primary graft dysfunction, 30-day survival, and acute rejection on first endomyocardial biopsy. Results Twenty-four REUP-recovered DCD hearts were transplanted, with a mean donor age of 32 years and 9 donors (38%) older than 40 years. Fifty percent of recipients had prior sternotomy. The mean time from initial declaration of donor death to flush was 9 minutes. Fifteen donor hearts (60%) had a total ischemic time longer than 4 hours, including 1 that was 8 hours. Among recipients, 30-day survival was 96%. Only 1 patient (4%) had severe primary graft dysfunction, and 1 other patient (4%) had secondary graft dysfunction. On initial endomyocardial biopsy, 1 patient (4%) had acute cellular rejection grade 2R; no cases of antibody-mediated rejection were observed. Conclusions and Relevance This study demonstrates the safety, feasibility, and efficacy of REUP for DCD heart recovery without donor heart reanimation in a broad population of donors and recipients and without regard to anticipated ischemic time. Given the high cost and complexity of current DCD heart recovery strategies, as well as ethical concerns surrounding normothermic regional perfusion, REUP may prove to be a promising procurement method. Further study is required to support continued expansion of this novel technique.
{"title":"Donation After Circulatory Death Heart Transplant Without Preimplant Reanimation Using Rapid Ultraoxygenated Recovery","authors":"Aaron M. Williams, John Trahanas, Swaroop Bommareddi, Kevin C. McGann, Awab Ahmad, Brian Lima, Chen Chia Wang, Mark Petrovic, Stephen Devries, Joshua Lowman, Tarek Absi, Eric Quintana, Hasan Siddiqi, Kaushik Amancherla, Marshall Brinkley, Stacy Tsai, Jonathan N. Menachem, Dawn Pedrotty, Aniket S. Rali, Suzanne Sacks, Sandip Zalawadiya, Joey Lepore, Mias Pretorious, Kelly Schlendorf, Matthew Bacchetta, Ashish S. Shah","doi":"10.1001/jama.2025.25169","DOIUrl":"https://doi.org/10.1001/jama.2025.25169","url":null,"abstract":"Importance Rapid recovery with extended ultraoxygenated preservation (REUP) has shown promise in adult donation after circulatory death (DCD) heart transplant when used in younger donor populations (aged 16-30 years) and/or for hearts with shorter ischemic times (<4 hours). Objective To assess the feasibility of the REUP technique in adult DCD heart transplant, without regard to donor age or anticipated ischemic time. Design, Setting, and Participants Case series of 24 patients to undergo REUP-recovered DCD adult heart transplant at a single high-volume heart transplant center in the United States from November 2024 to July 2025. Exposure REUP used for DCD cardiac allograft recovery without preimplant donor heart reanimation or machine perfusion. Main Outcomes and Measures Severe primary graft dysfunction, 30-day survival, and acute rejection on first endomyocardial biopsy. Results Twenty-four REUP-recovered DCD hearts were transplanted, with a mean donor age of 32 years and 9 donors (38%) older than 40 years. Fifty percent of recipients had prior sternotomy. The mean time from initial declaration of donor death to flush was 9 minutes. Fifteen donor hearts (60%) had a total ischemic time longer than 4 hours, including 1 that was 8 hours. Among recipients, 30-day survival was 96%. Only 1 patient (4%) had severe primary graft dysfunction, and 1 other patient (4%) had secondary graft dysfunction. On initial endomyocardial biopsy, 1 patient (4%) had acute cellular rejection grade 2R; no cases of antibody-mediated rejection were observed. Conclusions and Relevance This study demonstrates the safety, feasibility, and efficacy of REUP for DCD heart recovery without donor heart reanimation in a broad population of donors and recipients and without regard to anticipated ischemic time. Given the high cost and complexity of current DCD heart recovery strategies, as well as ethical concerns surrounding normothermic regional perfusion, REUP may prove to be a promising procurement method. Further study is required to support continued expansion of this novel technique.","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048289","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}
Sinead Stoneman, Jia Wei Teh, Michelle Marie O’Shaughnessy
