tbuckley/cabot-search huggingface dataset:
Apixaban to Prevent Recurrence After Cryptogenic Stroke
Authors: Xin Wen, Jianyun Yan, Zhaohua Zhu
Journal: JAMA (2024)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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 journal
Antithrombotic Treatment for Cervical Artery Dissection
Authors: Josefin E. Kaufmann, Eric L. Harshfield, Henrik Gensicke, Susanne Wegener, Patrik Michel, Georg Kägi, Krassen Nedeltchev, Lars Kellert, Sverre Rosenbaum, Christian H. Nolte, Hanne Christensen, Marcel Arnold, Philippe Lyrer, Christopher Levi, Philip M. Bath, Stefan T. Engelter, Christopher Traenka, Hugh S. Markus, Mohd Nor Azlisham, Rose Boswell, Neil Baldwin, Anthoy Rudd, Isle Burger, Lalit Kalra, Ahamed Hassan, Christopher Price, Anand Dixit, Ronald MacWalter, David Cohen, Richard Davey, Tim Cassidy, Gunarathnam Gunathilagan, Damian Jenkinson, Frances Harrington, Martin James, Graham Venables, Nigel Smyth, Hedley Emsley, Louise Shaw, Joanna Lovett, Paul Guyler, Hugh S Markus, Patrick Gompertz, Debs Kelly, Isam Salih, Brendan Davies, Hamsaraj Shetty, Amit Mistri, David Hargrovers, Khalid Rashed, Brian Clarke, David Collas, Bridget Colam, Rustam Al-Shahi Salman, Richard Gerraty, Jon Sturm, Christopher Levi, Tim Kleinig, Andrew Wrong, Peter Hand, Candice Delcourt, Alice King, Jeremy Madigan, Atkinson Morley, John Norris, Jennifer Peycke, Melina Wilson, Cara Hicks, Elizabeth Hayter, Ranjit Menon, Fiona Kennedy, Usman Khan, Adina Feldman, Matt Hollocks, Graham S Venebales, Sally Kerry, Ahames Hassan, Gary A Ford, Philip M Bath, Chris Weir, Deniy Briley, Ajay Bhalla, Stefan Engelter, Christopher Traenka, Sabine Schaedelin, Philippe Lyrer, M Kloss, D Droste, T Brandt, MN Psychogius, A Brehm, A Grau, P Sandor, S von Felten, A Hammann, Thomas Fabbro, Martina Maurer, Klaus Ehrlich, Astrid Rösler, P Forst, Timo Kahles, Krassen Nedeltchev, Valerian Altersberger, Leo Bonati, Alexander Brehm, N Bruni, Gian-Marco de Marchis, Urs Fisch, Joachim Fladt, Henrik Gensicke, Lisa Hert, Nils Peters, Alexandros Polymeris, C Stippich, Sebastian Thilemann, Benjamin Wagner, Marcel Arnold, Urs Fischer, MR Heldner, David J Seiffge, L Sveikata, R Sztajzel, H Muller, P Correia, A Eskandari, I Meyer, Patrik Michel, S Nannoni, S Remillard, G Sirimarco, A Zachariadis, Georg Kaegi, A Mueller, Jochen Vehoff, J Hamann, Andreas Luft, L Steiner, Susanne Wegener, JH Erdur, Christian Nolte, R v. Rennenberg, JF Scheitz, K Fell, L Kellert, Hanne Christensen, S Rosenbaum
Journal: JAMA Neurology (2024)

Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients.
Is Screening for Primary Aldosteronism Always the Best Option?
Authors: Romain Boulestreau, Thierry Couffinhal
Journal: JAMA Internal Medicine (2024)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 2024 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 Internal Medicine journal
Mortality of Patients With Sepsis Administered Piperacillin-Tazobactam vs Cefepime
Authors: Rishi Chanderraj, Andrew J. Admon, Ying He, Mark Nuppnau, Owen R. Albin, Hallie C. Prescott, Robert P. Dickson, Michael W. Sjoding
Journal: JAMA Internal Medicine (2024)

Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents.
Telehealth Expansion and Medicare Beneficiaries’ Care Quality and Access
Authors: Morteza Saharkhiz, Tanvi Rao, Sara Parker-Lue, Sara Borelli, Karin Johnson, Guido Cataife
Journal: JAMA Network Open (2024)

