tbuckley/cabot-search huggingface dataset:
Randomized phase II study of two different doses of AVE0005 (VEGF Trap, aflibercept) in patients (pts) with metastatic renal cell carcinoma (RCC): An ECOG-ACRIN study [E4805].
Authors: Roberto Pili, Judith Manola, Michael Anthony Carducci, Janice P. Dutcher, Leonard Joseph Appleman, David L. Groteluschen, Robert S. DiPaola
Journal: Journal of Clinical Oncology (2015)

4549 Background: AVE0005 (VEGF Trap), or aflibercept, is a recombinantly-produced fusion protein consisting of human VEGF receptor extracellular domains fused to the Fc portion of human IgG1 that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell RCC. The recommended Phase 2 dose was 4 mg/kg but several pts treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial. Methods: Eligible pts had metastatic clear cell RCC and previous treatments including prior exposure to a VEGF TKI. Pts were stratified on prior immunotherapy (IL2/IFN) and MSKCC Risk Category. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg could crossover to 4 mg/kg at progression. The primary endpoint was proportion alive and progression-free at 8 weeks. A 2-stage design was used for each arm with 33 and 24 eligible pts/arm enrolled in stages 1 and 2. If 17 pts were alive and PF at 8 wks or an objective response was observed, an arm would continue to stage 2, and if 34 of 57 eligible pts were PF at 8 wks, the arm would be considered for further study. This design had 91% power and 10% Type I error. Results: 94 pts were enrolled, 59 and 35 to 4 mg and 1 mg doses respectively. Median age was 61 with 72% male, 96% white, and 72% with 1 prior tx (most commonly sunitinib). 16 eligible pts crossed over at progression to the 4 mg dose. The most common adverse events were hypertension, proteinuria, and fatigue. Only 4 pts reported Grade 4 or higher toxicity. With 36/59 (61%) pts PF at 8 wks, the 4-mg/kg dose met protocol specified efficacy criteria. Conclusions: At a dose level of 4mg/kg, 61% of patients were progression free at 8 weeks, meeting pre-specified criteria. Aflibercept at a dose of 4 mg/kg is active in previously treated ccRCC and may be worthy of further study. Clinical trial information: NCT00357760. Arm A (4 mg/kg) Arm B (1 mg/kg) Crossover Enrolled 59 35 17 Eligible 59 32 16 PF at 8 Wks 36 (61.0%) 15 (42.9%) 90% CI 49.5 – 71.7% 28.6 – 58.1% Median PFS (wks) 10.9 8.3 18.1 90% CI (wks) 8.7 – 15.4 7.9 – 9.6 8.0 – 24.1 ORR 1.7% 3.1% 90% CI 0.1 – 7.8% 0.2 – 14.0%
Prognostic value of plasma cytokines in metastatic testicular germ cell tumors (TGCTs).
Authors: Daniela Svetlovska, Vera Miskovska, Dana Cholujova, Jan Luha, Patrik Palacka, Vanda Usakova, Jana Obertova, Zuzana Sycova-Mila, Michal Chovanec, Jan Rajec, Bibiana Vertakova-Krakovska, Paulina Gronesova, Peter Bujdak, Dalibor Ondrus, Stanislav Spanik, Jozef Mardiak, Michal Mego
Journal: Journal of Clinical Oncology (2015)

