tbuckley/cabot-search huggingface dataset:
Ramucirumab (RAM) as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline α-fetoprotein (AFP): An analysis of AFP kinetics in the phase III REACH-2 study.
Authors: Richard S. Finn, Masatoshi Kudo, Yoon-Koo Kang, Chia-Jui Yen, Peter R. Galle, Josep Llovet, Eric Assenat, Giovanni Brandi, Ho Yeong Lim, Marc Pracht, Kun Ming Rau, Philippe Merle, Kenta Motomura, Izumi Ohno, Bruno Daniele, Dongbok Shin, Guido Gerken, Paolo Abada, Yanzhi Hsu, Andrew X. Zhu
Journal: Journal of Clinical Oncology (2019)

326 Background: REACH-2 (NCT02435433) demonstrated a significant survival benefit with RAM vs placebo in the second-line treatment of patients with advanced HCC and AFP ≥ 400 ng/mL. This analysis investigated changes in AFP during treatment, as well as potential relationships with survival or progression. Methods: Patients were randomized (2:1) to RAM 8 mg/kg IV or placebo Q2W plus best supportive care until disease progression or unacceptable toxicity. Serum AFP levels were measured at baseline and every 3 cycles. Percent change in AFP from baseline was analyzed at each time point up to Cycle 12 with descriptive statistics and Wilcoxon rank sum test between treatment arms. AFP response was defined as ≥ 20% decrease from baseline. The association between AFP progression and radiographic progression in each time interval was assessed by odds ratio [OR] and Fisher’s exact test. Time to AFP progression and time to radiographic progression (TTP) were evaluated by the Kaplan-Meier method and compared between treatment arms using a stratified log-rank test. AFP progression was defined as ≥ 20% increase from baseline. Hazard ratio (HR) was generated using a stratified Cox regression model. Results: AFP response was significantly higher with RAM compared with placebo (42.1% vs 10.5%, p &lt; 0.0001). Overall survival (OS) was longer in patients with AFP response (13.5 months) than in patients without (6.7 months), irrespective of treatment (HR 0.470, p &lt; 0.0001). The median percent increase in AFP level from baseline was smaller in the patient population treated with RAM (0.4%, 6.1%, 15.4%, 10.8%) than with placebo (45.7%, 98.5%, 122.2%, 91.3%) at Cycles 3, 6, 9 and 12, respectively. Time to AFP progression (HR 0.422, p &lt; 0.0001) and TTP (HR 0.427, p &lt; 0.0001) favored a RAM benefit; subsequent analyses demonstrated a strong association between AFP progression and radiographic progression at 6 weeks (OR 2.44, p &lt; 0.0084) and at 12 weeks (OR 1.89, p = 0.0430). Conclusions: Changes in AFP levels were associated with TTP and OS. RAM prolonged time to AFP progression and radiographic TTP, and slowed the rate of AFP increase during treatment. Clinical trial information: NCT02435433.
Abstract 17265: Coronary CT Angiography and Stress Testing Do Not Improve Clinical Outcomes in Low- to Intermediate-Risk Patients Presenting to the Emergency Department With Acute Chest Pain
Authors: Samuel Reinhardt, Chien-Jung Lin, Eric Novak, David L Brown
Journal: Circulation (2017)

Introduction: Approximately 6 million patients in the US present to emergency departments (ED) each year with chest pain suggestive of an acute coronary syndrome (ACS). The evaluation of such patie...
Abstract 18438: Hypercoagulability in Anticoagulation-Naive Young Paroxysmal Atrial Fibrillation Patients
Authors: Anne H Hobbelt, Michiel Rienstra, Harry J Crijns, Elton A Dudink, Hugo Ten Cate, Rene Van Oerle, Henri M Spronk, Isabelle C Van Gelder
Journal: Circulation (2016)

