tbuckley/cabot-search huggingface dataset:
Randomized Phase III Study of EGFR Tyrosine Kinase Inhibitor and Intercalated Platinum-doublet Chemotherapy for Non-small Cell Lung Cancer Harboring <i>EGFR</i> Mutation
Authors: Shintaro Kanda, Seiji Niho, Takayasu Kurata, Shogo Nomura, Yosuke Kawashima, Eiji Iwama, Toshihide Yokoyama, Yasutaka Watanabe, Hiroshi Tanaka, Yutaka Fujiwara, Yoshitaka Zenke, Koichi Azuma, Hirokazu Taniguchi, Ryo Toyozawa, Yukio Hosomi, Haruyasu Murakami, Satoshi Hara, Akihiro Bessho, Nobuyuki Yamamoto, Yuichiro Ohe
Journal: Clinical Cancer Research (2025)

Abstract Purpose: This study was performed to confirm the superiority in overall survival (OS) of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) (gefitinib or osimertinib) monotherapy versus EGFR-TKI with intercalation of cisplatin plus pemetrexed as the first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSqNSCLC) harboring EGFR mutation. Patients and Methods: This was an open-label, multicenter, randomized phase III study. Patients with chemotherapy-naïve advanced or recurrent NSqNSCLC harboring EGFR mutation (exon 19 deletion or exon 21 L858R point mutation) were randomly assigned (1:1) to EGFR-TKI monotherapy or EGFR-TKI plus intercalated chemotherapy group. The primary endpoint was OS, and the secondary endpoints included progression-free survival (PFS). Results: From December 2015 to October 2020, 501 patients were randomized. The EGFR-TKI was changed from gefitinib to osimertinib in October 2018 (gefitinib cohort: n=308, osimertinib cohort: n=193). There was no survival advantage in the EGFR-TKI plus intercalated chemotherapy group; the median survival time of both groups was 48.0 months (hazard ratio, 0.985; 91.4% confidence interval, 0.796–1.219; one-sided P=0.4496). The median PFS time was 12.0 months in the EGFR-TKI monotherapy group and 18.0 months in the EGFR-TKI plus intercalated chemotherapy group (hazard ratio, 0.762; 95% confidence interval, 0.628–0.925; one-sided P=0.003). The OS and PFS trends in both gefitinib and osimertinib cohorts were identical to those in the entire population. Conclusions: The intercalation of cisplatin plus pemetrexed after the response to EGFR-TKI improved PFS but not OS compared with EGFR-TKI monotherapy as the first-line treatment for advanced NSqNSCLC harboring EGFR mutation.
The Last Decade in Tricuspid Regurgitation: How Imaging Shaped a Field
Authors: Rebecca T Hahn, Luigi Badano, Fabien Praz, Denisa Muraru, Eustachio Agricola, Nina Ajmone Marsan, Joanna Bartkowiak, Victoria Delgado, Julien Dreyfus, Jörg Hausleiter, Philipp Lurz, Francesco Maisano, Davide Margonato, David Messika-Zeitoun, Maurice Enriquez-Sarano, João L Cavalcante
Journal: JACC. Cardiovascular imaging (2025)
373P: Dissecting the impact of controlling nutritional status (CONUT) score on survival outcomes and immune-inflammatory profiles in patients with advanced NSCLC undergoing chemo-immunotherapy
Authors: G. Mazzaschi, F. Pecci, A. Dodi, P. Tamarozzi, M. Manini, M. Peroni, S. D’Agnelli, M. Pluchino, M. Verzè, R. Minari, F. Perrone, P. Bordi, A. Leonetti, S. Buti, F. Quaini, N. Sverzellati, M. Tiseo
Journal: Journal of Thoracic Oncology (2025)
345TiP: A phase I dose escalation/expansion study of GSK5764227 (GSK’227), a B7-homologue 3 (B7-H3) protein-targeted antibody-drug conjugate (ADC), in combination with standard of care (SoC), in patients with advanced solid tumours, including lung cancers
Authors: H.R. Kim, P. Cassier, G. Daniele, G. Curigliano, J. Hilton, A. Italiano, S. Koganemaru, R.D. Kowalyszyn, P.M. Lorusso, V. Moreno Garcia, M.E. Olmedo Garcia, H.A. Perroud, W.M. Saif, N. Yamamoto, A. Aziez, R. Anjum, J.C. Lamacchia, S.N. Symeonides, J. Huang, V. Subbiah
Journal: Journal of Thoracic Oncology (2025)
347P: AI multimodal tool highlights host and ghost biomarkers for guiding immunotherapy decisions in clinical practice
Authors: V. Miskovic, L. Mazzeo, R. Ferrara, M. Brambilla, C. Silvestri, A. Ferrarin, G. Abolafio, P. Portararo, A. Zanichelli, C.M. Licciardello, L. Provenzano, M. Ganzinelli, T. Beninato, M. Occhipinti, C. Proto, M. Russano, D. Signorelli, G. Lo Russo, S. Sangaletti, A. Prelaj
Journal: Journal of Thoracic Oncology (2025)
323P: Molecular subtypes and their correlation to clinical outcomes in a real-world analysis of patients with extensive stage small cell lung cancer (ES-SCLC) treated with first-line chemoimmunotherapy
Authors: N.M. Zellweger, S. Schmid, I. Alborelli, T. Losmanová, M. Frueh, M. Bertschinger, C. Waibel, F.W.F. Cerciello, P.R. Froesch, M.T. Mark, A. Bettini, P. Häuptle, V. Blum, S. Hayoz, K. Gobat, L.A. Mauti, S.I. Rothschild, S. Savic Prince
Journal: Journal of Thoracic Oncology (2025)
326P: Synergistic interaction between extracellular matrix and epithelial-mesenchymal transition factors drives invasive and metastatic phenotypes in pulmonary neuroendocrine tumors
Authors: T.G. Prieto, C.M. Baldavira, C.S. Faria, A. Ab’Saber, T. Takagaki, V. Capelozzi
Journal: Journal of Thoracic Oncology (2025)
Sex-Specific Association of Left Ventricular Function With Mortality in Severe Mitral Regurgitation
Authors: Soongu Kwak, Byung Joo Sun, Sahmin Lee, Jun-Bean Park, Hyung-Kwan Kim, Yong-Jin Kim, Jong-Min Song, Seung-Pyo Lee, Dae-Hee Kim
Journal: JAMA Network Open (2025)