e15558 Background: Accumulating data suggest that the plasma levels of some cytokines might reflect the activity of the immune system against the tumor and correlate to prognosis. Cytokines may influence disease progression through their tumor-promoting and/or tumor-suppressive properties. Plasma cytokines can be easily identified and thus might serve as a biomarker to predict survival in cancer patients. Our aim was to find out prognostic value of plasma cytokines in patients with TGCTs. Methods: In our prospective study we enrolled 60 treatment naive metastatic TGCTs patients. All patients were treated with platinum based chemotherapy and received G-CSF support after chemotherapy. 51 plasma cytokines were analyzed at baseline on day 1 (n = 60) and on day 22 (n = 34) of the cycle 1 chemotherapy using multiplex bead arrays (Human Group I and II cytokine panels and TGF beta by Bio-Plex 200 system (Bio-Rad Laboratories, Hercules, CA). Group was dichotomized according to median cytokine value. Kaplan-Meier plots and the log-rank tests were used to compare groups with PFS and OS. Results: Median follow-up was 39.0 month (0.9-53.9 months), 8.3% patients experienced disease progression and 6.7% patients died. Patients with elevated pretreatment levels of IL-2ra, IL-16, GRO-α, HGF, MCP-3, MIG, β-NGF had significantly shorter OS. Higher levels of IL-12(p40) detected on day 22 of 1stcycle of chemotherapy were significantly associated with shorter PFS and OS. Conclusions: Elevated values of several cytokines predicted decreased OS and/or PFS in metastatic TGCTs patients. We suggest that these data could help to identify patients with higher risk of relapse that could be candidate for new treatment approach.
The Nutrition of a Cancer Patient: Perspective Cohort Study on The Variation of the Consume of Meals by Location and in Caregivers Presence
Authors: A. Guerra, A. Bin, C. Sacco, G. Troiero, S. Mattiussi, F. Oliviero, S. Coletti, E. Gobbo, F. Pez, F. Gatti
Journal: Annals of Oncology (2015)
Double Transplantation with Melphalan (200 mg/m2) Compared with Triple Transplantation with Intermediate Dose Melphalan (100 mg/m2) in Patients with Multiple Myeloma
Authors: Heinz Ludwig, Ivan Spicka, Werner Linkesch, Richard Greil, Hedwig Kasparu, Eberhard Gunsilius, Josef Thaler, Johannes Drach, Ingrid Kuhn, Adalbert Weiβmann, Axel Hinke
Journal: Blood (2008)
Barbara (Basia) Howells
Authors: Hilary Howells, Jane Howells
Journal: BMJ (2016)

Basia Kaja Zamoyska was born in Warsaw and came to England aged 7 in 1940. This was some months after the invasion of Poland, and she arrived with her parents in a coal boat, crossing the Channel from France to Falmouth.

The family had little money, and Farnborough Hill Convent gave her a virtually free education in homage to her native …
Aspirin Instead of Oral Anticoagulant Prescription in Atrial Fibrillation Patients at Risk for Stroke
Authors: Jonathan C. Hsu, Thomas M. Maddox, Kevin Kennedy, David F. Katz, Lucas N. Marzec, Steven A. Lubitz, Anil K. Gehi, Mintu P. Turakhia, Gregory M. Marcus
Journal: Journal of the American College of Cardiology (2016)
Routine skull films in hospitalized psychiatric patients
Authors: J F Delaney
Journal: American Journal of Psychiatry (1976)

Skull films were taken routinely for a sample consisting of all inpatients at a psychiatric facility over a 5-year period (N = 2,943). The skull series revealed some abnormalities in 17.3% of the patients and significant abnormalities in 2.4%. The author concludes that the results of this trial do not justify routine skull films for psychiatric patients in the absence of neurological symptoms.
The Challenging Task of Improving the Recovery of ICU Survivors
Authors: Shannon L. Goddard, Neill K. J. Adhikari
Journal: JAMA (2016)