Importance Understanding the association of telehealth use with health care outcomes is fundamental to determining whether telehealth waivers implemented during the COVID-19 public health emergency should be made permanent. The current literature has yielded inconclusive findings owing to its focus on select states, practices, or health care systems. Objective To estimate the association of telehealth use with outcomes for all Medicare fee-for-service (FFS) beneficiaries by comparing hospital service areas (HSAs) with different levels of telehealth use. Design, Setting, and Participants This US population-based, retrospective cohort study was conducted from July 2022 to April 2023. Participants included Medicare claims of beneficiaries attributed to HSAs with FFS enrollment in Parts A and B. Exposures Low, medium, or high tercile of telehealth use created by ranking HSAs according to the number of telehealth visits per 1000 beneficiaries. Main Outcomes and Measures The primary outcomes were quality (ambulatory care–sensitive [ACS] hospitalizations and emergency department [ED] visits per 1000 FFS beneficiaries), access to care (clinician encounters per FFS beneficiary), and cost (total cost of care for Part A and/or B services per FFS Medicare beneficiary) determined with a difference-in-difference analysis. Results In this cohort study of claims from approximately 30 million Medicare beneficiaries (mean [SD] age in 2019, 71.04 [1.67] years; mean [SD] percentage female in 2019, 53.83% [2.14%]) within 3436 HSAs, between the second half of 2019 and the second half of 2021, mean ACS hospitalizations and ED visits declined sharply, mean clinician encounters per beneficiary declined slightly, and mean total cost of care per beneficiary per semester increased slightly. Compared with the low group, the high group had more ACS hospitalizations (1.63 additional hospitalizations per 1000 beneficiaries; 95% CI, 1.03-2.22 hospitalizations), more clinician encounters (0.30 additional encounters per beneficiary per semester; 95% CI, 0.23-0.38 encounters), and higher total cost of care ($164.99 higher cost per beneficiary per semester; 95% CI, $101.03-$228.96). There was no statistically significant difference in ACS ED visits between the low and high groups. Conclusions and Relevance In this cohort study of Medicare beneficiaries across all 3436 HSAs, high levels of telehealth use were associated with more clinician encounters, more ACS hospitalizations, and higher total health care costs. COVID-19 cases were still high during the period of study, which suggests that these findings partially reflect a higher capacity for providing health services in HSAs with higher telehealth intensity than other HSAs.
The adipose-neural axis is involved in epicardial adipose tissue-related cardiac arrhythmias
Authors: Yubao Fan, Shanshan Huang, Suhua Li, Bingyuan Wu, Qi Zhao, Li Huang, Zhenda Zheng, Xujing Xie, Jia Liu, Weijun Huang, Jiaqi Sun, Xiulong Zhu, Jieming Zhu, Andy Peng Xiang, Weiqiang Li
Journal: Cell Reports Medicine (2024)

Dysfunction of the sympathetic nervous system and increased epicardial adipose tissue (EAT) have been independently associated with the occurrence of cardiac arrhythmia. However, their exact roles in triggering arrhythmia remain elusive. Here, using an in vitro coculture system with sympathetic neurons, cardiomyocytes, and adipocytes, we show that adipocyte-derived leptin activates sympathetic neurons and increases the release of neuropeptide Y (NPY), which in turn triggers arrhythmia in cardiomyocytes by interacting with the Y1 receptor (Y1R) and subsequently enhancing the activity of the Na+/Ca2+ exchanger (NCX) and calcium/calmodulin-dependent protein kinase II (CaMKII). The arrhythmic phenotype can be partially blocked by a leptin neutralizing antibody or an inhibitor of Y1R, NCX, or CaMKII. Moreover, increased EAT thickness and leptin/NPY blood levels are detected in atrial fibrillation patients compared with the control group. Our study provides robust evidence that the adipose-neural axis contributes to arrhythmogenesis and represents a potential target for treating arrhythmia.
Tuft cell-derived acetylcholine promotes epithelial chloride secretion and intestinal helminth clearance
Authors: Tyler E. Billipp, Connie Fung, Lily M. Webeck, Derek B. Sargent, Matthew B. Gologorsky, Zuojia Chen, Margaret M. McDaniel, Darshan N. Kasal, John W. McGinty, Kaitlyn A. Barrow, Lucille M. Rich, Alessio Barilli, Mark Sabat, Jason S. Debley, Chuan Wu, Richard Myers, Michael R. Howitt, Jakob von Moltke
Journal: Immunity (2024)
Clinical and CSF single-cell profiling of post-COVID-19 cognitive impairment
Authors: William T. Hu, Milota Kaluzova, Alice Dawson, Victor Sotelo, Julia Papas, Alexander Lemenze, Carol Shu, Mini Jomartin, Ashima Nayyar, Sabiha Hussain
Journal: Cell Reports Medicine (2024)

