tbuckley/cabot-search huggingface dataset:
Cancer Stage Compared With Mortality as End Points in Randomized Clinical Trials of Cancer Screening
Authors: Xiaoshuang Feng, Hana Zahed, Justina Onwuka, Matthew E. J. Callister, Mattias Johansson, Ruth Etzioni, Hilary A. Robbins
Journal: JAMA (2024)

Importance Randomized clinical trials of cancer screening typically use cancer-specific mortality as the primary end point. The incidence of stage III-IV cancer is a potential alternative end point that may accelerate completion of randomized clinical trials of cancer screening. Objective To compare cancer-specific mortality with stage III-IV cancer as end points in randomized clinical trials of cancer screening. Design, Setting, and Participants This meta-analysis included 41 randomized clinical trials of cancer screening conducted in Europe, North America, and Asia published through February 19, 2024. Data extracted included numbers of participants, cancer diagnoses, and cancer deaths in the intervention and comparison groups. For each clinical trial, the effect of screening was calculated as the percentage reduction between the intervention and comparison groups in the incidence of participants with cancer-specific mortality and stage III-IV cancer. Exposures Randomization to a cancer screening test or to a comparison group in a clinical trial of cancer screening. Main Outcomes and Measures End points of cancer-specific mortality and incidence of stage III-IV cancer were compared using Pearson correlation coefficients with 95% CIs, linear regression, and fixed-effects meta-analysis. Results The included randomized clinical trials tested benefits of screening for breast (n = 6), colorectal (n = 11), lung (n = 12), ovarian (n = 4), prostate (n = 4), and other cancers (n = 4). Correlation between reductions in cancer-specific mortality and stage III-IV cancer varied by cancer type ( I 2 = 65%; P = .02). Correlation was highest for trials that screened for ovarian (Pearson ρ = 0.99 [95% CI, 0.51-1.00]) and lung (Pearson ρ = 0.92 [95% CI, 0.72-0.98]) cancers, moderate for breast cancer (Pearson ρ = 0.70 [95% CI, −0.26 to 0.96]), and weak for colorectal (Pearson ρ = 0.39 [95% CI, −0.27 to 0.80]) and prostate (Pearson ρ = −0.69 [95% CI, −0.99 to 0.81]) cancers. Slopes from linear regression were estimated as 1.15 for ovarian cancer, 0.75 for lung cancer, 0.40 for colorectal cancer, 0.28 for breast cancer, and −3.58 for prostate cancer, suggesting that a given magnitude of reduction in incidence of stage III-IV cancer produced different magnitudes of change in incidence of cancer-specific mortality ( P for heterogeneity = .004). Conclusions and Relevance In randomized clinical trials of cancer screening, incidence of late-stage cancer may be a suitable alternative end point to cancer-specific mortality for some cancer types, but is not suitable for others. These results have implications for clinical trials of multicancer screening tests.
Late-Stage Cancer End Points to Speed Cancer Screening Clinical Trials—Not So Fast
Authors: Peter B. Bach
Journal: JAMA (2024)

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Prevalence of Cardiovascular Disease and Risk Factors Among Former National Football League Players
Authors: Alexis K. Okoh, Michael K.D. Amponsah, Shannon Cheffet-Walsh, Mehul Patel, David Carfagno, Druenell Linton, Robert Dimeff, David Braunreiter, Phillips Harrington, Fred H. Brennan, Clifford Kavinsky, Marlon Everett, Brandon Park, Marissa Gunnarsson, Sean Snowden, Lidia Mootz, Tenley Koepnick, Jaime Wheeler, Sarah E. Clarke, Heather Prince, Anna Sannino, Paul Grayburn, E. Lee Rice
Journal: Journal of the American College of Cardiology (2024)