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
Integrating the Internship into Ophthalmology Residency Programs
Authors: Thomas A. Oetting, Eduardo C. Alfonso, Anthony Arnold, Louis B. Cantor, Keith Carter, Oscar A. Cruz, Steven Feldon, Bartly Mondino, David W. Parke, Suzann Pershing, Tara Uhler, Nicholas J. Volpe
Journal: Ophthalmology (2016)
Long-Term Follow-up of Hemophilia a Patients Who Previously Showed Complete or Partial Success in Immune Tolerance Induction Therapy with a Single Plasma-Derived FVIII/VWF Product: Long-Term ITI Study
Authors: Víctor Jiménez-Yuste, Johannes Oldenburg, Savita Rangarajan, Roser Peiró, Elena Santagostino
Journal: Blood (2015)
The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis
Authors: Kristina B. Schoedel, Mina N. F. Morcos, Thomas Zerjatke, Ingo Roeder, Tatyana Grinenko, David Voehringer, Joachim R. Göthert, Claudia Waskow, Axel Roers, Alexander Gerbaulet
Journal: Blood (2016)
Curtains
Authors: Nir Lipsman
Journal: JAMA (2009)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
MEF2D Transduces Microenvironment Stimuli to ZEB1 to Promote Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer
Authors: Li Su, Yongli Luo, Zhi Yang, Jing Yang, Chao Yao, Feifei Cheng, Juanjuan Shan, Jun Chen, Fangfang Li, Limei Liu, Chungang Liu, Yanmin Xu, Lupin Jiang, Deyu Guo, Jesus Prieto, Matías A. Ávila, Junjie Shen, Cheng Qian
Journal: Cancer Research (2016)

Epithelial-mesenchymal transition (EMT) is an essential mechanism of metastasis, including in colorectal cancer. Although EMT processes are often triggered in cancer cells by their surrounding microenvironment, how EMT-relevant genes control these processes is not well understood. In multiple types of cancers, the transcription factor MEF2D has been implicated in cell proliferation, but its contributions to metastasis have not been addressed. Here, we show MEF2D is overexpressed in clinical colorectal cancer tissues where its high expression correlates with metastatic process. Functional investigations showed that MEF2D promoted cancer cell invasion and EMT and that it was essential for certain microenvironment signals to induce EMT and metastasis in vivo Mechanistically, MEF2D directly regulated transcription of the EMT driver gene ZEB1 and facilitated histone acetylation at the ZEB1 promoter. More importantly, MEF2D responded to various tumor microenvironment signals and acted as a central integrator transducing multiple signals to activate ZEB1 transcription. Overall, our results define a critical function for MEF2D in upregulating EMT and the metastatic capacity of colorectal cancer cells. Further, they offer new insights into how microenvironment signals activate EMT-relevant genes and deepen the pathophysiologic significance of MEF2D, with potential implications for the prevention and treatment of metastatic colorectal cancer. Cancer Res; 76(17); 5054-67. ©2016 AACR.
Reporting Magnetic Resonance Imaging in Men on Active Surveillance for Prostate Cancer: The PRECISE Recommendations—A Report of a European School of Oncology Task Force
Authors: Caroline M. Moore, Francesco Giganti, Peter Albertsen, Clare Allen, Chris Bangma, Alberto Briganti, Peter Carroll, Masoom Haider, Veeru Kasivisvanathan, Alex Kirkham, Laurence Klotz, Adil Ouzzane, Anwar R. Padhani, Valeria Panebianco, Peter Pinto, Philippe Puech, Antti Rannikko, Raphaele Renard-Penna, Karim Touijer, Baris Turkbey, Heinrik van Poppel, Riccardo Valdagni, Jochen Walz, Ivo Schoots
Journal: European Urology (2016)
Thirty Years of Saying NO
Authors: Paul M. Vanhoutte, Yingzi Zhao, Aimin Xu, Susan W.S. Leung
Journal: Circulation Research (2016)

