tbuckley/cabot-search huggingface dataset:
Gender and Career Milestones of Mid-Career to Senior Medical Faculty Who Held Career Development Awards
Authors: Eve A. Kerr, Kent A. Griffith, Rochelle D. Jones, Christina M. Cutter, Eva L. Feldman, Kelly C. Paradis, Isis H. Settles, Kanakadurga Singer, Nancy D. Spector, Abigail J. Stewart, Dana A. Telem, Peter A. Ubel, Reshma Jagsi
Journal: JAMA Internal Medicine (2025)

This survey study examines attainment of professional and leadership milestones by middle to senior career women and men 12 to 15 years after receiving K awards.
Antibiotic Treatment in Patients Hospitalized for Nonsevere COVID-19
Authors: Michael S. Pulia, Meggie Griffin, Rebecca Schwei, Aurora Pop-Vicas, Lucas T. Schulz, Meng-Shiou Shieh, Penelope Pekow, Valerie M. Vaughn, Peter K. Lindenauer
Journal: JAMA Network Open (2025)

Importance Patients hospitalized with nonsevere COVID-19 continue to receive community-acquired pneumonia (CAP) antibiotic treatment despite a low risk of bacterial coinfection. Unnecessary antibiotic prescribing contributes to global antibiotic resistance and also poses a threat to individual patients. Objective To examine the association of CAP antibiotic treatment started on admission with clinical outcomes among a large sample of patients hospitalized for nonsevere COVID-19 in hospitals across the US. Design, Setting, and Participants This retrospective cohort study used a target trial emulation design. Participants were adult, immunocompetent patients admitted to general care for COVID-19 from April 2020 to December 2023 at 1053 US-based acute-care hospitals that contribute data to the Premier Healthcare Database. Patients with nonpneumonia bacterial infections present on admission were excluded. Data were analyzed from April to October 2024. Exposure Receipt of a CAP antibiotic regimen on the day of admission. Main Outcomes and Measures The primary outcome was a composite measure of deterioration (vasopressor, high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, intermediate care, intensive care unit admission) and in-hospital mortality occurring on day 2 or later. The association between receipt of antibiotic therapy and the primary outcome was assessed using propensity methods while adjusting for a broad set of potential confounders, including cotreatments. Results The cohort included 520 405 patients with COVID-19 (median [IQR] age, 66 [53-78] years; 266 186 [51.2%] male), including 92 708 Black patients (17.8%), 63 619 Hispanic patients (12.2%), and 304 649 White patients (58.5%); 279 656 patients (53.7%) had Medicare insurance. A total of 160 482 patients (30.8%) were treated with a CAP antibiotic regimen on day 1 of admission. The primary composite outcome was higher in the CAP group (20.8%) compared with the unexposed (no antibiotic) group (18.4%), but the difference did not meet the predefined criteria for clinical significance (ASD, 4.1%). Patients who received CAP antibiotics had higher odds of poor clinical outcomes (propensity matched–odds ratio [OR], 1.03 [95% CI, 1.01-1.05]; P = .003; inverse probability treatment weighted–OR, 1.03 [95% CI, 1.02-1.05]; P &amp;amp;lt; .001; standardized mortality ratio weighted–OR, 1.10 [95% CI, 1.08-1.12]; P &amp;amp;lt; .001). Conclusions and Relevance In this large cohort study of patients hospitalized with nonsevere COVID-19, there was no clinically meaningful difference in outcomes with early antibiotic treatment. Given the risks associated with unnecessary antibiotic treatment, these results argue against routine antibiotic use in this population.