Importance The association between left ventricular (LV) systolic dysfunction and adverse outcomes in patients with severe degenerative mitral regurgitation (MR) may vary by sex. Objective To investigate the sex-specific association of LV systolic function with mortality in patients with severe degenerative MR. Design, Setting, and Participants This retrospective cohort study included consecutive patients who underwent surgery for severe degenerative MR at 2 tertiary hospitals in South Korea from 2006 to 2020. Preoperative LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) were measured, with absolute LV-GLS values reported. Patients were stratified by LVEF (≤55%, &amp;amp;gt;55% to ≤60%, and &amp;amp;gt;60%) and LV-GLS (&amp;amp;lt;19.9%, ≥19.9% to &amp;amp;lt;23.4%, and ≥23.4%) tertiles. Mortality status was verified through December 2023, with a median (IQR) follow-up duration of 8.2 (5.3-12.2) years. Data analysis was conducted in March 2024. Exposures Surgical MV repair or replacement. Main Outcomes and Measures The primary outcome was all-cause mortality after MV surgery. Restricted cubic spline (RCS) curves visualized the association between LVEF, LV-GLS, and mortality for each sex. Results Among 1686 patients, 1088 (64.5%) were men and 598 (35.5%) were women. Women were older than men (median [IQR] age, 62 [51-70] vs 54 [45-63] years) and had higher LVEF and LV-GLS than men did. During the follow-up, 220 (13.0%) deaths occurred (117 men [10.8%]; 103 women [17.2%]). In Kaplan-Meier curves, mortality in men increased in the lowest LVEF (≤55%) and LV-GLS (&amp;amp;lt;19.9%) groups, whereas women exhibited an earlier increase in mortality at higher LVEF (55%-60%) and LV-GLS (19.9%-23.4%) levels. Multivariable Cox analyses showed a higher mortality risk associated with LVEF less than or equal to 55% (adjusted hazard ratio [HR], 3.48; 95% CI, 1.84-6.58; P &amp;amp;lt; .001) and 55% to 60% (adjusted HR, 2.21; 95% CI, 1.36-3.58; P = .001) compared with LVEF greater than 60% in women, but not in men ( P for interaction by sex = .02). RCS curves showed an earlier increase in mortality risk at higher LVEF and LV-GLS levels in women. Similar trends were observed in asymptomatic patients. Conclusions and Relevance In this cohort study of patients with severe degenerative MR, women had an earlier increase in mortality risk associated with LV systolic dysfunction, suggesting the need to consider sex-specific criteria for early surgery in asymptomatic patients.
Postpartum Hormonal Contraceptive Use and Risk of Depression
Authors: Søren Vinther Larsen, Brice Ozenne, Anders Pretzmann Mikkelsen, Xiaoqin Liu, Kathrine Bang Madsen, Trine Munk-Olsen, Øjvind Lidegaard, Vibe Gedsø Frokjaer
Journal: JAMA Network Open (2025)

