tbuckley/cabot-search huggingface dataset:
Clinical and Molecular Characteristics of High-Risk, Recurrent, or Metastatic Endometrial Cancer That Is Human Epidermal Growth Factor Receptor 2–Low
Authors: Dione van Dijk, Lisa Vermij, Alicia León-Castillo, Melanie Powell, Jan Jobsen, Alexandra Leary, David Bowes, Linda Mileshkin, Catherine Genestie, Ina Jürgenliemk-Schulz, Cor de Kroon, Cathelijne Post, Stephanie de Boer, Linda Nooij, Judith Kroep, Carien Creutzberg, Vincent Smit, Nanda Horeweg, Tjalling Bosse, Anneke Westermann
Journal: Journal of Clinical Oncology (2024)

PURPOSE Recent success of human epidermal growth factor receptor 2 (HER2)–targeted antibody-drug-conjugate trastuzumab-deruxtecan in HER2-low and HER2-positive tumors has sparked interest in examining the HER2 status of tumors not traditionally associated with HER2 amplification. Despite the increasing number of systemic treatment options, patients with advanced endometrial cancer (EC) still face a poor prognosis. This study evaluates HER2-low status in over 800 EC, correlating HER2 with both molecular and clinical features. METHODS HER2 status was determined by immunohistochemistry (IHC) and dual in situ hybridization (DISH) on four studies of previously classified high-risk EC (PORTEC-3 and Medical Spectrum Twente cohort), recurrent or metastatic EC (DOMEC), and a primary stage IV cohort. EC was classified as HER2-negative (IHC 0), HER2-low (IHC 1+/2+ without amplification), or HER2-positive (IHC 3+ or DISH-confirmed amplification). Survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models assessed the independence of any prognostic impact of HER2 status. RESULTS HER2 status was determined in 806 EC: 74.8% were HER2-negative, 17.2% HER2-low, and 7.9% HER2-positive. HER2-low was found across all molecular classes and histotypes. The highest rates of HER2-low and HER2-positive tumors were in recurrent or metastatic EC (35.6% and 15.6%), followed by primary stage IV EC (29.9% and 12.4%) and high-risk EC (14.2% and 6.8%). HER2 status had no independent prognostic value. CONCLUSION A quarter of high-risk, metastatic, or recurrent EC exhibited HER2 overexpression. The presence of HER2 overexpression in all clinical and molecular categories highlights the need for broad testing and offers treatment options for a wide range of patients.
Thoracic Radiotherapy Improves the Survival in Patients With <i>EGFR</i> -Mutated Oligo-Organ Metastatic Non–Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitors: A Multicenter, Randomized, Controlled, Phase III Trial
Authors: Hongfu Sun, Minghao Li, Wei Huang, Jian Zhang, Shihong Wei, Yongjing Yang, Zhongtang Wang, Shucheng Ye, Heyi Gong, Yaowen Zhang, Jie Li, Haixia Song, Lifang Wang, Xiangming Chen, Haiqun Lin, Gaofeng Ding, Hongwei Li, Anping Zheng, Xuezhen Ma, ShaoShui Chen, Liping Liu, Kaixian Zhang, Chengrui Fu, Wenzhi Liu, Jing Wang, Xiaqin Zhang, Tingting Liu, Dan Han, Qian Zhao, Peipei Wu, Qianqian Yuan, LiJun Tian, Ping Zhang, Xueqin Wu, Fei Chen, Zicheng Zhang, Baosheng Li
Journal: Journal of Clinical Oncology (2024)