Engineered CRO-CD7 CAR-NK cells derived from pluripotent stem cells avoid fratricide and efficiently suppress human T-cell malignancies
Authors: Yunqing Lin, Ziyun Xiao, Fangxiao Hu, Xiujuan Zheng, Chenyuan Zhang, Yao Wang, Yanhong Liu, Dehao Huang, Zhiqian Wang, Chengxiang Xia, Qitong Weng, Leqiang Zhang, Yaoqin Zhao, Hanmeng Qi, Yiyuan Shen, Yi Chen, Fan Zhang, Jiaxin Wu, Pengcheng Liu, Jiacheng Xu, Lijuan Liu, Yanping Zhu, Jingliao Zhang, Wenbin Qian, Aibin Liang, Xiaofan Zhu, Tongjie Wang, Mengyun Zhang, Jinyong Wang
Journal: Journal of Hematology & Oncology (2025)

T-cell malignancies are highly aggressive hematological tumors with limited effective treatment options. CAR-NK cell therapy targeting CD7 has emerged as a promising approach for treating T-cell malignancies. However, conventional CAR-NK cell therapy faces the challenges of cell fratricide due to CD7 expression on both malignant cells and normal NK cells. Additionally, engineering CARs into human tissue-derived NK cells demonstrates heterogeneity, low transduction efficiency, and high manufacturing costs. The human pluripotent stem cells (hPSCs) were genetically modified by knocking out the CD7 gene and introducing the CD7 CAR expression cassette to generate CD7 KO-CD7 CAR-hPSCs. These modified hPSCs were subsequently differentiated into CD7 KO-CD7 CAR-iNK cells using an efficient organoid induction method. The cytotoxicity of CD7 KO-CD7 CAR-iNK cells against CD7+ tumor cells was evaluated. Furthermore, we overexpressed the CXCR4 gene in CD7 KO-CD7 CAR-hPSCs and derived CXCR4-expressing CD7 KO-CD7 CAR-iNK (CRO-CD7 CAR-iNK) cells. The dynamics of CRO-CD7 CAR-iNK cells in vivo were tracked, and their therapeutic efficacy was assessed using human T-cell acute lymphoblastic leukemia (T-ALL) xenograft models. The CD7 KO-CD7 CAR-iNK cells derived from CD7 KO-CD7 CAR-hPSCs effectively avoided fratricide, demonstrated normal expansion, and exhibited potent and specific anti-tumor activity against CD7+ T-cell tumor cell lines and primary T-ALL cells. CXCR4 overexpression in CRO-CD7 CAR-iNK cells improved their homing capacity and extended their persistence in vivo. The CRO-CD7 CAR-iNK cells significantly suppressed tumor growth and prolonged the survival of T-ALL tumor-bearing mice. Our study provides a reliable strategy for the large-scale generation of fratricide-resistant CD7 CAR-iNK cells with robust anti-tumor effects from hPSCs, offering a promising cell product to treat T-cell malignancies.
Health-related quality of life in patients undergoing laparoscopic versus open hemihepatectomy: a secondary analysis of the ORANGE II PLUS randomised controlled, phase 3, superiority trial
Authors: Bram Olij, Robert S. Fichtinger, Luca A. Aldrighetti, Mohammad Abu Hilal, Roberto I. Troisi, Robert P. Sutcliffe, Marc G. Besselink, Somaiah Aroori, Krishna V. Menon, Bjørn Edwin, Mathieu D’Hondt, Valerio Lucidi, Tom F. Ulmer, Rafael Díaz-Nieto, Zahir Soonawalla, Steve White, Gregory Sergeant, Francesca Ratti, Christoph Kuemmerli, Vincenzo Scuderi, Frederik Berrevoet, Aude Vanlander, Ravi Marudanayagam, Pieter J. Tanis, Maxime J.L. Dewulf, Zina B. Eminton, Ulf P. Neumann, Lloyd Brandts, Siân A. Pugh, Åsmund A. Fretland, Merel L. Kimman, John N. Primrose, Ronald M. van Dam, Ronald M. Van Dam, Luca A. Aldrighetti, Mohammed Abu Hilal, Roberto I. Troisi, Robert P. Sutcliffe, Marc G. Besselink, Somaiah Aroori, Krishna V. Menon, Bjørn Edwin, Mathieu D’Hondt, Valerio Lucidi, Tom F. Ulmer, Rafael Diaz-Nieto, Zahir Soonawalla, Steve White, Gregory Sergeant, Robert S. Fichtinger, Bram Olij, Francesca Ratti, Christoph Kuemmerli, Vincenzo Scuderi, Frederik Berrevoet, Aude Vanlander, Ravi Marudanayagam, Pieter J. Tanis, Maxime J.L. Dewulf, Zina B. Eminton, Ulf P. Neumann, Lloyd Brandts, Siân A. Pugh, Åsmund A. Fretland, Merel L. Kimman, John N. Primrose, Remon Korenblik, Michelle Lintforth, Burak Gorçek, Penelope Rogers, Viviane Van Laethem, Betsy Van Loo, Kathleen Segers, Celine Demeyere, Ane Zamalloa, Cornelis Dejong, Davit Aghayan, Katherine Gordon-Quayle, Tracy Ward, Jess Boxal, Beth Wedge