Endothelial cells control vascular tone by releasing nitric oxide (NO) produced by endothelial NO synthase. The activity of endothelial NO synthase is modulated by the calcium concentration and by post-translational modifications (eg, phosphorylation). When NO reaches vascular smooth muscle, soluble guanylyl cyclase is its primary target producing cGMP. NO production is stimulated by circulating substances (eg, catecholamines), platelet products (eg, serotonin), autacoids formed in (eg, bradykinin) or near (eg, adiponectin) the vascular wall and physical factors (eg, shear stress). NO dysfunction can be caused, alone or in combination, by abnormal coupling of endothelial cell membrane receptors, insufficient supply of substrate ( l -arginine) or cofactors (tetrahydrobiopterin), endogenous inhibitors (asymmetrical dimethyl arginine), reduced expression/presence/dimerization of endothelial NO synthase, inhibition of its enzymatic activity, accelerated disposition of NO by reactive oxygen species and abnormal responses (eg, biased soluble guanylyl cyclase activity producing cyclic inosine monophosphate) of the vascular smooth muscle. Major culprits causing endothelial dysfunction, irrespective of the underlying pathological process (aging, obesity, diabetes mellitus, and hypertension), include stimulation of mineralocorticoid receptors, activation of endothelial Rho-kinase, augmented presence of asymmetrical dimethyl arginine, and exaggerated oxidative stress. Genetic and pharmacological interventions improve dysfunctional NO-mediated vasodilatations if protecting the supply of substrate and cofactors for endothelial NO synthase, preserving the presence and activity of the enzyme and reducing reactive oxygen species generation. Common achievers of such improvement include maintained levels of estrogens and increased production of adiponectin and induction of silent mating-type information regulation 2 homologue 1. Obviously, endothelium-dependent relaxations are not the only beneficial action of NO in the vascular wall. Thus, reduced NO-mediated responses precede and initiate the atherosclerotic process.
Review: In diabetes, benefits of lowering BP depend on baseline BP being 140 mm Hg or more
Authors: Laura Larrea Mantilla, Victor M. Montori
Journal: Annals of Internal Medicine (2016)

Source Citation Brunström M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ. 2016;352:i717. 26920333
Continued Risk of Relapse Independent of Treatment Modality in Limited-Stage Diffuse Large B-Cell Lymphoma: Final and Long-Term Analysis of Southwest Oncology Group Study S8736
Authors: Deborah M. Stephens, Hongli Li, Michael L. LeBlanc, Soham D. Puvvada, Daniel Persky, Jonathan W. Friedberg, Sonali M. Smith
Journal: Journal of Clinical Oncology (2016)

Purpose Utility of combined-modality therapy for patients with limited-stage diffuse large B-cell lymphoma (DLBCL) was shown in the Southwest Oncology Group (SWOG) S8736 study, where three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus radiotherapy (CHOP3RT) improved 5-year progression-free (PFS) and overall survival (OS) compared with eight cycles of CHOP (CHOP8). Subsequent analysis showed an unexpected overlap of the PFS curves. We aimed to confirm and investigate this observation by performing long-term analysis of SWOG S8736 and evaluating these data alongside data from similar patients receiving rituximab and CHOP3RT (SWOG S0014 study). Patients and Methods A subset of patients with limited-stage DLBCL randomly assigned to CHOP8 (n = 150) or CHOP3RT (n = 158) in S8736 was analyzed along with a 56-patient subset treated in S0014 for long-term PFS and OS. Results Median follow-up in S8736 was 17.7 years. In patients receiving CHOP8 and CHOP3RT, median PFS was 12.0 (95% CI, 8.8 to 14.3) and 11.1 years (95% CI, 8.9 to 14.4), respectively. There were no statistically significant differences in PFS between the groups (P = .73). Median OS was 13.0 (95% CI, 10.4 to 15.2) and 13.7 years (95% CI, 11.1 to 19.4) for patients treated with CHOP8 and CHOP3RT, respectively. Similarly, there were no statistically significant differences in OS between the groups (P = .38). With a median follow-up time 12 years in S0014, 5- and 10-year OS were 82% and 67%, respectively, with a persistent pattern of relapse despite the addition of rituximab. Conclusion Although 5-year PFS and OS were improved after early analysis in patients with limited-stage DLBCL receiving CHOP3RT versus CHOP8, extended survival data showed similar PFS and OS, with continuous treatment failure. The addition of rituximab (S0014) to combined-modality therapy did not mitigate the continued relapse risk, underscoring the value of prolonged clinical trial patient observation and possible unique biology of limited-stage DLBCL.
Silent aspiration in patients with exacerbation of COPD
Authors: Zeguang Zheng, Zhida Wu, Ni Liu, Ping Chen, Peng Hou, Xinni Wang, Yimin Fu, Weijian Liang, Rongchang Chen
Journal: European Respiratory Journal (2016)