Importance IgA nephropathy (IgAN) is a chronic kidney disease involving deposition of IgA-containing immune complexes in the glomerulus, causing glomerular inflammation and scarring. It is the most common immune-mediated glomerular disease worldwide, and affects an estimated 198 887 to 208 184 persons in the US. Up to 50% of patients with IgAN develop kidney failure within 10 years of diagnosis. Observations IgAN typically presents with nephritic syndrome and usually occurs in younger adults, with a mean age at diagnosis of 34 to 45 years. Incidence is highest in East Asia. Approximately 60% of cases are detected incidentally with hematuria or proteinuria on urinalysis. Up to 30% of patients present with episodic visible hematuria, often concomitantly with an upper respiratory or gastrointestinal tract infection (synpharyngitic hematuria). Less common presentations include nephrotic syndrome (<5%) and rapidly progressive glomerulonephritis (<5%). When IgAN is suspected (due to hematuria, proteinuria, or reduced kidney function), initial workup should include quantification of proteinuria and assessment for other causes of nephritic syndrome (eg, lupus nephritis). Adults with suspected IgAN and proteinuria greater than or equal to 0.5 g per day should undergo kidney biopsy. The diagnosis of primary IgAN is based on presence of IgA-dominant immune deposits in the glomerular mesangium after excluding other causes of this histologic appearance, ie, IgA vasculitis, IgA-dominant infection-related glomerulonephritis, and secondary IgAN from diseases such as cirrhosis, inflammatory bowel disease, celiac disease, infection (eg, viral hepatitis), and autoimmune diseases (eg, axial spondyloarthritis). Based on the Kidney Disease: Improving Global Outcomes 2025 clinical practice guideline for the management of IgAN, treatment for patients with proteinuria greater than 0.5 g per day includes behavioral modifications (eg, dietary sodium <2 g/d, smoking cessation, weight control, exercise), antihypertensive medications for goal blood pressure less than 120/70 mm Hg, and therapies to reduce the formation of IgA-containing immune complexes (eg, targeted-release budesonide), decrease glomerular injury (eg, systemic glucocorticoids, iptacopan), and manage existing IgAN-induced nephron loss (eg, renin-angiotensin system inhibitor or dual endothelin angiotensin receptor antagonist [eg, sparsentan] alone or in combination with a sodium-glucose cotransporter 2 inhibitor). Conclusions and Relevance IgAN is the leading cause of immune-mediated glomerular disease worldwide. Patients with suspected IgAN and proteinuria greater than or equal to 0.5 g per day should undergo kidney biopsy to confirm the diagnosis. Treatment of IgAN includes behavioral modifications, blood pressure management, and therapies to decrease formation of IgA-containing immune complexes (eg, targeted-release budesonide), reduce immune complex–mediated glomerular injur
IgA肾病（IgAN）是一种慢性肾脏疾病，涉及肾小球中含有IgA的免疫复合物沉积，引起肾小球炎症和瘢痕形成。它是世界上最常见的免疫介导的肾小球疾病，在美国估计有198887至208184人受到影响。高达50%的IgAN患者在确诊后10年内发生肾衰竭。IgAN通常表现为肾病综合征，通常发生在较年轻的成年人，诊断时的平均年龄为34至45岁。发病率在东亚最高。大约60%的病例在尿液分析中偶然发现血尿或蛋白尿。高达30%的患者表现为偶发性可见血尿，常伴有上呼吸道或胃肠道感染（咽喉性血尿）。不太常见的表现包括肾病综合征（<5%）和快速进展的肾小球肾炎（<5%）。当怀疑IgAN（由于血尿、蛋白尿或肾功能下降）时，最初的检查应包括蛋白尿的量化和肾病综合征（如狼疮性肾炎）的其他原因的评估。成人疑似IgAN和蛋白尿大于或等于每天0.5 g应进行肾活检。原发性IgAN的诊断是基于肾小球系膜中存在IgA显性免疫沉积，排除了这种组织学表现的其他原因，即IgA血管炎、IgA显性感染相关的肾小球肾炎，以及肝硬化、炎症性肠病、乳糜泻、感染（如病毒性肝炎）和自身免疫性疾病（如轴性脊柱炎）引起的继发性IgAN。根据肾脏疾病：改善全球结局2025年IgAN管理临床实践指南，蛋白尿超过每天0.5 g的患者的治疗包括行为改变(例如，饮食钠和lt；2 g/d，戒烟，控制体重，运动)，目标血压低于120/70 mm Hg的降压药物，以及减少含iga免疫复合物形成的治疗（例如，靶向释放布地奈德），减少肾小球损伤（例如，全身糖皮质激素，伊普他科潘），以及控制现有的igan诱导的肾素损失（例如，肾素-血管紧张素系统抑制剂或双重内皮素-血管紧张素受体拮抗剂）。斯巴sentan]单独或与钠-葡萄糖共转运蛋白2抑制剂联合使用)。IgAN是世界范围内免疫介导肾小球疾病的主要原因。疑似IgAN和蛋白尿大于或等于每天0.5 g的患者应进行肾活检以确认诊断。IgAN的治疗包括行为改变、血压管理和减少含有iga的免疫复合物形成的治疗（如靶向释放布地奈德）、减少免疫复合物介导的肾小球损伤（如全身糖皮质激素、伊普他科潘）和控制IgAN诱导的肾素损失（如肾素-血管紧张素系统抑制剂、双重内皮素-血管紧张素受体拮抗剂和钠-葡萄糖共转运蛋白2抑制剂）。
{"title":"IgA Nephropathy in Adults","authors":"Sinead Stoneman, Jia Wei Teh, Michelle Marie O’Shaughnessy","doi":"10.1001/jama.2025.25020","DOIUrl":"https://doi.org/10.1001/jama.2025.25020","url":null,"abstract":"Importance IgA nephropathy (IgAN) is a chronic kidney disease involving deposition of IgA-containing immune complexes in the glomerulus, causing glomerular inflammation and scarring. It is the most common immune-mediated glomerular disease worldwide, and affects an estimated 198 887 to 208 184 persons in the US. Up to 50% of patients with IgAN develop kidney failure within 10 years of diagnosis. Observations IgAN typically presents with nephritic syndrome and usually occurs in younger adults, with a mean age at diagnosis of 34 to 45 years. Incidence is highest in East Asia. Approximately 60% of cases are detected incidentally with hematuria or proteinuria on urinalysis. Up to 30% of patients present with episodic visible hematuria, often concomitantly with an upper respiratory or gastrointestinal tract infection (synpharyngitic hematuria). Less common presentations include nephrotic syndrome (&amp;lt;5%) and rapidly progressive glomerulonephritis (&amp;lt;5%). When IgAN is suspected (due to hematuria, proteinuria, or reduced kidney function), initial workup should include quantification of proteinuria and assessment for other causes of nephritic syndrome (eg, lupus nephritis). Adults with suspected IgAN and proteinuria greater than or equal to 0.5 g per day should undergo kidney biopsy. The diagnosis of primary IgAN is based on presence of IgA-dominant