Cardiovascular disease (CVD) is the leading cause of death worldwide, but prevalence estimates in former professional athletes are limited. The HUDDLE trial aimed to raise awareness and estimate the prevalence of CVD and associated risk factors among members of the National Football League (NFL) Alumni Association and their families through education and screening events. HUDDLE was a multi-city, cross-sectional study of NFL alumni and family members aged 50 years and above. Subjects reported their health history and participated in CVD education and screening (blood pressure [BP], electrocardiogram [EKG], and transthoracic echocardiogram [TTE] assessments). Phone follow-up by investigators occurred 30-days post-screening to review results and recommendations. This analysis focuses on former NFL athletes. Of 498 participants screened, 57.2% (N=285) were former NFL players, majority of which were African American (67.6%). The prevalence of hypertension among NFL alumni was estimated to be 89.8%, though only 37.5% reported a history of hypertension. Of 285 evaluable participants 61.8% had structural cardiac abnormalities by TTE. Multivariable analysis showed that HTN was a significant predictor of clinically-relevant structural abnormalities on TTE. The HUDDLE trial identified a large discrepancy between participant self-awareness and actual prevalence of CVD and risk factors, highlighting a significant opportunity for population health interventions. Structural cardiac abnormalities were observed in most participants and were independently predicted by HTN, affirming the role of TTE for CVD screening in this over 50 population.
CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma
Authors: Sumanta K. Pal, Ben Tran, John B.A.G. Haanen, Michael E. Hurwitz, Adrian Sacher, Nizar M. Tannir, Lihua E. Budde, Simon J. Harrison, Sebastian Klobuch, Sagar S. Patel, Luis Meza, Mary-Lee Dequeant, Anna Ma, Qiuling Ally He, Leah M. Williams, Alissa Keegan, Ellen B. Gurary, Henia Dar, Sushant Karnik, Changan Guo, Heidi Heath, Rachel R. Yuen, Phuong K. Morrow, Neeraj Agarwal, Samer A. Srour
Journal: Cancer Discovery (2024)

Abstract Therapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors. We also report results from 16 patients with relapsed/refractory ccRCC who received CTX130 in a phase I, multicenter, first-in-human clinical trial. No patients encountered dose-limiting toxicity, and disease control was achieved in 81.3% of patients. One patient remains in a durable complete response at 3 years. Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. These data represent a proof of concept for the treatment of ccRCC and other CD70+ malignancies with CD70− targeted allogeneic CAR T cells. Significance: Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors. See corresponding author Sumanta K. Pal discuss this research article, published simultaneously at the AACR Annual Meeting 2024: https://vimeo.com/932606570/887520f9cb
An “Inclisiran First” Strategy vs Usual Care in Patients With Atherosclerotic Cardiovascular Disease
Authors: Michael J. Koren, Fatima Rodriguez, Cara East, Peter P. Toth, Veena Watwe, Cheryl A. Abbas, Samiha Sarwat, Kelly Kleeman, Biswajit Kumar, Yousuf Ali, Naseem Jaffrani
Journal: Journal of the American College of Cardiology (2024)