Journal: The Lancet Regional Health - Europe (2025)
Deep Gaussian process with uncertainty estimation for microsatellite instability and immunotherapy response prediction from histology
Authors: Sunho Park, Morgan F Pettigrew, Yoon Jin Cha, In-Ho Kim, Minji Kim, Imon Banerjee, Isabel Barnfather, Jean R Clemenceau, Inyeop Jang, Hyunki Kim, Younghoon Kim, Rish K Pai, Jeong Hwan Park, N Jewel Samadder, Kyo Young Song, Ji-Youn Sung, Jae-Ho Cheong, Jeonghyun Kang, Sung Hak Lee, Sam C Wang, Tae Hyun Hwang
Journal: npj Digital Medicine (2025)

Determining tumor microsatellite status has significant clinical value because tumors that are microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) respond well to immune checkpoint inhibitors (ICIs) and oftentimes not to chemotherapeutics. We propose MSI-SEER, a deep Gaussian process-based Bayesian model that analyzes H&E whole-slide images in weakly-supervised-learning to predict microsatellite status in gastric and colorectal cancers. We performed extensive validation using multiple large datasets comprised of patients from diverse racial backgrounds. MSI-SEER achieved state-of-the-art performance with MSI prediction by integrating uncertainty prediction. We achieved high accuracy for predicting ICI responsiveness by combining tumor MSI status with stroma-to-tumor ratio. Finally, MSI-SEER's tile-level predictions revealed novel insights into the role of spatial distribution of MSI-H regions in the tumor microenvironment and ICI response.
Overall Survival and the Evolving Benefit-Risk Assessment for Poly (ADP-ribose) Polymerase Inhibitors in Advanced Ovarian Cancer
Authors: Mirat Shah, Ting-Yu Chen, Gwynn Ison, Mallorie H. Fiero, Hui Zhang, Xin Gao, Marc Neilson, Kirsten B. Goldberg, Abhilasha Nair, Tiffany K. Ricks, William F. Pierce, Nicole Gormley, Marc R. Theoret, Shenghui Tang, Richard Pazdur, Paul G. Kluetz, Laleh Amiri-Kordestani
Journal: Journal of Clinical Oncology (2025)

From 2014 through 2019, the US Food and Drug Administration (FDA) granted approval to six indications for poly (ADP-ribose) polymerase (PARP) inhibitors in advanced epithelial ovarian cancer (EOC). From 2022 through 2023, these six indications were withdrawn or narrowed after observation of a potential detrimental effect on overall survival (OS) in four randomized controlled trials. The indications for niraparib, olaparib, and rucaparib for the treatment of BRCA -mutated or homologous recombination deficiency–positive advanced EOC were withdrawn. The indications for niraparib, olaparib, and rucaparib for the maintenance treatment of recurrent EOC were narrowed to only patients with BRCA mutations. Recognizing the clinical implications of these regulatory actions, herein we describe the FDA's decision-making process and the rationale behind the removal or narrowing of these indications for PARP inhibitors in advanced EOC. Furthermore, this article provides insight into the FDA's interpretation of potential OS detriments and subgroup analyses to shape regulatory decisions.