immune deposits in the glomerular mesangium after excluding other causes of this histologic appearance, ie, IgA vasculitis, IgA-dominant infection-related glomerulonephritis, and secondary IgAN from diseases such as cirrhosis, inflammatory bowel disease, celiac disease, infection (eg, viral hepatitis), and autoimmune diseases (eg, axial spondyloarthritis). Based on the Kidney Disease: Improving Global Outcomes 2025 clinical practice guideline for the management of IgAN, treatment for patients with proteinuria greater than 0.5 g per day includes behavioral modifications (eg, dietary sodium &amp;lt;2 g/d, smoking cessation, weight control, exercise), antihypertensive medications for goal blood pressure less than 120/70 mm Hg, and therapies to reduce the formation of IgA-containing immune complexes (eg, targeted-release budesonide), decrease glomerular injury (eg, systemic glucocorticoids, iptacopan), and manage existing IgAN-induced nephron loss (eg, renin-angiotensin system inhibitor or dual endothelin angiotensin receptor antagonist [eg, sparsentan] alone or in combination with a sodium-glucose cotransporter 2 inhibitor). Conclusions and Relevance IgAN is the leading cause of immune-mediated glomerular disease worldwide. Patients with suspected IgAN and proteinuria greater than or equal to 0.5 g per day should undergo kidney biopsy to confirm the diagnosis. Treatment of IgAN includes behavioral modifications, blood pressure management, and therapies to decrease formation of IgA-containing immune complexes (eg, targeted-release budesonide), reduce immune complex–mediated glomerular injur","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048287","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}
This Viewpoint discusses the Centers for Medicare &amp; Medicaid Services’ (CMS) Increasing Organ Transplant Access (IOTA) model and how its focus should be less on volume than patient-centered quality-of-life outcomes.
{"title":"Reimagining Transplant Center Incentives Beyond the CMS IOTA Model","authors":"Alex Chan, Alvin E. Roth","doi":"10.1001/jama.2025.26194","DOIUrl":"https://doi.org/10.1001/jama.2025.26194","url":null,"abstract":"This Viewpoint discusses the Centers for Medicare &amp;amp; Medicaid Services’ (CMS) Increasing Organ Transplant Access (IOTA) model and how its focus should be less on volume than patient-centered quality-of-life outcomes.","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"102 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048286","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}
This Perspective discusses the limitations of reliable assessment of consciousness in critically ill, behaviorally unresponsive patients in light of recent situations in which such patients exhibited signs of consciousness moments before initiation of organ recovery surgery.
{"title":"Consciousness and Controlled Donation After Circulatory Determination of Death","authors":"Michael J. Young, Christof Koch","doi":"10.1001/jama.2025.27045","DOIUrl":"https://doi.org/10.1001/jama.2025.27045","url":null,"abstract":"This Perspective discusses the limitations of reliable assessment of consciousness in critically ill, behaviorally unresponsive patients in light of recent situations in which such patients exhibited signs of consciousness moments before initiation of organ recovery surgery.","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048288","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":"Long-Term CVD Risk Associated With Very High Lipoprotein(a) Levels in Women.","authors":"Samantha Anderer","doi":"10.1001/jama.2025.23032","DOIUrl":"https://doi.org/10.1001/jama.2025.23032","url":null,"abstract":"","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021371","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":"Stress May Link Depression and Anxiety to Cardiovascular Disease.","authors":"Rita Rubin","doi":"10.1001/jama.2025.25865","DOIUrl":"https://doi.org/10.1001/jama.2025.25865","url":null,"abstract":"","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021367","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":"Decline in US Overdose Deaths May Be Tied to Fentanyl Disruption.","authors":"Samantha Anderer","doi":"10.1001/jama.2025.23028","DOIUrl":"https://doi.org/10.1001/jama.2025.23028","url":null,"abstract":"","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021363","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":"Limited Evidence Supporting Melatonin Use in Most Children.","authors":"Samantha Anderer","doi":"10.1001/jama.2025.23029","DOIUrl":"https://doi.org/10.1001/jama.2025.23029","url":null,"abstract":"","PeriodicalId":518009,"journal":{"name":"JAMA","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021365","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}
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