Natural history and mechanisms for persistent cognitive symptoms ("brain fog") following acute and often mild COVID-19 are unknown. In a large prospective cohort of people who underwent testing a median of 9 months after acute COVID-19 in the New York City/New Jersey area, we found that cognitive dysfunction is common; is not influenced by mood, fatigue, or sleepiness; and is correlated with MRI changes in very few people. In a subgroup that underwent cerebrospinal fluid analysis, there are no changes related to Alzheimer's disease or neurodegeneration. Single-cell gene expression analysis in the cerebrospinal fluid shows findings consistent with monocyte recruitment, chemokine signaling, cellular stress, and suppressed interferon response—especially in myeloid cells. Longitudinal analysis shows slow recovery accompanied by key alterations in inflammatory genes and increased protein levels of CXCL8, CCL3L1, and sTREM2. These findings suggest that the prognosis for brain fog following COVID-19 correlates with myeloid-related chemokine and interferon-responsive genes.
Advancements in clinical RNA therapeutics: Present developments and prospective outlooks
Authors: Phei Er Saw, Erwei Song
Journal: Cell Reports Medicine (2024)

RNA molecules have emerged as promising clinical therapeutics due to their ability to target "undruggable" proteins or molecules with high precision and minimal side effects. Nevertheless, the primary challenge in RNA therapeutics lies in rapid degradation and clearance from systemic circulation, the inability to traverse cell membranes, and the efficient intracellular delivery of bioactive RNA molecules. In this review, we explore the implications of RNAs in diseases and provide a chronological overview of the development of RNA therapeutics. Additionally, we summarize the technological advances in RNA-screening design, encompassing various RNA databases and design platforms. The paper then presents an update on FDA-approved RNA therapeutics and those currently undergoing clinical trials for various diseases, with a specific emphasis on RNA medicine and RNA vaccines.
Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity
Authors: Marième Ndjim, Imène Gasmi, Fabien Herbert, Charlène Joséphine, Julie Bas, Ali Lamrani, Nathalie Coutry, Sylvain Henry, Valérie S. Zimmermann, Valérie Dardalhon, Marta Campillo Poveda, Evgenia Turtoi, Steeve Thirard, Luc Forichon, Alicia Giordano, Claire Ciancia, Zeinab Homayed, Julie Pannequin, Collette Britton, Eileen Devaney, Tom N. McNeilly, Sylvie Berrard, Andrei Turtoi, Rick M. Maizels, François Gerbe, Philippe Jay
Journal: Immunity (2024)

Upon parasitic helminth infection, activated intestinal tuft cells secrete interleukin-25 (IL-25), which initiates a type 2 immune response during which lamina propria type 2 innate lymphoid cells (ILC2s) produce IL-13. This causes epithelial remodeling, including tuft cell hyperplasia, the function of which is unknown. We identified a cholinergic effector function of tuft cells, which are the only epithelial cells that expressed choline acetyltransferase (ChAT). During parasite infection, mice with epithelial-specific deletion of ChAT had increased worm burden, fitness, and fecal egg counts, even though type 2 immune responses were comparable. Mechanistically, IL-13-amplified tuft cells release acetylcholine (ACh) into the gut lumen. Finally, we demonstrated a direct effect of ACh on worms, which reduced their fecundity via helminth-expressed muscarinic ACh receptors. Thus, tuft cells are sentinels in naive mice, and their amplification upon helminth infection provides an additional type 2 immune response effector function.
Targeting the HSP47-collagen axis inhibits brain metastasis by reversing M2 microglial polarization and restoring anti-tumor immunity
Authors: Li Wang, Cuiying Li, Hongchao Zhan, Shangbiao Li, Kunlin Zeng, Chang Xu, Yulong Zou, Yuxin Xie, Ziling Zhan, Shengqi Yin, Yu Zeng, Xiaoxia Chen, Guangzhao Lv, Zelong Han, Dexiang Zhou, Dong Zhou, Yong Yang, Aidong Zhou
Journal: Cell Reports Medicine (2024)