Background: Atrial fibrillation (AF) is associated with thromboembolic complications. Whether the prothrombotic state is due to AF itself or is caused by coexistent cardiovascular diseases remains ...
Pharmaceutical Company Payments to Executive Board Members of Professional Medical Associations in Japan
Authors: Hiroaki Saito, Akihiko Ozaki, Yasuma Kobayashi, Toyoaki Sawano, Tetsuya Tanimoto
Journal: JAMA Internal Medicine (2019)

more likely to have shorter drug trajectories starting after 2000, to be primary opioid analgesic users who transitioned to heroin, and to be less likely to have histories of opioid agonist treatment. 5,6The distinct age distribution and drug involvement of overdose deaths among New York City blacks, Latinos, and whites, along with complementary evidence about drug use trajectories, highlight the need for heterogeneous approaches to treatment and the equitable allocation of treatment and health care resources to reach diverse populations at risk of overdose.
Is recent decline in breast cancer incidence equal across different US racial groups
Authors: Dezheng Huo, Olufunmilayo Olopade
Journal: Cancer Research (2008)

3839  Abstract 3839 has been selected for inclusion in the AACR’s Annual Meeting press program and is therefore embargoed until date and time of press briefing or scientific presentation, whichever comes first. The abstract is scheduled for scientific presentation and will be posted to this site at or after the following date and time: 4/15/2008 8:00 AM.
Methionine, choline and betaine in oral solution for the treatment of alcoholic fatty liver: results of a multicenter randomized double-blind clinical trial
Authors: Edna Strauss, Luiz Carlos da Costa Gayotto, Antonio Carlos Vitalli, Luis Guilherme Lyra, Carlos Sandoval Goncalves, Vitorino Spinelli Barreto, Edson Cartapacci Silva, Maria Lucia Ferraz, Steve Aleynik, Charles Lieber, Eugene R. Schiff
Journal: Hepatology (1999)
Mind the gaps: Clinical trial concepts to address unanswered questions in aeroallergen immunotherapy—An NIAID/AHRQ Workshop
Authors: Lisa M. Wheatley, Robert Wood, Kari Nadeau, Andrew Liu, Edward Zoratti, Leonard Bacharier, Erica Brittain, Moises Calderon, Thomas Casale, Bradley Chipps, Linda Cox, Peter S. Creticos, Manisha Desai, Sten Dreborg, Stephen Durham, Peter J. Gergen, Rebecca Gruchalla, Harold Nelson, Robyn E. O'Hehir, Marshall Plaut, Julie M. Schwaninger, Stephen Tilles, Brian Vickery, Kim M. Wittenberg, Alkis Togias
Journal: Journal of Allergy and Clinical Immunology (2019)
Precision Medicine vs Preventive Medicine
Authors: Muin J. Khoury
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications 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 2023 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
Evidence-based medicine and infertility treatment
Authors: Sjoerd Repping
Journal: The Lancet (2019)

Intracytoplasmic sperm injection (ICSI) is a procedure that is used to help couples with fertility problems achieve parenthood. Initially developed for couples with severely diminished sperm counts,1 it is increasingly used as the method of choice for couples with fertility problems who are undergoing in-vitro fertilisation (IVF) treatment, despite the available data suggesting that IVF is superior to ICSI in couples with normal sperm counts.2 ICSI differs from IVF in that a single sperm is selected by a trained embryologist and directly injected into the oocyte, rather than letting fertilisation take place unaided after adding a few thousand motile sperm to a single oocyte.
Whole Exome Sequencing of Residual Disease in Multiple Myeloma: Searching for Novel Therapeutic Targets
Authors: Martina Zátopková, Tereza Sevcikova, Zuzana Kufova, Katerina Growkova, Jana Filipova, Tomas Jelinek, Lucie Říhová, Renata Bezděková, Fedor Kryukov, Jana Smejkalová, Jiri Minarik, Vladimir Maisnar, Martin Mistrik, Ludek Pour, Alexandra Jungova, Michal Šimíček, Giovanni Stracquadanio, Roman Hajek
Journal: Blood (2018)
Abstract 14969: Echocardiographic Analysis of Left Ventricular Function in Stress-Challenged Aged Mice: Effects of Gender (Sex) and Menopause
Authors: Candice Baker, Chaunhi Van, Rebekah Katsandris, Steven Ebert
Journal: Circulation (2013)