Importance Hormonal contraceptive (HC) use is associated with depression. It is, however, unknown whether this is also true in the postpartum period when women have a heightened depression risk and are routinely offered HC treatment. Objective To examine whether HC initiation post partum is associated with the development of depression within 12 months post partum. Design, Setting, and Participants A population-based cohort study based on nationwide Danish register data was conducted including all primiparous women who gave birth from January 1, 1997, through December 31, 2022. Women were excluded if they had depression within 24 months before delivery, multiple births or stillbirth, or a diagnosis of breast cancer or liver tumor. Data analysis was conducted between March 20, 2023, and January 17, 2025. Exposure Hormonal contraceptive initiation within 12 months post partum was treated as a time-varying exposure. Hormonal contraceptive types were categorized as combined oral contraceptives (COCs), combined nonoral contraceptives (CNOCs), progestogen-only pills (POPs), and progestogen-only nonoral contraceptives (PNOCs). Main Outcomes and Measures Depression within 12 months post partum, defined as filling an antidepressant prescription or receiving a hospital diagnosis of depression, was the main outcome. Adjusted hazard ratios (AHRs) and average absolute risks of depression within 12 months post partum were estimated using Cox proportional hazards regression and a G-formula estimator. Results Of 610 038 first-time mothers, 248 274 (40.7%) initiated HCs within 12 months post partum (mean [SD] age, 27.6 [4.3] years for HC users vs 29.6 [4.8] years for nonusers). Hormonal contraceptive initiation was associated with subsequent depression, with an AHR of 1.49 (95% CI, 1.42-1.56) compared with no use, resulting in an increase in the 12-month absolute risk from 1.36% (95% CI, 1.32%-1.39%) to 1.54% (95% CI, 1.50%-1.57%). The AHR for COC was 1.72 (95% CI, 1.63-1.82); CNOC, 1.97 (95% CI, 1.64-2.36); and PNOC, 1.40 (95% CI, 1.25-1.56). Progestogen-only pill exposure was associated with an instantaneously reduced risk in the early study period, but it was increased late post partum. The earlier COCs were initiated post partum the higher the associated rate ratio of depression. Conclusions and Relevance In this cohort study, HC initiation post partum was associated with an instantaneous increased risk of developing depression. The associated risk was higher the earlier it was initiated post partum, at least for COC. This finding raises the issue of whether the incidence of depression post partum is increased by routine HC initiation after childbirth.
<i>N</i>-Acetylcysteine for Hereditary Cystatin C Amyloid Angiopathy
Authors: Asbjorg Osk Snorradottir, Alvaro Gutierrez-Uzquiza, Paloma Bragado, Michael E. March, Charlly Kao, Enrico Bernardo Arkink, Solveig Jonsdottir, Arna Sigurdardottir, Helgi J. Isaksson, Hekla Liv Mariasdóttir, Olga Yr Bjorgvinsdottir, Natalia M. Kowal, Hugrun L. Heimisdottir, Astros Sverrisdottir, Astridur Palsdottir, Hans Tomas Bjornsson, Hakon Hakonarson
Journal: JAMA Neurology (2025)