PURPOSE This multicenter, randomized, phase III clinical trial (Northern Radiation Oncology Group of China-002) focused on patients with oligo-organ metastatic non–small cell lung cancer (NSCLC) who have epidermal growth factor receptor ( EGFR ) mutations. We aimed to investigate whether first-line concurrent thoracic radiotherapy (TRT) and EGFR-tyrosine kinase inhibitors (TKIs), compared with TKIs alone, could achieve better survival. MATERIALS AND METHODS The patients in the TKI plus TRT group received 60 Gy to primary lung tumor and positive regional lymph nodes. Radiotherapy for metastases to other sites was determined by clinicians. The primary end point was the progression-free survival (PFS). Secondary end points included overall survival (OS) and treatment-related adverse events (TRAEs). The first and second interim analyses were performed in March 2021 and March 2022. RESULTS Between April 14, 2016, and February 25, 2022, a total of 118 patients were enrolled. Compared with the TKI alone group, the TKI plus TRT group achieved significantly better PFS (hazard ratio [HR], 0.57; P = .004) and OS (HR, 0.62; P = .029). The median PFS was 10.6 months in the TKI alone group and 17.1 months in the TKI plus TRT group. The median OS was 26.2 months and 34.4 months in the TKI alone group and TKI plus TRT group, respectively. The TKI plus TRT group showed better local control but was associated with a higher incidence of severe TRAEs (11.9% v 5.1%). CONCLUSION For patients with EGFR -mutated oligo-organ metastatic NSCLC treated with first-line EGFR-TKIs, concurrent TRT improves the PFS and OS, and TRAEs are acceptable and tolerable.
Screening chronic kidney disease through deep learning utilizing ultra-wide-field fundus images
Authors: Xinyu Zhao, Xingwang Gu, Lihui Meng, Yongwei Chen, Qing Zhao, Shiyu Cheng, Wenfei Zhang, Tiantian Cheng, Chuting Wang, Zhengming Shi, Shengyin Jiao, Changlong Jiang, Guofang Jiao, Da Teng, Xiaolei Sun, Bilei Zhang, Yakun Li, Huiqin Lu, Changzheng Chen, Hao Zhang, Ling Yuan, Chang Su, Han Zhang, Song Xia, Anyi Liang, Mengda Li, Dan Zhu, Meirong Xue, Dawei Sun, Qiuming Li, Ziwu Zhang, Donglei Zhang, Hongbin Lv, Rishet Ahmat, Zilong Wang, Charumathi Sabanayagam, Xiaowei Ding, Tien Yin Wong, Youxin Chen
Journal: npj Digital Medicine (2024)

To address challenges in screening for chronic kidney disease (CKD), we devised a deep learning-based CKD screening model named UWF-CKDS. It utilizes ultra-wide-field (UWF) fundus images to predict the presence of CKD. We validated the model with data from 23 tertiary hospitals across China. Retinal vessels and retinal microvascular parameters (RMPs) were extracted to enhance model interpretability, which revealed a significant correlation between renal function and RMPs. UWF-CKDS, utilizing UWF images, RMPs, and relevant medical history, can accurately determine CKD status. Importantly, UWF-CKDS exhibited superior performance compared to CTR-CKDS, a model developed using the central region (CTR) cropped from UWF images, underscoring the contribution of the peripheral retina in predicting renal function. The study presents UWF-CKDS as a highly implementable method for large-scale and accurate CKD screening at the population level.
MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma
Authors: Sara Mato, Natalia Castrejón-de-Anta, Ariadna Colmenero, Lorenzo Carità, Julia Salmerón-Villalobos, Joan Enric Ramis-Zaldivar, Ferran Nadeu, Noelia Garcia, Luojun Wang, Jaime Verdú-Amorós, Mara Andrés, Nuria Conde, Verónica Celis, Maria José Ortega, Ana Galera, Itziar Astigarraga, Vanesa Perez-Alonso, Eduardo Quiroga, Aixiang Jiang, David W. Scott, Elias Campo, Olga Balagué, Itziar Salaverria
Journal: Blood Cancer Journal (2024)

Aggressive B-cell non-Hodgkin lymphomas (NHL) in children, adolescents, and young adults (CAYA) include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and a subset of high-grade tumors with features intermediate between these entities whose genetic and molecular profiles have not been completely elucidated. In this study, we have characterized 37 aggressive B-NHL in CAYA, 33 with high-grade morphology, and 4 DLBCL with MYC rearrangement (MYC-R), using targeted next-generation sequencing and the aggressive lymphoma gene expression germinal center B-cell-like (GCB), activated B-cell-like (ABC), and dark zone signatures (DZsig). Twenty-two tumors had MYC-R without BCL2 breaks, and two MYC-non-R cases had BCL6 translocations. MYC-R cases, including DLBCL, carried BL-related mutations and copy number alterations. Conversely, MYC-non-R lymphomas had alterations in the B-cell receptor signaling/NF-κB pathway (71%). DZsig was expressed in 12/13 of MYC-R tumors but only in 2/10 of MYC-non-R GCB tumors (P < 0.001). The 3-year event-free survival (EFS) of the whole cohort was 79.6%. TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL.
Cardiac tumour necrosis factor receptor-associated factor 7 mediates the ubiquitination of apoptosis signal-regulating kinase 1 and aggravates cardiac hypertrophy
Authors: Yan Che, Yu-Ting Liu, Zhao-Peng Wang, Yi-Zhou Feng, Hong-Xia Xia, Yuan Yuan, Heng Zhou, Hong-Liang Qiu, Man-Li Hu, Sha-Sha Wang, Qi-Zhu Tang
Journal: Cardiovascular Research (2024)