Brain metastases (BrMs) are the leading cause of death in patients with solid cancers. BrMs exhibit a highly immunosuppressive milieu and poor response to immunotherapies; however, the underlying mechanism remains largely unclear. Here, we show that upregulation of HSP47 in tumor cells drives metastatic colonization and outgrowth in the brain by creating an immunosuppressive microenvironment. HSP47-mediated collagen deposition in the metastatic niche promotes microglial polarization to the M2 phenotype via the α2β1 integrin/nuclear factor κB pathway, which upregulates the anti-inflammatory cytokines and represses CD8
Prognostic Value of Cardiovascular Biomarkers in the Population
Authors: Johannes Tobias Neumann, Raphael Twerenbold, Jessica Weimann, Christie M. Ballantyne, Emelia J. Benjamin, Simona Costanzo, James A. de Lemos, Christopher R. deFilippi, Augusto Di Castelnuovo, Chiara Donfrancesco, Marcus Dörr, Kai M. Eggers, Gunnar Engström, Stephan B. Felix, Marco M. Ferrario, Ron T. Gansevoort, Simona Giampaoli, Vilmantas Giedraitis, Pär Hedberg, Licia Iacoviello, Torben Jørgensen, Frank Kee, Wolfgang Koenig, Kari Kuulasmaa, Joshua R. Lewis, Thiess Lorenz, Magnus N. Lyngbakken, Christina Magnussen, Olle Melander, Matthias Nauck, Teemu J. Niiranen, Peter M. Nilsson, Michael H. Olsen, Torbjorn Omland, Viktor Oskarsson, Luigi Palmieri, Anette Peters, Richard L. Prince, Vazhma Qaderi, Ramachandran S. Vasan, Veikko Salomaa, Susana Sans, J. Gustav Smith, Stefan Söderberg, Barbara Thorand, Andrew M. Tonkin, Hugh Tunstall-Pedoe, Giovanni Veronesi, Tetsu Watanabe, Masafumi Watanabe, Andreas M. Zeiher, Tanja Zeller, Stefan Blankenberg, Francisco Ojeda
Journal: JAMA (2024)

Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.
Apixaban to Prevent Recurrence After Cryptogenic Stroke
Authors: Kuan-Yu Chi, Michele Nanna, Michael G. Nanna
Journal: JAMA (2024)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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 journal
Effect of Low-Dose Iron Supplementation on Early Development in Breastfed Infants
Authors: Ludwig Svensson, Grzegorz Chmielewski, Emilia Czyżewska, Magnus Domellöf, Zofia Konarska, Małgorzata Pieścik-Lech, Cornelia Späth, Hania Szajewska, Anna Chmielewska
Journal: JAMA Pediatrics (2024)