Stress-induced cardiomyopathies such as Tako-Tsubo or Broken-Heart Syndrome predominantly afflict post-menopausal women (greater than 82% of such cases) who have experienced a sudden emotional shoc...
Stress ulcer prophylaxis with proton pump inhibitors or histamin-2 receptor antagonists in adult intensive care patients: a systematic review with meta-analysis and trial sequential analysis
Authors: Marija Barbateskovic, Søren Marker, Anders Granholm, Carl Thomas Anthon, Mette Krag, Janus Christian Jakobsen, Anders Perner, Jørn Wetterslev, Morten Hylander Møller
Journal: Intensive Care Medicine (2019)
MG53, A Novel Regulator of KChIP2 and <i>I</i> <sub>to,f</sub> , Plays a Critical Role in Electrophysiological Remodeling in Cardiac Hypertrophy
Authors: Wenjuan Liu, Gang Wang, Cuicui Zhang, Wenwen Ding, Wanwen Cheng, Yizhi Luo, Chaoliang Wei, Jie Liu
Journal: Circulation (2019)

KChIP2 (K+ channel interacting protein) is the auxiliary subunit of the fast transient outward K+ current ( Ito,f) in the heart, and insufficient KChIP2 expression induces Ito,f downregulation and arrhythmogenesis in cardiac hypertrophy. Studies have shown muscle-specific mitsugumin 53 (MG53) has promiscuity of function in the context of normal and diseased heart. This study investigates the possible roles of cardiac MG53 in regulation of KChIP2 expression and Ito,f, and the arrhythmogenic potential in hypertrophy.MG53 expression is manipulated by genetic ablation of MG53 in mice and adenoviral overexpression or knockdown of MG53 by RNA interference in cultured neonatal rat ventricular myocytes. Cardiomyocyte hypertrophy is produced by phenylephrine stimulation in neonatal rat ventricular myocytes, and pressure overload-induced mouse cardiac hypertrophy is produced by transverse aortic constriction.KChIP2 expression and Ito,f density are downregulated in hearts from MG53-knockout mice and MG53-knockdown neonatal rat ventricular myocytes, but upregulated in MG53-overexpressing cells. In phenylephrine-induced cardiomyocyte hypertrophy, MG53 expression is reduced with concomitant downregulation of KChIP2 and Ito,f, which can be reversed by MG53 overexpression, but exaggerated by MG53 knockdown. MG53 knockout enhances Ito,f remodeling and action potential duration prolongation and increases susceptibility to ventricular arrhythmia in mouse cardiac hypertrophy. Mechanistically, MG53 regulates NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity and subsequently controls KChIP2 transcription. Chromatin immunoprecipitation demonstrates NF-κB protein has interaction with KChIP2 gene. MG53 overexpression decreases, whereas MG53 knockdown increases NF-κB enrichment at the 5' regulatory region of KChIP2 gene. Normalizing NF-κB activity reverses the alterations in KChIP2 in MG53-overexpressing or knockdown cells. Coimmunoprecipitation and Western blotting assays demonstrate MG53 has physical interaction with TAK1 (transforming growth factor-b [TGFb]-activated kinase 1) and IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), critical components of the NF-κB pathway.These findings establish MG53 as a novel regulator of KChIP2 and Ito,f by modulating NF-κB activity and reveal its critical role in electrophysiological remodeling in cardiac hypertrophy.
Abstract 17687: Myocardial Oxidative Stress, Urinary 8-hydroxy-2’-deoxyguanosine, is Associated With Sustained Ventricular Tachycardia in Patient With Active Cardiac Sarcoidosis
Authors: Hironori Ishiguchi, Shigeki Kobayashi, Michiaki Kohno, Takuma Nanno, Takeki Myoren, Seiko Oda, Hiroki Tateishi, Mamoru Mochizuki, Tetsuro Oda, Jutaro Yamada, Takayuki Okamura, Masafumi Yano
Journal: Circulation (2016)

Background: Recently, we reported that urinary 8-hydroxy-2’-deoxyguanosine (U-8-OHdG), an oxidative stress marker, reflected the inflammatory activity of cardiac sarcoidosis (CS). We investigated w...
Long-term Health-related Quality of Life in Patients Treated With Subcutaneous C1-Inhibitor Replacement Therapy for the Prevention of Hereditary Angioedema Attacks
Authors: William R. Lumry, Timothy J. Craig, Markus A.K. Magerl, Henriette Farkas, John-Philip Lawo, Joseph Chiao, Thomas Machnig
Journal: Journal of Allergy and Clinical Immunology (2019)
Bilateral versus Single Internal-Thoracic-Artery Grafts at 10 Years
Authors: David P. Taggart, Umberto Benedetto, Stephen Gerry, Douglas G. Altman, Alastair M. Gray, Belinda Lees, Mario Gaudino, Vipin Zamvar, Andrzej Bochenek, Brian Buxton, Cliff Choong, Stephen Clark, Marek Deja, Jatin Desai, Ragheb Hasan, Marek Jasinski, Peter O’Keefe, Fernando Moraes, John Pepper, Siven Seevanayagam, Catherine Sudarshan, Uday Trivedi, Stanislaw Wos, John Puskas, Marcus Flather
Journal: New England Journal of Medicine (2019)

Multiple arterial grafts may result in longer survival than single arterial grafts after coronary-artery bypass grafting (CABG) surgery. We evaluated the use of bilateral internal-thoracic-artery grafts for CABG.
Part 1: Executive Summary
Authors: Robert W. Neumar, Michael Shuster, Clifton W. Callaway, Lana M. Gent, Dianne L. Atkins, Farhan Bhanji, Steven C. Brooks, Allan R. de Caen, Michael W. Donnino, Jose Maria E. Ferrer, Monica E. Kleinman, Steven L. Kronick, Eric J. Lavonas, Mark S. Link, Mary E. Mancini, Laurie J. Morrison, Robert E. O’Connor, Ricardo A. Samson, Steven M. Schexnayder, Eunice M. Singletary, Elizabeth H. Sinz, Andrew H. Travers, Myra H. Wyckoff, Mary Fran Hazinski
Journal: Circulation (2015)

The process used to generate the 2015 AHA Guidelines Update for CPR and ECC was significantly different from the process used in prior releases of the Guidelines, and marks the planned transition from a 5-year cycle of evidence review to a continuous evidence evaluation process.The AHA continues to partner with the International Liaison Committee on Resuscitation (ILCOR) in the evidence review process.However, for 2015, ILCOR prioritized topics for systematic review based on clinical significance and availability of new
Zinc Metabolism in Hepatic Dysfunction
Authors: Bert L. Vallee, Warren E. C. Wacker, Anthony F. Bartholomay, Frederic L. Hoch
Journal: New England Journal of Medicine (1957)

THE functional role of zinc has been investigated in experimental systems of varying biologic complexity.1 In previous investigations in this laboratory, the analysis of highly purified enzymes has resulted in the detection of zinc in several dehydrogenases and in carboxypeptidase.2 3 4 5 Two of these, alcohol dehydrogenase and glutamic dehydrogenase, are crystallized from liver,6 , 7 where they occur in subcellular fractions.8 These fractions contain considerable quantities of zinc.9 Chemical, kinetic and spectroscopic studies have shown that zinc is an active enzymatic site in these enzymes, and that its presence is indispensable to their activity.10 , 11 The assessment of these biochemical findings in terms of . . .
Ratify (Alliance 10603): Prognostic Impact of FLT3 tyrosine Kinase Domain (TKD) and NPM1 Mutation Status in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Treated with Midostaurin or Placebo Plus Standard Chemotherapy
Authors: Maria Teresa Voso, Richard A. Larson, Thomas Prior, Guido Marcucci, Dan Jones, Jürgen Krauter, Michael Heuser, Serena Lavorgna, Josep Nomdedeu, Susan M. Geyer, Rebecca Klisovic, Andrew H Wei, Jorge Sierra, Miguel A. Sanz, Joseph M. Brandwein, Theo M de Witte, Joop H. Jansen, Dietger Niederweiser, Frederick R. Appelbaum, Bruno C. Medeiros, Martin S. Tallman, Richard F. Schlenk, Arnold Ganser, Sergio Amadori, Yuan Cheng, Insa Gathmann, Eva Tiecke, Christian Thiede, Konstanze Döhner, Hartmut Döhner, Richard M. Stone, Clara D. Bloomfield, Francesco Lo-Coco
Journal: Blood (2018)
Sequentially inducible mouse models reveal that Npm1 mutation causes malignant transformation of Dnmt3a-mutant clonal hematopoiesis
Authors: Matthew A. Loberg, Rebecca K. Bell, Leslie O. Goodwin, Elizabeth Eudy, Linde A. Miles, Jennifer M. SanMiguel, Kira Young, David E. Bergstrom, Ross L. Levine, Rebekka K. Schneider, Jennifer J. Trowbridge
Journal: Leukemia (2019)

Clonal hematopoiesis (CH) is a common aging-associated condition with increased risk of hematologic malignancy. Knowledge of the mechanisms driving evolution from CH to overt malignancy has been hampered by a lack of in vivo models that orthogonally activate mutant alleles. Here, we develop independently regulatable mutations in DNA methyltransferase 3A (Dnmt3a) and nucleophosmin 1 (Npm1), observed in human CH and AML, respectively. We find Dnmt3a mutation expands hematopoietic stem and multipotent progenitor cells (HSC/MPPs), modeling CH. Induction of mutant Npm1 after development of Dnmt3a-mutant CH causes progression to myeloproliferative disorder (MPD), and more aggressive MPD is observed with longer latency between mutations. MPDs uniformly progress to acute myeloid leukemia (AML) following transplant, accompanied by a decrease in HSC/MPPs and an increase in myeloid-restricted progenitors, the latter of which propagate AML in tertiary recipient mice. At a molecular level, progression of CH to MPD is accompanied by selection for mutations activating Ras/Raf/MAPK signaling. Progression to AML is characterized by additional oncogenic signaling mutations (Ptpn11, Pik3r1, Flt3) and/or mutations in epigenetic regulators (Hdac1, Idh1, Arid1a). Together, our study demonstrates that Npm1 mutation drives evolution of Dnmt3a-mutant CH to AML and rate of disease progression is accelerated with longer latency of CH.
KRAS mutation as a predictor for cause-specific survival in early- versus late-onset colorectal cancer: A United States population-based study.
Authors: Albert Y. Lin, Amanda R Kahl, Jennifer Y. Pan, Joshua Lo, Winifred Tung, George A. Fisher, Mary E. Charlton
Journal: Journal of Clinical Oncology (2019)