Abstract Aims Cardiac remodelling is a common pathophysiological process in the development of various cardiovascular diseases, but there is still a lack of effective interventions. Tumour necrosis receptor-associated factor 7 (TRAF7) belongs to the tumour necrosis factor receptor-associated factor family and plays an important role in biological processes. Previous studies have shown that TRAF7 mutations lead to congenital defects and malformations of the heart. However, the molecular mechanisms of TRAF7 in the underlying pathogenesis of pathological cardiac hypertrophy remain unknown. We aim to study the molecular mechanisms and effects of TRAF7 in cardiac remodelling and whether it has the potential to become a therapeutic target for cardiac remodelling. Methods and results The pressure overload–induced cardiac hypertrophy model in mice was established via transverse aortic constriction (TAC) surgery, and cardiomyocytes were treated with phenylephrine (PE) to induce hypertrophic phenotype. Levels of cardiac dysfunction and remodelling were measured with echocardiography and tissue or cell staining. RNA sequencing, western blot, qRT–PCR, co-immunoprecipitation, and in vivo ubiquitination assays were used to explore the molecular mechanisms. The results showed that the expression of TRAF7 increased gradually during the development of hypertrophy. Accordingly, TRAF7 significantly exacerbated the PE-induced enlargement of primary neonatal Sprague-Dawley rat cardiomyocytes, whereas TRAF7 knockdown alleviated the hypertrophic phenotype in primary cardiomyocytes. Cardiac-specific overexpression of TRAF7 accelerated hypertrophic phenotype in mice and cardiac-specific Traf7 conditional knockout mice improved hypertrophic phenotype induced by TAC. Mechanistically, TRAF7 directly interacted with apoptosis signal-regulating kinase-1 (ASK1) and promoted ASK1 phosphorylation by mediating the K63-linked ubiquitination of ASK1 in response to PE stimulation, which then promoted ASK1 activation and downstream signalling during cardiac hypertrophy. Notably, the pro-hypertrophic effect of TRAF7 was largely blocked by GS4997 in vitro and cardiac-specific Ask1 conditional knockout in vivo. Conclusion In summary, we identified TRAF7 as an essential regulator during cardiac hypertrophy, and modulation of the regulatory axis between TRAF7 and ASK1 could be a novel therapeutic strategy to prevent this pathological process.
Childhood and adolescent essential thrombocythemia and prefibrotic primary myelofibrosis: insights into diagnosis, outcomes, and treatment from a large Chinese cohort
Authors: Rongfeng Fu, Huan Dong, Wenjing Gu, Ke Meng, Ting Sun, Xiaofan Liu, Xinmiao Qu, Jia Chen, Feng Xue, Wei Liu, Yunfei Chen, Mankai Ju, Xinyue Dai, Ying Chi, Wentian Wang, Xiaolei Pei, Xiaofan Zhu, Renchi Yang, Huiyuan Li, Lei Zhang
Journal: Leukemia (2024)
Implementing a national programme of pathogen genomics for public health: the Australian Pathogen Genomics Program (AusPathoGen)
Authors: Jessica R Webb, Patiyan Andersson, Eby Sim, Alireza Zahedi, Angela Donald, Tuyet Hoang, Anne E Watt, Jessica E Agius, Celeste M Donato, Max L Cummins, Tehzeeb Zulfiqar, Son Nghiem, Chantel Lin, Dimitrios Menouhos, Lex E X Leong, Rob Baird, Karina Kennedy, Louise Cooley, David Speers, Chuan Kok Lim, Joep de Ligt, Angeline Ferdinand, Katie Glass, Martyn D Kirk, Steven P Djordjevic, Clare Sloggett, Kristy Horan, Torsten Seemann, Vitali Sintchenko, Amy V Jennison, Benjamin P Howden
Journal: The Lancet Microbe (2024)
Dose-escalated Adaptive Radiotherapy for Bladder Cancer: Results of the Phase 2 RAIDER Randomised Controlled Trial
Authors: Robert Huddart, Shaista Hafeez, Clare Griffin, Ananya Choudhury, Farshad Foroudi, Isabel Syndikus, Benjamin Hindson, Amanda Webster, Helen McNair, Alison Birtle, Mohini Varughese, Ann Henry, Duncan B McLaren, Omi Parikh, Ashok Nikapota, Colin Tang, Emma Patel, Elizabeth Miles, Karole Warren-Oseni, Tomas Kron, Courtney Hill, Lara Philipps, Catalina Vassallo-Bonner, Ka Ching Cheung, Hannah Gribble, Rebecca Lewis, Emma Hall
Journal: European Urology (2024)