Moderate- to Long-Term Effect of Dietary Interventions for Depression and Anxiety
Authors: Eman Abukmail, Neeraj Koloth Pradeep, Samantha Ahmed, Loai Albarqouni
Journal: Annals of Internal Medicine (2025)

Dietary interventions are a potential alternative treatment of depression and anxiety. To evaluate the effects of dietary interventions on depression and anxiety. PubMed, Cochrane CENTRAL, EMBASE, CINAHL, and PsycINFO searched from inception until 12 December 2024. Trial registries and forward and backward citation analysis done on 3 January 2025. Randomized controlled trials (RCTs) evaluated the effect of dietary advice with or without food provision compared with no specific dietary advice or active interventions for 3 months or longer on depression and/or anxiety. Two authors independently screened articles, extracted data, and assessed risk of bias. Primary outcomes included depression and anxiety symptoms at 3 months or longer. Random-effects meta-analyses were done, and the certainty of evidence was assessed. Twenty-five RCTs were included. Compared with no specific dietary advice, depressive symptoms might be improved in adults with elevated cardiometabolic risk by dietary advice on calorie restriction (standardized mean difference [SMD], -0.23 [95% CI, -0.38 to -0.09]; low certainty). Low-fat diets may also have very small effects on depressive symptoms in adults with elevated cardiometabolic risk (SMD, -0.03 [CI, -0.04 to -0.01]; low certainty). Evidence on other diets, comparing diets with active comparisons, and on anxiety was limited by study limitations and clinical or methodological heterogeneity. Limited studies did not allow for adequate exploration of heterogeneity. Calorie restrictions and low-fat diets might reduce depressive symptoms among adults with elevated cardiometabolic risk, but the differences were small and confidence in the findings was low. Evidence on other diets, comparisons to active interventions, and other outcomes is limited. None. (PROSPERO: CRD42023485953).
Urbanization and genetic homogenization in the medieval Low Countries revealed through a ten-century paleogenomic study of the city of Sint-Truiden
Authors: Owyn Beneker, Ludovica Molinaro, Meriam Guellil, Stefania Sasso, Helja Kabral, Biancamaria Bonucci, Noah Gaens, Eugenia D'Atanasio, Massimo Mezzavilla, Hélios Delbrassine, Linde Braet, Bart Lambert, Pieterjan Deckers, Simone Andrea Biagini, Ruoyun Hui, Sara Becelaere, Jan Geypen, Maxim Hoebreckx, Birgit Berk, Petra Driesen, April Pijpelink, Philip van Damme, Sofie Vanhoutte, Natasja De Winter, Lehti Saag, Luca Pagani, Kristiina Tambets, Christiana L Scheib, Maarten H D Larmuseau, Toomas Kivisild
Journal: Genome biology (2025)
Enhancing infectious intestinal disease diagnosis through metagenomic and metatranscriptomic sequencing of 1000 human diarrhoeal samples
Authors: Edward Cunningham-Oakes, Blanca M. Perez-Sepulveda, Yan Li, Jay C. D. Hinton, Charlotte A. Nelson, K. Marie McIntyre, Maya Wardeh, Sam Haldenby, Richard Gregory, Miren Iturriza-Gómara, Christiane Hertz-Fowler, Sarah J. O’Brien, Nigel A. Cunliffe, Alistair C. Darby, Frederick J Bolton, Rob M Christley, Helen E Clough, Susan Dawson, Elizabeth Deja, Ann E Durie, Neil Hall, Debbie Howarth, Lirije Hyseni, Kathryn Jackson, Lucy Jones, Trevor Jones, Lois Orton, Jane A Pulman, Alan D Radford, Danielle Reaves, Helen K Ruddock, Darlene A Snape, Debbi Stanistreet, Tamara Thiele, David Williams, Craig Winstanley, Kate Dodd, Peter J Diggle, Alison C Hale, Barry S Rowlingson, Jim Anson, Caroline Corless, Viki Owen, Malcolm Bennett, Lorraine Bolton, John Cheesbrough, Katherine Gray, David Orr, Lorna Wilson, Andrew R Dodgson, Ashley McEwan, Paul Cleary, Alex J Elliot, Ken H Lamden, Lorraine Lighton, Catherine M McCann, Matthieu Pegorie, Nicola Schinaia, Anjila Shah, Gillian E Smith, Roberto Vivancos, Bernard Wood, Rikesh Bhatt, Dyfrig A Hughes, Rob Davie, Simon de Lusigna, Filipa Ferreira, Mariya Hriskova, Sam O’Sullivan, Stacy Shinneman, Ivelina Yonova