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to aspiration, probably due to discoordination between breathing and swallowing, cricopharyngeal muscle dysfunction, and changes in lung volume [1, 2]. Terada et al . [3] found a significantly higher prevalence of an abnormal swallowing reflex in patients with COPD than in healthy controls. Shaker et al . [4] found that patients with acute exacerbation of COPD (AECOPD) have a higher risk of aspiration. In this cross-sectional study, using the technetium-99m–sulfur colloid (99mTc-SC) salivary scintigraphy method that is believed to be more sensitive than techniques using in previous studies, the prevalence and risk factors of silent aspiration in hospitalised AECOPD patients was studied. Radionuclide imaging of silent aspiration <http://ow.ly/s3pz300hiSN> We would like to express our gratitude to all of those who assisted with the preparation of this manuscript, particularly to Guangqiao Zeng (State Key Laboratory of Respiratory Disease, Guangzhou, China) for helpful contributions to the translation and editing of this article.
Case 14-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Leonard Ellman, Benjamin Castleman
Journal: New England Journal of Medicine (1973)

Presentation of Case First admission. An 81-year-old woman was admitted to the hospital because of anemia.She was well and vigorous until three years previously, when anorexia developed after the death of her husband, with gradual loss of 30 kg in weight. Three months before entry she began to experience fatigue, dizziness and gradually progressive exertional dyspnea. For several weeks before admission dyspnea and chest pain occurred on walking across a room, with three-pillow orthopnea. Ten days before entry a physician prescribed iron and digoxin, without benefit.There was no history of prior chest pain, edema, anemia, bleeding or bruising, . . .
Effects of methylphenidate (MP) on symptom couplets associated with cancer-related fatigue (CRF) in patients with advanced cancer.
Authors: Sriram Yennu, Janet L. Williams, Minjeong Park, Diane D Liu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

191 Background: Psychostimulant clinical trials on CRF in pts with advanced cancer suggest mixed effects on CRF. The aim of this study was to determine the effects of MP and placebo (PL) on the pts with clinically significant CRF and associated symptoms such as depression, sedation, or depression and sedation (couplets). Methods: Secondary analysis of pts who received MP as a part of 3 prospective controlled clinical trials on MP for CRF. Pts were categorized one of 4 groups, fatigue+depression (FD), fatigue+ drowsiness (FDR), fatigue+drowsiness+depression (FDDR) or fatigue only (F), and outcomes were change in FACIT-F subscale and ESAS -fatigue scores at Day 8 of treatment with MP and PL. Repeated measures analysis was applied to assess the effects of treatment over time (Day8 – Day0) among the 4 groups on FACIT-F subscale and ESAS fatigue. Results: Of the 322 evaluable pts (34 FD, 100 FDR, 78 FDDR, 107F), at Day 8 there was a significant improvement in the ESAS fatigue in MP compared to PL groups [median (IQR)-2 (-4, -1) vs 2 (-3.5,0),p = 0.03, but the difference in the change of FACIT-F between the groups was not significant [median(IQR) 8(2,17) VS7(0,12), p = 0.09). Repeated measures analysis on FACIT-F with pairwise interactions(Time X Baseline Group, Time X Treatment) shows that regardless of treatment, the increase of FACIT-F from Day0 to Day8 was significantly different between FD and F (p = 0.001) and between FDDR and F (p = 0.03).However the change over time was not significantly different between two treatment groups (p = 0.23). Furthermore, the repeated measure analysis including three term interactions(Time X Treatment X Baseline Group) indicates no significant the treatment effect on FACIT-F over time is not significantly different among the four groups (p = 0.89). Similarly, there is no significant treatment effect in ESAS fatigue score over time among the four groups. Conclusions: Although there was a general improvement in CRF (FACIT-F) scores over time, there was no significant treatment effect on this improvement over time among F or FD, or FDR, or FDDR groups defined by fatigue/depression/sedation in the whole study population. Further studies are needed.