Delivering radiotherapy to the bladder is challenging as it is a mobile, deformable structure. Dose-escalated adaptive image-guided radiotherapy could improve outcomes. RAIDER aimed to demonstrate the safety of such a schedule.
Validation of the Real-World Application of the Hidradenitis Suppurativa Quality of Life (HiSQOL) Score to Adults with Hidradenitis Suppurativa
Authors: Amit Garg, Russel Burge, Andrea Cohee, Hayley Wallinger, Isabel Truman, Aaron Keal, Andrew Strunk, Sophie Barlow
Journal: British Journal of Dermatology (2024)

Abstract Background Hidradenitis suppurativa (HS) has unique symptoms and physical features among skin diseases. Patient reported outcome measures (PROMs) agnostic to specific skin diseases may not fully characterise the influence of HS on quality of life (QoL). A HS-specific PROM is needed to capture the impact of HS on QoL in the real-world setting. Objective To validate the Hidradenitis Suppurativa Quality of Life Questionnaire (HiSQOL) as a HS-specific PROM by comparing it to the Dermatology Life Quality Index (DLQI) in clinical practice. Methods Data were drawn from the Adelphi HS Disease Specific Programme™, a cross-sectional survey of physicians and patients conducted in France, Germany, Italy, Spain, and the United States between November, 2020 and April, 2021. Practicing physicians each provided demographic and clinical data for 5–7 consecutively evaluated HS patients aged at least 10 years receiving any treatment for HS, and an additional 3 patients undergoing biologic treatment; only patients aged at least 18 years were included in this study. Patients completed the DLQI and HiSQOL. Construct validity was assessed by Pearson’s correlation between DLQI and HiSQOL scores. The HiSQOL item discrimination was assessed by comparing differences in item responses between the highest and lowest 25% of HiSQOL scores. Multivariable linear regressions assessed relationships between individual PROM item responses and the total score of the other PROM. Results In total, 677 patients [mean age of 34.3 (11.3) years; female (57.3%, n=388)] completed both the HiSQOL and DLQI. There was strong correlation between HiSQOL and DLQI total scores (Pearson’s correlation 0.87 [95% confidence interval: 0.85-0.89, p&amp;lt;0.001]). The HiSQOL items that had the biggest impact on QoL related to “Embarrassment”, “Depression” and “Anxiety”, items that also had among the lowest relationship to total DLQI score. Conclusions The HiSQOL is a valid tool for assessing QoL in HS patients in the real-world setting. Furthermore, the HiSQOL better captures those aspects of HS that have the highest impact on QoL, including depression and anxiety, which are not captured by the DLQI.
Intra-rater agreement of lesion counts in hidradenitis suppurativa
Authors: Bria Midgette, Andrew Strunk, Amit Garg
Journal: British Journal of Dermatology (2024)