Journal: Genome Medicine (2025)
Unravelling the pathogenesis of Oropouche virus
Authors: Anna Clara Gregório Có, Gabriela Colombo de Mendonça, Felipe Donateli Gatti, Thiago de Jesus Sousa, Eric Arrivabene Tavares, Joana Zorzal Nodari, Renan Garcia de Moura, Paola de Oliveira Lopes, Julia Del Piero Pereira, Lyvia Neves Rebello Alves, Tadeu Ériton Caliman Zanardo, Flávio Cunha Monteiro, Claudia N Duarte Dos Santos, Isabela Ribeiro Rodrigues, Jaqueline Pegoretti Goulart, Carlos Henrique Fantecelle, Luciana Polaco Covre, Daniel Claudio Oliveria Gomes, Marco Cesar Cunegundes Guimarães, Andressa Alves Martins Cadete Salles, Dijoce Prates Bezerra, Wanderson de Souza Lugão, Felipe Gomes Naveca, Suwellen Sardinha Dias de Azevedo, Edson Delatorre, Fausto Edmundo Lima Pereira, Rodrigo Ribeiro-Rodrigues
Journal: The Lancet Infectious Diseases (2025)
A new definition of human health is needed to better implement One Health
Authors: Thierry Lefrançois, Jean-Luc Angot, Brigitte Autran, Salome A Bukachi, Elisabeth Claverie de Saint-Martin, Patrick Giraudoux, Estelle Lefrançois, Bruno Lina, Khuat Thi Hai Oanh, David O Obura, Jean-François Delfraissy
Journal: The Lancet (2025)
A simplified approach for diagnosing heart failure with preserved ejection fraction by assessing the left atrium and natriuretic peptides
Authors: Jerremy Weerts, Arantxa Barandiarán Aizpurua, Ravi B. Patel, Arno A. van de Bovenkamp, Hesam Amin, Sandra Sanders‐van Wijk, Sanne G.J. Mourmans, Anouk Achten, M. Louis Handoko, Antoni Bayés‐Genís, Hans‐Peter Brunner‐La Rocca, Sanjiv J. Shah, Christian Knackstedt, Vanessa P.M. van Empel
Journal: European Journal of Heart Failure (2025)

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is common but diagnosing it remains cumbersome and complex. Left atrial (LA) enlargement and dysfunction is an important pathologic marker in HFpEF. We evaluated whether LA measures and circulating natriuretic peptides (NPs) could simplify HFpEF diagnosis as a first step. Methods and results A new, first‐step diagnostic approach to rule in HFpEF is presented using LA volume indexed for height 2 (LAViH2; cut‐off &gt;35.5 ml/m 2 in sinus rhythm, or &gt;38.6 ml/m 2 in atrial fibrillation) and NPs (as per the HFA‐PEFF major criterion). The LA/NP approach was derived from 443 patients with suspected of HFpEF (final diagnosis 84% HFpEF, 16% controls without heart failure), and validated in two independent cohorts (503 patients, 90% HFpEF; and 123 patients undergoing (exercise) right heart catheterization, 86% HFpEF). The LA/NP step identified 60% HFpEF patients with 88% specificity and 97% positive predictive value (PPV) (derivation cohort). Sequentially applying the LA/NP step, and if normal followed by either HFA‐PEFF or H 2 FPEF algorithm, reduced intermediate HFpEF likelihood scores compared to starting with the algorithms, decreasing additional diagnostic needs for HFpEF diagnosis by 27% (HFA‐PEFF) and 56% (H 2 FPEF). Validation cohorts confirmed the LA/NP approach (76–80% specificity, 92–97% PPV, and 21–57% reduction in intermediate scores). Replacing LAViH2 with LA reservoir strain showed comparable results. Conclusion A first‐step approach using enlarged LA volume and elevated NPs simplifies HFpEF diagnosis. This approach identifies most HFpEF patients with high specificity and substantially reduces the need for additional diagnostics by lowering intermediate HFA‐PEFF or H 2 FPEF scores.
Endoscopic ultrasonography-guided hepaticoduodenostomy using a novel self-expandable metallic stent with an ultra-tapered tip and a slim-delivery system
Authors: Haruo Miwa, Yugo Ishino, Kazuki Endo, Ritsuko Oishi, Yuichi Suzuki, Yusuke Suwa, Shin Maeda
Journal: Endoscopy (2025)
Percutaneous cyanoacrylate injection with endoscopic closure using an over-the-scope clip for refractory duodenocutaneous fistula
Authors: Kento Shionoya, Shuntaro Mukai, Atsushi Sofuni, Takayoshi Tsuchiya, Reina Tanaka, Ryosuke Tonozuka, Takao Itoi
Journal: Endoscopy (2025)
Design, synthesis, and antitumor activity of novel thioheterocyclic nucleoside derivatives by suppressing the c-MYC pathway
Authors: Xian-Jia Li, Ke-Xin Huang, Ke-Xin Wang, Ru Liu, Dong-Chao Wang, Yu-Ru Liang, Er-Jun Hao, Yang Wang, Hai-Ming Guo
Journal: Acta Pharmaceutica Sinica B (2025)
Balloon compression technique using an echoendoscopic balloon tip to prevent bile leakage in endoscopic ultrasound-guided choledochoduodenostomy
Authors: Takashi Koriyama, Shunsuke Omoto, Mamoru Takenaka, Michihito Kono, Akito Furuta, Taro Inoue, Wataru Ono
Journal: Endoscopy (2025)
Safety and tolerability of a 5 mg starting dose of vericiguat among patients with heart failure: The <scp>VELOCITY</scp> study
Authors: Stephen J. Greene, Stefano Corda, Ciaran J. McMullan, Giovanni Palombo, Christina Schooss, Vanja Vlajnic, Katrin Walkamp, Michele Senni
Journal: European Journal of Heart Failure (2025)

ABSTRACT Aims In clinical practice, simplifying the number of medication titration steps while maintaining safety may improve the likelihood of patients with heart failure (HF) achieving target doses of guideline‐directed medical therapy (GDMT). The VELOCITY study examined whether removing the 2.5 mg initiation step for vericiguat, and instead initiating therapy at 5 mg daily, would be safe and well‐tolerated. Methods and results VELOCITY was a prospective, 2‐week, single‐arm, open‐label phase 2b study that enrolled patients with chronic HF with ejection fraction &lt;45%, with or without a recent (≤6 or &gt;6 months) worsening HF (WHF) event. Patients with systolic blood pressure &lt;100 mmHg, recent symptomatic hypotension, and recent change in background GDMT or diuretic dosing were excluded. Participants were initiated on vericiguat 5 mg daily and followed for the primary endpoint, defined as completion of 2‐week period with maximum 1‐day interruption and without moderate to severe symptomatic hypotension between Visit 1 (Day 1) and Visit 2 (Day 14). Among 106 study patients (mean age 67 years, 28% female), 50% had recent WHF. Background GDMT included 54% prescribed angiotensin receptor–neprilysin inhibitors and 81% prescribed sodium–glucose cotransporter 2 inhibitors. The primary tolerability endpoint was met in 93.4% of patients, including 90.6% of patients in the WHF group and 96.2% of patients in the non‐WHF group. Tolerability of initiating vericiguat 5 mg was generally consistent across the pre‐specified sensitivity and secondary endpoints. When comparing patients initiating vericiguat 2.5 mg daily in VICTORIA with those starting vericiguat 5 mg daily in VELOCITY, the proportion meeting the VELOCITY primary tolerability endpoint was 97.2% in VICTORIA versus 93.4% in VELOCITY. Conclusions In the prospective VELOCITY study of patients with chronic HF with ejection fraction &lt;45% who were well‐treated with background GDMT, &gt;9 of 10 patients safely tolerated initiation of vericiguat at the 5 mg/day dose. Findings were generally consistent regardless of recent history of WHF. In the context of safety and tolerability data from prior vericiguat studies, VELOCITY supports a potential update in clinical guidance to include a 5 mg starting dose of vericiguat among patients without recent hypotension. Clinical Trials Registration: ClinicalTrials.gov NCT06195930.
Genomic and transcriptomic determinants of clinical outcomes in patients with AML and DNMT3A mutations
Authors: Sao-Chih Ni, Chi-Yuan Yao, Xavier Cheng-Hong Tsai, Min-Yen Lo, Chien-Yuan Chen, Wan-Hsuan Lee, Chien-Chin Lin, Yuan-Yeh Kuo, Yen-Ling Peng, Mei-Hsuan Tseng, Yu-Sin Wu, Ming-Chih Liu, Liang-In Lin, Ming-Kai Chuang, Bor-Sheng Ko, Ming Yao, Jih-Luh Tang, Feng-Ming Tien, Wen-Chien Chou, Hsin-An Hou, Hwei-Fang Tien
Journal: Blood Cancer Journal (2025)

Acute myeloid leukemia (AML) and DNMT3A mutations (DNMT3Amut) are considered to carry intermediate risk under the 2022 European LeukemiaNet (ELN-2022) classification in the absence of other co-mutations or cytogenetic abnormalities. However, this group is highly heterogeneous. In this study, the genomic and transcriptomic features influencing outcomes in DNMT3A-mutated AML were examined in a cohort of 884 patients with AML receiving standard chemotherapy. Stratification by NPM1 and FLT3-ITD status revealed worse survival among patients with NPM1 mutations and wild-type FLT3-ITD (NPM1mut/FLT3-ITDwt) than patients in the ELN-2022 favorable risk group. The other three subgroups (NPM1mut/FLT3-ITDmut, NPM1wt/FLT3-ITDmut, and NPM1wt/FLT3-ITDwt) exhibited worse prognoses than patients in the ELN-2022 intermediate risk group. Additionally, the presence of TET2mut in patients with AML and DNMT3Amut/NPM1mut/FLT3-ITDwt led to reclassification from favorable risk to intermediate risk in the ELN-2022. RNA-sequencing analysis revealed a distinct transcriptomic profile in patients with TET2mut, highlighting the enrichment of leukemic stem cell signatures and dendritic cell migration, with MMP14, CD200, and CT45A5 identified as key differentially expressed genes. In conclusion, co-mutation patterns strongly affected AML outcomes in patients with DNMT3Amut. Patients with TET2mut constituted a unique subgroup within the ELN-2022 favorable DNMT3Amut/NPM1mut/FLT3-ITDwt group, characterized by distinct transcriptomic features and an unfavorable prognosis.