Importance Breastfed infants are at risk of iron deficiency, which is associated with suboptimal development. There is a paucity of evidence on the effects of iron supplementation on child development, and current guidelines are divergent. Objective To assess whether daily iron supplementation, 1 mg/kg, between 4 and 9 months in exclusively or predominantly breastfed infants improves psychomotor development at 12 months. Design, Setting, and Participants This was a randomized, double-blind, placebo-controlled trial conducted between December 2015 and May 2020 with follow-up through May 2023 in an outpatient setting in Poland and Sweden. Participants were healthy singleton infants born at term with birth weight greater than 2500 g who were exclusively or predominantly breastfed (&amp;amp;gt;50%) and did not have anemia (hemoglobin &amp;amp;gt;10.5 g/dL) at age 4 months. Exclusion criteria included major illness, congenital anomaly, food allergy, and difficulty communicating with caregivers. Interventions Iron (micronized microencapsulated ferric pyrophosphate), 1 mg/kg, or placebo (maltodextrin) once daily from age 4 to 9 months. Main Outcomes and Measures The primary outcome was psychomotor development assessed by motor score of Bayley Scales of Infant and Toddler Development III at 12 months, adjusted for gestational age, sex, and maternal education. Secondary outcomes included cognitive and language scores at 12 months; motor, cognitive, and language scores at 24 and 36 months; iron deficiency (serum ferritin &amp;amp;lt;12 ng/mL), and iron deficiency anemia (iron deficiency and hemoglobin &amp;amp;lt;10.5 g/dL) at 12 months. Results Of 221 randomized infants (111 female), 200 (90%) were included in the intention-to-treat analysis (mean [SD] age, 12.4 [0.8] months). Iron supplementation (n = 104) compared to placebo (n = 96) had no effect on psychomotor development (mean difference [MD] for motor score, −1.07 points; 95% CI, −4.69 to 2.55), cognitive score (MD, −1.14; 95% CI, −4.26 to 1.99), or language score (MD, 0.75; 95% CI, −2.31 to 3.82) at 12 months. There were no significant differences at 24 and 36 months. The intervention did not reduce the risk for iron deficiency (relative risk [RR], 0.46; 95% CI, 0.16 to 1.30) or iron deficiency anemia (RR, 0.78; 95% CI, 0.05 to 12.46) at 12 months. Conclusion and Relevance No benefit was found with daily low-dose iron supplementation between 4 and 9 months with respect to psychomotor development, risk of iron deficiency, or iron deficiency anemia among breastfed infants in a setting of low risk of anemia. Trial Registration ClinicalTrials.gov Identifier: NCT02242188
A Proof-of-Concept Study of Sequential Treatment with the HDAC Inhibitor Vorinostat following BRAF and MEK Inhibitors in <i>BRAF</i> <i>V600</i>-Mutated Melanoma
Authors: Alaa Embaby, Sanne C.F.A. Huijberts, Liqin Wang, Rodrigo Leite de Oliveira, Hilde Rosing, Bastiaan Nuijen, Joyce Sanders, Ingrid Hofland, Charlaine van Steenis, Roelof J.C. Kluin, Cor Lieftink, Christopher G. Smith, Christian U. Blank, Johannes V. van Thienen, John B.A.G. Haanen, Neeltje Steeghs, Frans L. Opdam, Jos H. Beijnen, Alwin D.R. Huitema, Rene Bernards, Jan H.M. Schellens, Sofie Wilgenhof
Journal: Clinical Cancer Research (2024)

Abstract Purpose: The development of resistance limits the clinical benefit of BRAF and MEK inhibitors (BRAFi/MEKi) in BRAFV600-mutated melanoma. It has been shown that short-term treatment (14 days) with vorinostat was able to initiate apoptosis of resistant tumor cells. We aimed to assess the antitumor activity of sequential treatment with vorinostat following BRAFi/MEKi in patients with BRAFV600-mutated melanoma who progressed after initial response to BRAFi/MEKi. Patients and Methods: Patients with BRAFi/MEKi-resistant BRAFV600-mutated melanoma were treated with vorinostat 360 mg once daily for 14 days followed by BRAFi/MEKi. The primary endpoint was an objective response rate of progressive lesions of at least 30% according to Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included progression-free survival, overall survival, safety, pharmacokinetics of vorinostat, and translational molecular analyses using ctDNA and tumor biopsies. Results: Of the 26 patients with progressive BRAFi/MEKi-resistant BRAFV600-mutated melanoma receiving treatment with vorinostat, 22 patients were evaluable for response. The objective response rate was 9%, with one complete response for 31.2 months and one partial response for 14.9 months. Median progression-free survival and overall survival were 1.4 and 5.4 months, respectively. Common adverse events were fatigue (23%) and nausea (19%). ctDNA analysis showed emerging secondary mutations in NRAS and MEK in eight patients at the time of BRAFi/MEKi resistance. Elimination of these mutations by vorinostat treatment was observed in three patients. Conclusions: Intermittent treatment with vorinostat in patients with BRAFi/MEKi-resistant BRAFV600-mutated melanoma is well tolerated. Although the primary endpoint of this study was not met, durable antitumor responses were observed in a minority of patients (9%).