The heterogeneous presentation of hidradenitis suppurativa (HS) lesions can result in variation in clinical trial outcome assessments when performed by the same rater as well as different raters. In the PIONEER I and II trials of patients with HS, there was substantial disagreement between repeated lesion counts by the same rater during a time period in which little true change is expected. Standardization of lesion classification and improved rater training are critical for advancing HS drug development.
New WHO guidelines for treating rhodesiense human African trypanosomiasis: expanded indications for fexinidazole and pentamidine
Authors: Andreas K Lindner, Veerle Lejon, Michael P Barrett, Lucille Blumberg, Salome A Bukachi, Rebecca J Chancey, Andrew Edielu, Lucas Matemba, Tihitina Mesha, Victor Mwanakasale, Christopher Pasi, Tapunda Phiri, Jorge Seixas, Elie A Akl, Katrin Probyn, Gemma Villanueva, Pere P Simarro, Augustin Kadima Ebeja, Jose R Franco, Gerardo Priotto
Journal: The Lancet Infectious Diseases (2024)
Sex-specific Genetic Determinants of Right Ventricular Structure and Function
Authors: Lars Harbaum, Jan K. Hennigs, Julian Pott, Jonna Ostermann, Christoph R. Sinning, Arunashis Sau, Ewa Sieliwonczyk, Fu Siong Ng, Christopher J. Rhodes, Khodr Tello, Hans Klose, Stefan Gräf, Martin R Wilkins
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

While sex differences in right heart phenotypes have been observed, the molecular drivers remain unknown.
Aztreonam–avibactam versus meropenem for the treatment of serious infections caused by Gram-negative bacteria (REVISIT): a descriptive, multinational, open-label, phase 3, randomised trial
Authors: Yehuda Carmeli, José Miguel Cisneros, Mical Paul, George L Daikos, Minggui Wang, Julian Torre-Cisneros, George Singer, Ivan Titov, Illia Gumenchuk, Yongjie Zhao, Rosa-María Jiménez-Rodríguez, Lu Liang, Gang Chen, Oleksandr Pyptiuk, Firdevs Aksoy, Halley Rogers, Michele Wible, Francis F Arhin, Alison Luckey, Joanne L Leaney, Rienk Pypstra, Joseph W Chow, Marc Bonten, Jesús Rodríguez-Baño, Christine Lammens, Herman Goossens, Surbhi Malhotra-Kumar
Journal: The Lancet Infectious Diseases (2024)
12-month persistence of immune responses to self-amplifying mRNA COVID-19 vaccines: ARCT-154 versus BNT162b2 vaccine
Authors: Yoshiaki Oda, Yuji Kumagai, Manabu Kanai, Yasuhiro Iwama, Iori Okura, Takeshi Minamida, Yukihiro Yagi, Toru Kurosawa, Pad Chivukula, Ye Zhang, Judd L Walson
Journal: The Lancet Infectious Diseases (2024)
Safety, immunogenicity, and optimal dosing of a modified vaccinia Ankara-based vaccine against MERS-CoV in healthy adults: a phase 1b, double-blind, randomised placebo-controlled clinical trial
Authors: Matthijs P Raadsen, Christine Dahlke, Anahita Fathi, Svenja Hardtke, Michael Klüver, Verena Krähling, Gesche K Gerresheim, Leonie Mayer, Anna Z Mykytyn, Leonie M Weskamm, Tamara Zoran, Eric C M van Gorp, Gerd Sutter, Stephan Becker, Bart L Haagmans, Marylyn M Addo
Journal: The Lancet Infectious Diseases (2024)
Transcriptomic markers of biological aging in breast cancer survivors: a longitudinal study
Authors: Judith E Carroll, Catherine M Crespi, Steve Cole, Patricia A Ganz, Laura Petersen, Julienne E Bower
Journal: JNCI Journal of the National Cancer Institute (2024)

The purpose of this study was to examine the impact of breast cancer therapy on biological aging as measured by expression of genes for cellular senescence (p16INK4a, SenMayo), DNA damage response, and proinflammatory senescence-associated secretory phenotype.
Follicular lymphoma comprises germinal center-like and memory-like molecular subtypes with prognostic significance
Authors: Camille Laurent, Preeti Trisal, Bruno Tesson, Sahil Seth, Alicia Beyou, Sandrine Roulland, Bastien Lesne, Nathalie Van Acker, Juan Pablo Cerapio, Loïc Chartier, Arnaud Guille, Matthew E Stokes, Chris C Huang, Sarah Huet, Anita Krithivas Gandhi, Franck Morschhauser, Luc Xerri
Journal: Blood (2024)
HIV Reservoir Landscape in Breast Milk From Long-Term Virally Suppressed Individuals
Authors: Ariel Osegueda, Lucia Baquero, Andrea Pereyra Casanova, Leonel Cruces, Katie Fisher, Cintia Mendez, Yanina Ghiglione, Sarah Palmer, Gabriela Turk, Natalia Laufer
Journal: Annals of Internal Medicine (2024)
Abortion
Authors: Cynthia H. Chuang, Sarah Horvath
Journal: Annals of Internal Medicine (2024)