Most patients with atherosclerotic cardiovascular disease (ASCVD) fail to achieve guideline-directed low-density lipoprotein cholesterol (LDL-C) goals. Twice-yearly inclisiran lowers LDL-C by ∼50% when added to statins. To evaluate the effectiveness of an "inclisiran first" implementation strategy (adding inclisiran immediately upon failure to reach LDL-C <70 mg/dL despite receiving maximally tolerated statins) versus representative usual care in US patients with ASCVD. VICTORION-INITIATE, a prospective, pragmatically designed trial, randomized patients 1:1 to inclisiran (284 mg at Days 0, 90, and 270) plus usual care (lipid management at treating physician's discretion) versus usual care alone. Primary endpoints were percentage change in LDL-C from baseline and statin discontinuation rates. We randomized 450 patients (30.9% female, 12.4% Black, 15.3% Hispanic); mean baseline LDL-C 97.4 mg/dL. The "inclisiran first" strategy led to significantly greater reductions in LDL-C from baseline to Day 330 versus usual care (60.0% vs 7.0%; p<0.001). Statin discontinuation rates with "inclisiran first" (6.0%) were noninferior versus usual care (16.7%). More "inclisiran first" patients achieved LDL-C goals vs usual care (<70 mg/dL: 81.8% vs 22.2%; <55 mg/dL: 71.6% vs 8.9%; p<0.001). Treatment-emergent adverse event (TEAE) and serious TEAE rates compared similarly between treatment strategies (62.8% vs 53.7% and 11.5% vs 13.4%, respectively). Injection-site TEAEs and TEAEs causing treatment withdrawal occurred more commonly with "inclisiran first" than usual care (10.3% vs 0.0%, and 2.6% vs 0.5%, respectively). An "inclisiran first" implementation strategy led to greater LDL-C lowering compared with usual care without discouraging statin use or raising new safety concerns.
Artificial Intelligence in Cardiovascular Care—Part 2: Applications
Authors: Sneha S. Jain, Pierre Elias, Timothy Poterucha, Michael Randazzo, Francisco Lopez Jimenez, Rohan Khera, Marco Perez, David Ouyang, James Pirruccello, Michael Salerno, Andrew J. Einstein, Robert Avram, Geoffrey H. Tison, Girish Nadkarni, Vivek Natarajan, Emma Pierson, Ashley Beecy, Deepa Kumaraiah, Chris Haggerty, Jennifer N. Avari Silva, Thomas M. Maddox
Journal: Journal of the American College of Cardiology (2024)
Artificial Intelligence for Cardiovascular Care—Part 1: Advances
Authors: Pierre Elias, Sneha S. Jain, Timothy Poterucha, Michael Randazzo, Francisco Lopez Jimenez, Rohan Khera, Marco Perez, David Ouyang, James Pirruccello, Michael Salerno, Andrew J. Einstein, Robert Avram, Geoffrey H. Tison, Girish Nadkarni, Vivek Natarajan, Emma Pierson, Ashley Beecy, Deepa Kumaraiah, Chris Haggerty, Jennifer N. Avari Silva, Thomas M. Maddox
Journal: Journal of the American College of Cardiology (2024)
Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials
Authors: Javed Butler, Sanjiv J Shah, Mark C Petrie, Barry A Borlaug, Steen Z Abildstrøm, Melanie J Davies, G Kees Hovingh, Dalane W Kitzman, Daniél Vega Møller, Subodh Verma, Mette Nygaard Einfeldt, Marie L Lindegaard, Søren Rasmussen, Walter Abhayaratna, Fozia Z Ahmed, Tuvia Ben-Gal, Vijay Chopra, Justin A Ezekowitz, Michael Fu, Hiroshi Ito, Małgorzata Lelonek, Vojtěch Melenovský, Bela Merkely, Julio Núñez, Eduardo Perna, Morten Schou, Michele Senni, Kavita Sharma, Peter van der Meer, Dirk Von Lewinski, Dennis Wolf, Mikhail N Kosiborod
Journal: The Lancet (2024)
Contemporary Decongestion Strategies in Patients Hospitalized for Heart Failure
Authors: Jimmy Zheng, Andrew P. Ambrosy, Ankeet S. Bhatt, Sean P. Collins, Kelsey M. Flint, Gregg C. Fonarow, Marat Fudim, Stephen J. Greene, Anuradha Lala, Jeffrey M. Testani, Anubodh S. Varshney, Ryan S.K. Wi, Alexander T. Sandhu
Journal: JACC Heart Failure (2024)
The rising roles of exosomes in the tumor microenvironment reprogramming and cancer immunotherapy
Authors: Yu Wu, Wenyan Han, Hairong Dong, Xiaofeng Liu, Xiulan Su
Journal: MedComm (2024)