Importance Hereditary cystatin C amyloid angiopathy (HCCAA) is a lethal, dominantly inherited disease primarily affecting Icelandic young adults that leads to severe cerebral amyloid angiopathy, with no effective therapy. Objective To investigate safety, tolerance, and therapeutic potential of N -acetylcysteine (NAC) in lowering disease-associated biomarkers in sequence variation carriers. Design, Setting, and Participants This phase 2a open-label clinical trial was conducted from March 2019 to December 2021 at a single study center at Landspitali University Hospital in Reykjavik, Iceland, and included 17 confirmed carriers of the L68Q- CST3 sequence variation. Intervention High-dose NAC treatment was administered at 2400 mg daily for 9 months. Participants underwent regular monitoring for hemorrhages and disease progression, including blood and skin biopsy samples obtained every 3 months for biomarker testing. Main Outcomes and Measures The primary outcomes were drug tolerability and safety, cognitive status, and reduction in disease-associated biomarkers in skin biopsies. Secondary outcomes included changes in blood and plasma biomarker levels. Results Of 17 carriers treated, 6 were male and 11 were female, and mean (SD) participant age was 40.0 (4.2) years. Analysis of the primary outcomes showed that NAC was safe and well tolerated. Five cerebral bleeds occurred during the treatment period without permanent neurological sequela; no death occurred. There was significant reduction in median (IQR) disease-specific biomarker levels in skin after treatment, including collagen IV (baseline: 3.69% [2.48%-5.16%]; after treatment: 2.60% [1.99%-2.97%]; P &amp;amp;lt; .001), fibronectin (baseline: 3.17% [2.09%-5.05%]; after treatment: 2.37% [1.87%-3.42%]; P = .01), vimentin (baseline: 1.60% [1.24%-2.37%]; after treatment: 1.31% [0.97%-1.68%]; P &amp;amp;lt; .001), and SMAD (baseline: 2.25% [0.55%-4.36%]; after treatment: 1.56% [0.20%-2.54%]; P &amp;amp;lt; .001) via Wilcoxon matched-pairs signed rank test. Secondary outcomes included a significant increase in reduced glutathione levels and decreased high-molecular-weight cystatin C aggregate levels in plasma after NAC treatment. Conclusions and Relevance In this single-center nonrandomized clinical trial, NAC was safe and well tolerated and decreased disease-associated biomarker and amyloid deposition, suggesting NAC may offer a preventive strategy against HCCAA. Trial Registration ClinicalTrialsRegister.eu Identifier: 2017-004776-56
Generalized Pairwise Comparisons to Support Shared Decision-Making in the CODA Trial
Authors: Samuel Salvaggio, Sarah E. Monsell, Patrick J. Heagerty, Mickael De Backer, Emilie Barré, Jean-Christophe Chiem, Everardo D. Saad, Marc Buyse, David R. Flum
Journal: JAMA Network Open (2025)

Importance Shared decision-making (SDM) can be made difficult by the multifaceted nature of outcome assessment. A rigorous method for analyzing results from multiple outcomes is called generalized pairwise comparisons (GPC), which could assist in SDM. Objective To examine whether GPC can be useful in SDM by using individual-patient data from the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. Design, Setting, and Participants This comparative effectiveness study used data from participants in the multicenter US CODA trial (conducted between May 2016 and March 2020). All possible pairs of patients (one from each arm) were formed to analyze each of 7 outcomes of interest sequentially. Data were analyzed between February 2020 and early 2024. Exposures Three scenarios of priorities related to a different order of outcomes were considered. The first scenario came from a consensus exercise with patients that favored antibiotics, whereas the other 2 were arbitrarily chosen to illustrate the range of possible outcomes depending on prioritizations. Scenario 2 favored neither treatment, and scenario 3 favored appendectomy. Main Outcomes and Measures The primary outcome was the net treatment benefit (NTB), a formal measure of benefit-risk, which is the net probability that a randomly selected patient from the antibiotic-assigned arm would have a more favorable outcome than a randomly selected patient from the appendectomy-assigned arm. Results A total of 1552 patients were included in the CODA trial, with 776 (mean [SD] age, 38.3 [13.4] years; 286 [37%] female) in the antibiotic arm and 776 (mean [SD] age, 37.8 [13.7] years; 290 [37%] female) in the appendectomy arm. The NTB of antibiotic treatment was 12.8% (95% CI, 7.1% to 18.3%; P &amp;amp;lt; .001) for the first scenario, 3.2% (95% CI −2.4% to 8.7%; P = .27) for the second, and −14.5% (95% CI. −20.2% to −8.8%; P &amp;amp;lt; .001) for the third. These results respectively favored antibiotics, neither treatment, or appendectomy, thus illustrating that benefit-risk varies considerably according to individual priorities. Conclusions and Relevance This comparative effectiveness study of antibiotics and appendectomy illustrates that the GPC method is a flexible yet mathematically rigorous quantitative analysis of benefit-risk balance. This method provides a more exhaustive and nuanced quantitative assessment of the differences between 2 treatment modalities in terms of prioritized outcomes. Furthermore, GPC could support SDM by considering individual prioritizations of the multiple outcomes.
Experiences of Obstetrician-Gynecologists Providing Pregnancy Care After <i>Dobbs</i>
Authors: Abigail S. Cutler, Corinne M. Hale, Eliza Bennett, Laura Jacques, Jenny Higgins
Journal: JAMA Network Open (2025)