Induced abortion is safe, is common, and reduces pregnancy-related maternal morbidity and mortality. Internal medicine physicians are uniquely positioned to counsel patients on their pregnancy options, assess medical risks of pregnancy in the context of comorbidities, refer for abortion care when the patient desires it, or provide abortion care themselves. Clinicians can also provide anticipatory guidance about what patients should expect if they seek abortion care.
Asciminib plus dasatinib and prednisone for Philadelphia chromosome-positive acute leukemia
Authors: Marlise R. Luskin, Mark Alan Murakami, Julia H. Keating, Yael Flamand, Eric S Winer, Jacqueline S. Garcia, Maximilian Stahl, Richard M. Stone, Martha Wadleigh, Stella Louise Jaeckle, Ella Hagopian, David M. Weinstock, Jessica Liegel, Malgorzata McMasters, Eunice S Wang, Wendy Stock, Daniel J DeAngelo
Journal: Blood (2024)
Cost-effectiveness of iptacopan for paroxysmal nocturnal hemoglobinuria
Authors: Satoko Ito, Karthik Chetlapalli, Daniel Wang, Kunal C Potnis, Rhys Richmond, Harlan Krumholz, Alfred I Lee, Adam Cuker, George Goshua
Journal: Blood (2024)

Iptacopan, a novel oral Factor B inhibitor, recently obtained FDA approval for treating paroxysmal nocturnal hemoglobinuria, a rare blood disorder characterized by persistent complement-mediated hemolytic anemia. The standard-of-care (SOC) has traditionally relied on complement C5 inhibitors eculizumab and ravulizumab, which are limited by persistent anemia from extravascular hemolysis and requirement for intravenous infusion. Recent publication of phase 3 studies in this arena reinforces iptacopan as an effective anti-complement monotherapy compared with SOC. Given ongoing price negotiations and limited literature showing its cost-ineffectiveness in the anti-C5-treated population, we conducted a comprehensive cost-effectiveness analysis of iptacopan monotherapy in anti-C5-treated patients from the societal perspective, as compared to C5 inhibition. The primary outcomes were the incremental net monetary benefit (iNMB) across a lifetime horizon and the cost-effective maximum monthly threshold price of iptacopan monotherapy compared to the SOC. The secondary outcome was time saved for patients and nurses with the utilization of oral iptacopan therapy. Iptacopan monotherapy and SOC accrued 12.6 and 10.8 QALYs at costs of $9.52 million and $13.5 million, respectively. Iptacopan remained cost-saving across extensive sensitivity and all scenario analyses, including alternative parameterization for anemia resolution and aggregated individual-level utilities and transition probability matrix. Across all probabilistic sensitivity analyses, iptacopan therapy was favored over SOC in 100% of 10,000 Monte Carlo iterations. Cost-saving thresholds for iptacopan versus anti-C5 in are ~1.1, 1.4, and 1.4 in Brazil, Japan, and the United States. Iptacopan monotherapy can improve quality-adjusted life expectancy for patients while saving healthcare costs across jurisdictions.
Modernizing Medical Device Regulation: Challenges and Opportunities for the 510(k) Clearance Process
Authors: Kushal T. Kadakia, Vinay K. Rathi, Sanket S. Dhruva, Joseph S. Ross, Harlan M. Krumholz
Journal: Annals of Internal Medicine (2024)

Nearly all medical devices reviewed by the U.S. Food and Drug Administration (FDA) are authorized via the 510(k) clearance process. Established in 1976, this review pathway bases authorizations on the comparability of new devices to previously authorized devices ("predicates"). This evaluation usually does not require clinical evidence of safety and effectiveness. Advocates of the 510(k) clearance process tout its support for device innovation and rapid market access, and critics of the 510(k) clearance process express that it may inadequately protect patient safety. In September 2023, the FDA issued 3 guidance documents that, if finalized, would significantly change medical device regulation. This article provides clinical and regulatory context for the proposed guidance documents, which focus on predicate selection, clinical testing requirements, and implantable devices, and identifies opportunities for further reforms that promote transparency and patient safety.