Abstract Exosomes are indispensable for intercellular communications. Tumor microenvironment (TME) is the living environment of tumor cells, which is composed of various components, including immune cells. Based on TME, immunotherapy has been recently developed for eradicating cancer cells by reactivating antitumor effect of immune cells. The communications between tumor cells and TME are crucial for tumor development, metastasis, and drug resistance. Exosomes play an important role in mediating these communications and regulating the reprogramming of TME, which affects the sensitivity of immunotherapy. Therefore, it is imperative to investigate the role of exosomes in TME reprogramming and the impact of exosomes on immunotherapy. Here, we review the communication role of exosomes in regulating TME remodeling and the efficacy of immunotherapy, as well as summarize the underlying mechanisms. Furthermore, we also introduce the potential application of the artificially modified exosomes as the delivery systems of antitumor drugs. Further efforts in this field will provide new insights on the roles of exosomes in intercellular communications of TME and cancer progression, thus helping us to uncover effective strategies for cancer treatment.
Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial
Authors: Zhen Ge, Jing Kan, Xiaofei Gao, Afsar Raza, Jun-Jie Zhang, Bilal S Mohydin, Fentang Gao, Yibing Shao, Yan Wang, Hesong Zeng, Feng Li, Hamid Sharif Khan, Naeem Mengal, Hongliang Cong, Mingliang Wang, Lianglong Chen, Yongyue Wei, Feng Chen, Gregg W Stone, Shao-Liang Chen, Xiaobo Li, Zhen Ge, Jing Kan, Muhammed Anjum, Fei Ye, Xiaofei Gao, Anjum Jalal, Ping Xie, Ling Tao, Xiang Chen, Hamid S Khan, Asim Javed, Yibin Shao, Xiaomei Guo, Feng Li, Tahir Saghir, Naeem Mengal, Shaoping Nie, Hong Qu, Xuesong Qian, Song Yang, Jing Chen, Dasheng Gao, Lijun Liu, Mingliang Wang, Lianglong Chen, Fan Liu, Tan Xu, Yinwu Liu, Badar Ul Ahad Gill, Qing Yang, Nin Guo, Shangyu Wen, Hongliang Cong, Lang Hong, Imad Sheiban, Afsar Raza, Yongyue Wei, Feng Chen, Gary S Mintz, Jun-Jie Zhang, Gregg W Stone, Shao-Liang Chen
Journal: The Lancet (2024)
Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis
Authors: Jiangyi Liu, Xingyun Liao, Na Li, Zongren Xu, Wang Yang, Hongxiu Zhou, Yusen Liu, Zhi Zhang, Guoqing Wang, Shengping Hou
Journal: MedComm (2024)

Abstract Autoimmune uveitis (AU) is a kind of immune‐mediated disease resulting in irreversible ocular damage and even permanent vision loss. However, the precise mechanism underlying dynamic immune changes contributing to disease initiation and progression of AU remains unclear. Here, we induced an experimental AU (EAU) model with IRBP 651‐670 and found that day[D]14 was the inflammatory summit with remarking clinical and histopathological manifestations and the activation of retinal microglia exhibited a time‐dependent pattern in the EAU course. We conducted single‐cell RNA sequencing of retinal immune cells in EAU mice at four time points and found microglia constituting the largest proportion, especially on D14. A novel inflammatory subtype ( Cd74 high Ccl5 high ) of retinal microglia was identified at the disease peak that was closely associated with modulating immune responses. In vitro experiments indicated that inflammatory stimuli induced proinflammatory microglia with the upregulation of CD74 and CCL5, and CD74 overexpression in microglia elicited their proinflammatory phenotype via nuclear factor‐kappa B signaling that could be attenuated by the treatment of neutralizing CCL5 antibody to a certain extent. In‐vivo blockade of Cd74 and Ccl5 effectively alleviated retinal microglial activation and disease phenotype of EAU. Therefore, we propose targeting CD74 and CCL5 of retinal microglia as promising strategies for AU treatment.
Interplay of IL‐17A/IL‐17RA signaling with microbial homeostasis in systemic anti‐tumoral responses
Authors: Shi‐jun He, Jian‐ping Zuo, Ze‐min Lin
Journal: MedComm (2024)

Enteric IL-17RA deficiency leads to gut dysbiosis, consequently initiating the proliferation of tumors at remote locations. The deficiency or blockade of enteric IL-17RA induces the secretion of IL-17A by B cells and Th17 cells in response to microbial signals, resulting in a systemic elevation of IL-17A and fostering the growth of remote tumors. This figure was created with BioRender.com.
miR‐1246 promotes osteosarcoma cell migration via NamiRNA‐enhancer network dependent on Argonaute 2
Authors: Shuai Yang, Qingping Zou, Ying Liang, Dapeng Zhang, Lina Peng, Wei Li, Wenxuan Li, Mengxing Liu, Ying Tong, Lu Chen, Peng Xu, Zhicong Yang, Kaicheng Zhou, Jianru Xiao, Hailin Wang, Wenqiang Yu
Journal: MedComm (2024)

Abstract High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR‐1246 levels. Specially, miR‐1246 located in nucleus could activate the migration gene expression (such as MMP1 ) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR‐1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR‐1246 in vivo. Collectively, our findings suggest that miR‐1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA‐targeted gene activation and the potential of miR‐1246 for osteosarcoma metastasis therapy.
Sodium-Glucose Cotransporter-2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis
Authors: Siddharth M. Patel, Yu Mi Kang, KyungAh Im, Brendon L. Neuen, Stefan D. Anker, Deepak L. Bhatt, Javed Butler, David Z.I. Cherney, Brian L. Claggett, Robert A. Fletcher, William G. Herrington, Silvio E. Inzucchi, Meg J. Jardine, Kenneth W. Mahaffey, Darren K. McGuire, John J.V. McMurray, Bruce Neal, Milton Packer, Vlado Perkovic, Scott D. Solomon, Natalie Staplin, Muthiah Vaduganathan, Christoph Wanner, David C. Wheeler, Faiez Zannad, Yujie Zhao, Hiddo J.L. Heerspink, Marc S. Sabatine, Stephen D. Wiviott
Journal: Circulation (2024)

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular events (MACE) across different patient populations are less clear.
Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction
Authors: Troels Yndigegn, Bertil Lindahl, Katarina Mars, Joakim Alfredsson, Jocelyne Benatar, Lisa Brandin, David Erlinge, Ola Hallen, Claes Held, Patrik Hjalmarsson, Pelle Johansson, Patric Karlström, Thomas Kellerth, Toomas Marandi, Annica Ravn-Fischer, Johan Sundström, Ollie Östlund, Robin Hofmann, Tomas Jernberg
Journal: New England Journal of Medicine (2024)

Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists.
Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock
Authors: Jacob E Møller, Thomas Engstrøm, Lisette O Jensen, Hans Eiskjær, Norman Mangner, Amin Polzin, P Christian Schulze, Carsten Skurk, Peter Nordbeck, Peter Clemmensen, Vasileios Panoulas, Sebastian Zimmer, Andreas Schäfer, Nikos Werner, Martin Frydland, Lene Holmvang, Jesper Kjærgaard, Rikke Sørensen, Jacob Lønborg, Matias G Lindholm, Nanna L J Udesen, Anders Junker, Henrik Schmidt, Christian J Terkelsen, Steffen Christensen, Evald H Christiansen, Axel Linke, Felix J Woitek, Ralf Westenfeld, Sven Möbius-Winkler, Kristian Wachtell, Hanne B Ravn, Jens F Lassen, Søren Boesgaard, Oke Gerke, Christian Hassager
Journal: New England Journal of Medicine (2024)

The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear.
Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus
Authors: Howard C Herrmann, Roxana Mehran, Daniel J Blackman, Stephen Bailey, Helge Möllmann, Mohamed Abdel-Wahab, Walid Ben Ali, Paul D Mahoney, Hendrik Ruge, David A Wood, Sabine Bleiziffer, Basel Ramlawi, Hemal Gada, Anna Sonia Petronio, Charles D Resor, William Merhi, Bruno Garcia Del Blanco, Guilherme F Attizzani, Wayne B Batchelor, Linda D Gillam, Mayra Guerrero, Toby Rogers, Joshua D Rovin, Molly Szerlip, Brian Whisenant, G Michael Deeb, Kendra J Grubb, Ratnasari Padang, Myra T Fan, Andrew D Althouse, Didier Tchétché
Journal: New England Journal of Medicine (2024)

Patients with severe aortic stenosis and a small aortic annulus are at risk for impaired valvular hemodynamic performance and associated adverse cardiovascular clinical outcomes after transcatheter aortic-valve replacement (TAVR).
Routine Beta-Blockers in Secondary Prevention — On Injured Reserve
Authors: P Gabriel Steg
Journal: New England Journal of Medicine (2024)

The benefit of beta-blockers after myocardial infarction was established before the advent of reperfusion and percutaneous coronary intervention and the availability of effective secondary preventive medications.1-3 Since these other treatments became accessible, the value of beta-blocker therapy in patients with coronary artery disease or myocardial infarction but without heart failure has been challenged. Observational studies have yielded conflicting results,4-6 and so far, only one small, open-label, randomized trial has been conducted, which showed no difference in clinical outcomes after 3 years.7 Yndigegn et al.8 now present in the Journal the results of the REDUCE-AMI trial (Randomized Evaluation of Decreased Usage . . .