580 Background: While the overall incidence rates for colorectal cancer (CRC) —the third leading cancer diagnosis in the U.S.—have been decreasing over the last several decades, incidence rates for early-onset (EO, age 20-49 years) CRC have shown an upward trend. Multiple studies have documented mutations in KRAS proto-oncogene (KRAS) as a poor prognostic factor in sporadic CRC, but its impact on EO versus late-onset (LO, age &gt; 49 years) CRC is unclear. Methods: Surveillance, Epidemiology, and End Results (SEER) Program data were queried to identify pathologically-confirmed CRC cases tested for KRAS and diagnosed between 2010 and 2015. Demographic, histologic, and KRAS data were compared between EO and LO using Chi-square tests. Kaplan-Meier and Cox proportional hazards models were used to estimate cause-specific survival (CSS) and examine factors associated with CSS. Results: Of 202,173 CRC cases, 3,842 EO and 17,819 LO CRC cases had KRAS testing with a KRAS mutation frequency of 40% and 41%, respectively. Compared with LO tumors harboring mutated KRAS, EO tumors with KRAS mutations were more frequently found in females (52% vs. 45%, P &lt; 0.001), left-sided (LS) or rectal cancers (62% vs. 48%, P &lt; 0.001), stage III/IV (89% vs. 81%, P &lt; 0.001), and grade III/IV (21% vs. 18%, P = 0.038). Compared to CSS in EO with KRAS mutation, LO with KRAS mutation was associated with worse prognosis—with an overall hazard ratio (HR) of 1.21 (95% CI, 1.15-1.27, P &lt; 0.0001). Results [HR (95% CI)] from Cox analyses on the effects of KRAS mutation on CSS, stratified by sidedness, are shown below. Conclusions: Despite EO CRC carrying worse prognostic factors than LO CRC, it confers better CSS than LO CRC. EO CRC is distinct from LO CRC in clinical and pathological features, in addition to its response to mutant KRAS. Mutated KRAS is an independent prognostic factor in LS colon and rectal cancers among the LO, but not in the EO population. [Table: see text]
Real world eligibility for cabozantinib (C), regorafenib (Reg), and ramucirumab (Ram) in hepatocellular carcinoma (HCC) patients after sorafenib (S).
Authors: Andrea S. Fung, Vincent C. Tam, Daniel E. Meyers, Hao-Wen Sim, Jennifer J. Knox, Valeriya O. Zaborska, Janine Marie Davies, Yoo-Joung Ko, Eugene Batuyong, Winson Y. Cheung, Haider Samawi, Richard M. Lee-Ying
Journal: Journal of Clinical Oncology (2019)

422 Background: The CELESTIAL, RESORCE, and REACH-2 trials showed survival benefit of C, Reg, and Ram, respectively, when given after S to HCC patients. However, strict eligibility criteria (SEC) may limit generalizability. In clinical practice, modified eligibility criteria (MEC) may be used to offer treatments to select patients with slightly worse performance status (ECOG 2) or limited liver dysfunction (Child-Pugh (CP) B7). This study evaluated which patients in the real world would be eligible for these new treatments using SEC and MEC, and their prognostic impact. Methods: HCC patients who received S between 01/2008-06/2017 in British Columbia, Alberta, Princess Margaret Cancer Centre, and Sunnybrook Cancer Centre in Canada were included. Clinical, pathologic, laboratory and outcome data were collected. Patients were classified as eligible or ineligible based on available CELESTIAL, RESORCE, REACH-2 clinical trial SEC or MEC. Median overall survival (mOS) for these groups was assessed using the Kaplan-Meier method. Results: A total of 730 patients were identified. Using SEC, only 13.1% of patients would be eligible for C, Reg, or Ram (table). Expanding eligibility to include patients who meet MEC increased the proportion of eligible patients to 31.7%. Patients who met SEC had longer mOS compared to those who were ineligible. The most common reasons for not meeting SEC across all 3 trials were ECOG ≥ 2 (61.7%) and CP ≥ B (63.9%). Higher ineligibility for Reg or Ram was likely driven by strict trial-specific criteria, with 28.0% of patients ineligible for Reg due to S intolerance and 58.9% ineligible for Ram due to AFP &lt; 400. Conclusions: Only a small proportion of real-world HCC patients would be eligible for C, Reg, or Ram based on SEC. More than twice as many patients would likely receive treatment if MEC were applied. If MEC are adopted, ongoing real-world evidence generation will be important to evaluate outcomes in these unstudied patient groups. [Table: see text]
Differentiation of human pluripotent stem cells into neurons or cortical organoids requires transcriptional co-regulation by UTX and 53BP1
Authors: Xiaoyang Yang, Beisi Xu, Brett Mulvey, Myron Evans, Samuel Jordan, Yong-Dong Wang, Vishwajeeth Pagala, Junmin Peng, Yiping Fan, Arishna Patel, Jamy C. Peng
Journal: Nature Neuroscience (2019)