Importance Following the Dobbs v Jackson Women’s Health Organization ( Dobbs ) decision in June 2022, which overturned the federal right to abortion, Wisconsin physicians faced the threat of an 1849 state law widely interpreted to criminalize provision of abortion except in life-saving emergencies. Physicians and their institutions were left to interpret whether and how they could treat and/or refer certain pregnant patients. Objective To document how the post- Dobbs legal landscape shaped Wisconsin obstetrician-gynecologists’ (OB-GYNs’) ability to provide health care to patients facing pregnancy-related risks and complications, with particular attention to the mediating role of health care institutions. Design, Setting, and Participants In this qualitative study, 21 OB-GYNs were recruited between June 2022 and December 2023 from rural and urban areas with varying hospital affiliations, scopes of practice, and individual demographics to participate in semistructured, remote interviews. Exposure An 1849 abortion law that suspended abortion care in Wisconsin between June 2022 and December 2023. Main Outcomes and Measures Physicians’ perceptions of (1) how the legal landscape shaped management of pregnancy and related complications, and (2) how institutional-level factors contributed to physicians’ experiences caring for pregnant patients following Dobbs . Results This study included 21 OB-GYNs (mean [SD] age, 43 [5.88] years; 16 [76.2%] female; 5 [23.8%] non-White and 16 [76.2%] White) who practiced obstetrics in Wisconsin. OB-GYNs described how the threat of criminalization following Dobbs was detrimental to physicians’ ability to provide pregnancy care. Absence of legal clarity surrounding the 1849 law led to confusion and wide variations in institutional comfort and clinical practice, which resulted in substandard, delayed, and fragmented patient care. Overwhelmingly, the threat of criminalization after Dobbs exacerbated barriers for physicians providing comprehensive pregnancy care and patients seeking it. Conclusions and Relevance In this qualitative study of OB-GYNs practicing in an abortion-restrictive state, threat of criminalization in post- Dobbs Wisconsin resulted in uncertainty and confusion for OB-GYNs and worse care for pregnant patients. The absence of clear guidance and support from institutional and health care system leadership emerged as a particularly salient missed opportunity. These experiences, which contribute to a critical evidence base on the harms of abortion restrictions, are relevant to states facing similar bans that criminalize or restrict health care.
The Role of Clinicians in the Climate Crisis
Authors: Wendy Levinson
Journal: JAMA Network Open (2025)

Hanna Zurl, MD; Zhiyu Qian, MD; Daniel R. Stelzl, MD; Filippo Dagnino, MD; Stephan M. Korn, MD; Muhieddine Labban, MD; Stuart R. Lipsitz, ScD; Marianne Leitsmann, MD, MHBA; Sascha Ahyai, MD; Chad Ellimoottil, MD, MS; Stacy Loeb, MD, MSc; Hari S. Iyer, ScD, MPH; Quoc-Dien Trinh, MD, MBA; Alexander P. Cole, MD
Immortal Time Bias and Nonlinear Stroke Recurrence Risk—Reply
Authors: Lucas V. A. Boersma, David J. Werring, David J. Seiffge
Journal: JAMA Neurology (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Discordance of 10- and 30-Year Predicted Risk for Cardiovascular Disease in US Adults
Authors: Vaishnavi Krishnan, Xiaoning Huang, Amanda M. Perak, Josef Coresh, Chiadi E. Ndumele, Philip Greenland, Donald M. Lloyd-Jones, Sadiya S. Khan
Journal: JAMA (2025)

This study examines the distribution of 10- and 30-year cardiovascular disease risk estimates among US adults.
Potential Benefits of Thiazolidinediones in Combination With Glucagon-Like Peptide-1 Receptor Agonists
Authors: Hermes Florez, Ricardo Correa, Willy Marcos Valencia
Journal: JAMA Network Open (2025)

Jing-Xing Li, MD, MS; Tzu-Ju Hsu, MS; Heng-Jun Lin, MS; Shu-Bai Hsu, BS; Chiung-Ray Lu, MD; Wei-Hsin Chung, MD; Shinn-Jye Liang, MD; Fuu-Jen Tsai, MD, PhD; Kuan-Cheng Chang, MD, PhD
Immortal Time Bias and Nonlinear Stroke Recurrence Risk
Authors: Raed A. Joundi, Shrikant I. Bangdiwala, Mukul Sharma
Journal: JAMA Neurology (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal