tbuckley/cabot-search huggingface dataset:
Tumor-specific circulating cell-free DNA (cfDNA) BRAF mutations (muts) to predict clinical outcome in patients (pts) treated with the BRAF inhibitor dabrafenib (GSK2118436).
Authors: Georgina V. Long, Paolo Antonio Ascierto, Jean Jacques Grob, Omid Hamid, Richard Kefford, Celeste Lebbe, David R. Minor, Antoni Ribas, Dirk Schadendorf, Leslie Anne Fecher, Uwe Trefzer, Nikita Arya, Robert C. Gagnon, Vicki L. Goodman, Anne Siegfried, Jolly Mazumdar, Anne-Marie Martin
Journal: Journal of Clinical Oncology (2012)

8518 Background: Tumor specific cfDNA levels in blood increase with tumor burden and decrease following treatment. cfDNA can harbor muts consistent with the tumor. Thus cfDNA could be a useful biomarker of therapeutic response. BREAK-2, an open label, single arm, Phase II study evaluated efficacy, safety and tolerability of dabrafenib in BRAF V600E/K mut+ metastatic melanoma pts. Exploratory objectives of BREAK-2 were to evaluate whether (i) tumor and cfDNA BRAF muts are correlated; (ii) cfDNA levels correlate with baseline tumor burden and (iii) cfDNA muts predict clinical outcome with dabrafenib. Methods: BRAF mut status was established for 92pts using an allele-specific PCR assay in tumor samples. Baseline plasma samples were available for 91/92 pts. cfDNA BRAF mut status was evaluated by Inostics GmBH using the BEAMing technology. Spearman correlation coefficients (R) were used to determine the association between cfDNA fraction (mut DNA molecules &gt; 0.01%) and estimated baseline tumor burden, calculated by the sum of RECIST measurements of target lesions. Logistic regression and Cox proportional hazards models were used to assess the association between cfDNA mut status and objective response rate (ORR) and progression free survival (PFS), respectively. Results: The overall agreement between tumor and cfDNA BRAF V600E and V600K mut status was 83%, and 96% respectively. Higher cfDNA V600E mut fraction was associated with higher baseline tumor burden (R=0.73; p-value &lt; 0.0001; n=60); lower ORR (O.R. = 0.83; 95% CI = 0.72, 0.96; p-value=0.0134; n=46) and shorter PFS (H.R.=1.09; p-value=0.0006; n=46). Median PFS was 27.4 weeks in the overall V600E pt population (n=76) and 20.0 weeks in the cfDNA V600E pt population (n=46). Otherwise, the response endpoints were comparable between the two populations. There was no correlation between V600K mut fraction (n=14) and any efficacy endpoints. Conclusions: cfDNA was useful for detecting BRAF muts in pts treated with dabrafenib and increasing V600E mut fraction was associated with reduced ORR and shorter PFS, suggesting higher amounts of mut cfDNA in V600E mut+ pts predicts poorer clinical outcome.
Combined Incentives and Restrictions Lead to Better Food Choices
Authors: Anita Slomski
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
Prognostic Impact of the Amount of CD34+ CD38- CD123+ Cells at Diagnosis In Acute Myeloid Leukemia: a Study From the GOELAMS
Authors: François Vergez, Alexa Green, Jérôme Tamburini, Nathalie Gallay, Murielle Roussel, Baptiste Gaillard, Aymeric Neyret, Melanie Pannetier, Nicolas Chapuis, Norbert Ifrah, Francois Dreyfus, Cécile Demur, Catherine Lacombe, Patrick Mayeux, Didier Bouscary, Stéphane Manenti, Christian Récher, Valérie Bardet
Journal: Blood (2010)
THU0308 Hydroxychloroquine Improves Pregnancy Outcome in Women with Antiphospholipid Antibodies without Other Underlying Connective Tissue Disease
Authors: S. Sciascia, S. Baldovino, D. Roccatello, M.J. Cuadrado
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Low-dose aspirin and/or heparins represent the treatment of choice for the management of pregnant women with antiphospholipid antibodies (aPL). However, despite these treatments, maternal, fetal, and neonatal complications related to the presence of aPL may still occur. <h3>Objectives</h3> To assess pregnancy outcome in women with aPL without other underlying connective tissue disease (CTD) who were treated with hydroxychloroquine (HCQ) in addition to conventional treatment during pregnancy. <h3>Methods</h3> Eighty-nine pregnancies in 48 women with persistent aPL were included in this observational, retrospective, cohort study: (group 1) 17 pregnancies that occurred in 13 women were treated with HCQ for at least 6 months before pregnancy, and the therapy continued throughout gestation; (group 2) 72 pregnancies that occurred in 35 women with aPL that were not treated with HCQ were included as controls. All the patients were tested positive for aPL in the absence of conclusive clinical signs/symptoms of CTD. <h3>Results</h3> HCQ-treatment was associated with a higher rate of live births (82% group A vs 58% group B; p=0.05). Placenta-mediated complications (pre-eclampsia and abruption placentae) were not observed in group 1 but occurred in 5 cases of group 2. Pregnancy duration was longer in group 1 than group 2 (36.4 [6–40] vs 33.5 [6–40] weeks; p=0.04). <h3>Conclusions</h3> Despite the limit of the small sample size, our observations support that HCQ may improve pregnancy outcome in women with aPL. <h3>Disclosure of Interest</h3> None declared
FRI0433 Factors Associated with Elevated Acute Phase Reactants in Patients with Recent Inflammatory Back Pain: Impact of C Reactive Protein on The Phenotype of Patients. Data from The Prospective Multicenter French Cohort Desir
Authors: P. Manicki, J. Morel, B. Combe, D. Van der Heijde, C. Lukas
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To determine the prevalence of increased C reactive protein (CRP) in patients with recent inflammatory back pain (IBP) suggestive of spondylarthritis (SpA) and to describe the overall features of these patients. <h3>Methods</h3> The DESIR cohort is a prospective multicenter French cohort of 708 patients with early IBP suggestive of SpA. An abnormal acute phase reactants level was determined based on normal upper range of values determined by centralized assessment of CRP. Data on the baseline demographic characteristics, functional status and quality of life, imaging features and HLA B27 status were compared in patients with and without increased CRP. We studied the total population of 708 patients and the subgroup of patients fulfilling ASAS criteria at the inclusion. Significant parameters in univariate analysis were tested in multivariate models. <h3>Results</h3> The prevalence of increased CRP (&gt;5mg/L) at inclusion in the DESIR cohort was 233/684 (34.1%). The presence of increased CRP was significantly associated (univariate) with a younger age, previous history of arthritis, a history of dactylitis, clinical synovitis, BMD, radiographic sacroiliitis, a higher baseline modified Score of Ankylosing Spondylitis Spinal Score (mSASSS), MRI inflammatory lesions of spine and sacroiliac joints, scores of disease activity including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity (ASDAS-CRP), physical function assessed by Bath Ankylosing Spondylitis Functional Index (BASFI), and health status indicators (Ankylosing Spondylitis Quality of Life, Health Assessment questionnaire for Ankylosing Spondylitis and the Physical Component Score from Short Form 36) in both populations. Increased CRP was associated with the absence of HLA-B27 only in the subgroup of patients fulfilling ASAS criteria. Stepwise multivariate analysis found an association between increased CRP and male gender, younger age, history of arthritis, BMD &gt;25kg.m<sup>2</sup>, radiographic sacroiliitis, mSASSS, MRI inflammation on sacroiliac joints and ASDAS-CRP (p&lt;0,05). <h3>Conclusions</h3> In recent IBP suggestive of SpA, increased CRP is associated with younger age, presence of peripheral articular manifestations, radiologic abnormalities, and both with higher activity and functional disability. Patients with elevated acute phase reactants seem to have a more severe form of the disease. <h3>Disclosure of Interest</h3> None declared
Interaction of a Novel Signaling Protein (AHI-1) with BCR-ABL Modulates BCR-ABL Transforming Activity and Imatinib Response of Chronic Myeloid Leukemia Progenitor Cells.
Authors: Yun Zhao, Leon Zhou, Ashley Ringrose, Ann E.-J. Lin, Erin Kennah, Guoqing Sheng, Xiao-Jiang Li, Ali Turhan, Xiaoyan Jiang
Journal: Blood (2007)
Outcome of Sibling Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantations in Low-Grade B Cell Lymphoproliferative Disorders. A Single Centre Experience.
Authors: Ronan Desmond, Marianna David, Eibhlin Conneally, Paul Browne, Mairead Ni Conghaile, Shaun McCann, Elizabeth Vandenberghe
Journal: Blood (2007)
AB0494 Risk Factors of Heart Disease in Patients with Systemic Lupus Erythematosus
Authors: N.A. Ganiyeva, M.B. Kasymova, F.K. Ziyayeva, E.R. Djurayeva, D.U. Berdiyeva
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Cardio vascular diseases are caused by premature development of atherosclerotic vascular lesions and thrombotic complications and the third leading cause to death in patients with systemic lupus erythematosus (SLE). <h3>Objectives</h3> Identify associated risk factors of cardiovascular disease in patients with SLE. <h3>Methods</h3> A total of 92 patients (9 men and 83 women) with a documented diagnosis of SLE according to the ARA criteria. The age of patients ranged from 18 to 55 years of age, disease duration ranged from 3 to 24 years. More than half part of patients with SLE have a subacute course of the disease (78.6%) and the average level of activity (80.2%). In clinical surveys were taken into account family history of cardiovascular disease, smoking, hypertension, diabetes mellitus (DM), body mass index, menopause in women, stress. It was detected biochemical blood tests to determine the lipid profile - total cholesterol, VLDL cholesterol, LDL cholesterol, HDL cholesterol, triglycerides. Also surveyed cerebral circulation according to Doppler ultrasound of the brachiocephalic vessels (SPL cylinder head). <h3>Results</h3> Classical cardiovascular risk factors (one or more) occurred in 85 (92.3%) patients. Thus, were the predominant dyslipidemia (78.7% of patients), mainly due to triglyceridemia, increase the level of total cholesterol and low density lipoprotein. Hypertension was detected in 32.7% of patients, smoking - 13.6%, overweight - at 45.4%, family history of cardiovascular disease - at 27.2%, diabetes - at 4.5%, menopause in women - 15.8%, stress - 35% of patients. During the cylinder head ultrasound carotid artery vasoconstriction by type was detected in 77.2% of patients. <h3>Conclusions</h3> The results of this study confirm the high probability of the development of atherosclerosis and related complications in SLE patients, which calls for the timely detection and correction of modifiable risk factors. <h3>Disclosure of Interest</h3> None declared
Doctors should nap during night shifts, conference hears
Authors: Abi Rimmer
Journal: BMJ (2016)

Researchers at a conference on the effect of sleep on fitness to work discussed how sleep deprivation can affect patient safety and doctors’ training. Abi Rimmer reports

Junior doctors working night shifts should be allowed to take regular short naps, says Jim Horne, a sleep neuroscientist and emeritus professor of psychophysiology at Loughborough University.

Horne was speaking at a conference held at the Royal Society of Medicine in London on 16 November about the effects of sleep deprivation on workers. He told the conference that a lack of sleep could affect a person’s ability to work and deal with emergencies.

Speaking to BMJ Careers, Horne said that “there’s absolutely no doubt” that junior doctors should be allowed to take short naps. He said, “It’s safer for everyone concerned; it makes the doctor safer to work, it improves patient safety, it reduces accidents, and …
Decreased Generation and Function of CD4+CD25hi T Regulatory Cells in Human STAT5b Deficiency.
Authors: Aileen Cleary, Kari Nadeau, Wenwei Tu, Vivian Hwa, Kira Y. Dionis, Liliana Bezrodnik, Alejandro Teper, Maria Gaillard, Juan J. Heinrich, Alan M. Krensky, Ron G. Rosenfeld, David B. Lewis
Journal: Blood (2005)
The VITAL study: A randomized, double-blind, placebo-controlled, global, phase III study of NEOD001 in patients with AL amyloidosis and cardiac dysfunction.
Authors: Michaela Liedtke, Giampaolo Merlini, Heather Jolie Landau, Ray Comenzo, David C. Seldin, Brendan M. Weiss, Jeffrey A. Zonder, Jackie Walling, Gene Kinney, Marty Koller, Morie A. Gertz
Journal: Journal of Clinical Oncology (2015)

TPS8614 Background: Light chain (AL) amyloidosis is a rare disease caused by the deposition of misfolded proteins that cause dysfunction of vital organs (eg, heart and kidneys). There are no approved therapies. Current therapeutic approaches target the plasma cells that produce the pathogenic light chain proteins and are typically associated with significant adverse effects. Therefore, there is a substantial need for a safe and effective therapy that specifically targets the misfolded light chain proteins responsible for the underlying organ dysfunction. NEOD001 is a monoclonal antibody that targets these misfolded proteins, and it is hypothesized to neutralize circulating soluble protein aggregates and clear insoluble aggregates from organs. In an ongoing phase I/II study in 27 patients with AL amyloidosis and persistent organ dysfunction, NEOD001 was safe and well tolerated, with monthly infusions producing meaningful decreases in cardiac and renal biomarkers by best response. Supported by these positive results, the current study (VITAL; NCT02312206) is a randomized, double-blind, placebo-controlled, phase III trial of NEOD001 in patients with AL amyloidosis and cardiac dysfunction. Methods: Eligible patients with a diagnosis of AL amyloidosis (newly diagnosed and treatment naive) with cardiac dysfunction (N-terminal pro-brain natriuretic peptide [NT-proBNP] 650-8500 pg/mL) will be randomly assigned to receive NEOD001 (24 mg/kg q28d) or placebo. Concurrent anti-plasma cell therapy will be allowed in both arms. The primary end point is a composite evidence-based measure consisting of all-cause mortality or cardiac hospitalization. Secondary end points include NT-proBNP response, time to cardiac mortality or cardiac hospitalization, change in the 6-minute walk test, change in the Short Form-36 (SF-36) Questionnaire and Kansas City Cardiomyopathy Questionnaire (KCCQ), and renal and hepatic response. The study has 90% power to detect a ≥ 30% difference in events between treatment groups. An interim analysis for efficacy or futility is planned. Estimated enrollment is 236 patients. The VITAL phase III trial has commenced. Clinical trial information: NCT02312206.
Rescue of B Cells Development in an Animal Model of X-Linked Agammaglobulinemia(XLA) Via B Lineage-Specific Lentiviral Gene Therapy.
Authors: S. Humblet-Baron, W. Zhang, K. Kipp, S. Khim, J. Jarjour, K. Sommer, D.J. Rawlings
Journal: Blood (2005)
SP0070 How To Treat IGG4-Related Disease
Authors: J.H. Stone
Journal: Annals of the Rheumatic Diseases (2016)

IgG4-related disease (IgG4-RD) is an emerging condition highly relevant to rheumatologists because of its immune-mediated nature, its propensity to cause multi-organ disease, and its ability to mimic multiple classic rheumatologic conditions. IgG4-RD readily mimics Sjogren9s syndrome, lupus nephritis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, sarcoidosis, large-vessel vasculitis (e.g., giant cell arteritis) and others. Despite its only recent recognition approximately a dozen years ago, we have learned much about the pathophysiology of this condition. Our understanding of disease mechanisms informs both current and future approaches to treatment. I will discuss the practical, hands-on management of IgG4-RD and also consider ways in which our mechanistic understanding is driving current treatment trials. <h3>Disclosure of Interest</h3> J. Stone Grant/research support from: Roche, Genentech, Xencor, Consultant for: Roche, Genentech, Xencor
THU0293 Safety, Pharmacokinetics, Enzyme Activity, and Immunogenicity of RSLV-132, A Novel Rnase Fusion Protein Developed To Reduce RNA-Containing Immune Complexes in Systemic Lupus Erythematosus
Authors: D. Burge, J. Doedens, J. Eisenman, K. Elkon, C. Gabel, J. Posada
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> RNA-associated with immune complexes (ICs) is recognized to play a central role in driving interferon production and systemic inflammation in systemic lupus erythematosus (SLE). To date, therapeutic strategies which have sought to block interferon directly or to target various B-cell regulatory proteins have met with mixed success. Given the proximal point of nucleic acid-containing ICs in the inflammatory cascade, reduction in associated RNA is expected to render the ICs less pathogenic. RSLV-132 is a fully-human Fc fusion protein consisting of the Fc domain of IgG1 fused to human RNase 1 that is designed to enzymatically digest RNA-containing ICs. <h3>Objectives</h3> This multiple ascending dose study of RSLV-132 in SLE patients was carried out to assess the safety, pharmacokinetics (PK), serum enzyme activity, and immunogenicity of this novel biologic in SLE. <h3>Methods</h3> A phase 1b, multicenter, randomized, double-blind, placebo-controlled study evaluated 4 dose cohorts (0.3 – 10.0 mg/kg) administered by intravenous infusion. Each cohort consisted of 8 subjects (6 received RSLV-132 and 2 received placebo). Three to five doses were given over 29 days. Serum samples were collected and analyzed for PK analysis, anti-drug antibody (ADA) assessment, autoantibody profiles, and RNase catalytic activity assessment. <h3>Results</h3> A total of 61 adverse events (AEs) were recorded in the 32 subjects during the study. One grade 3 event (cholecystitis; unrelated) occurred in a subject in the 0.3 mg/kg group There were no deaths in the study. The PK analysis demonstrated a linear increase in serum RSLV-132 concentration with a terminal half-life of approximately 19 days. None of the subjects in the study were positive for ADA. RNase catalytic activity increased in a proportional manner up to approximately 100 ug/ml at C<sub>max</sub> in the 10 mg/kg dose cohort, and very closely paralleled the drug concentration curve detected by ELISA. SLEDAI scores were recorded during the study and of the evaluable subjects (SLEDAI &gt;0) a greater proportion of RSLV-132-treated subjects (44%) saw a reduction in SLEDAI scores than in the placebo group (33%). Given the small size of the study this trend will need to be confirmed in larger studies. <h3>Conclusions</h3> RSLV-132 is a promising, novel biologic for the treatment of SLE. An excellent safety profile was observed in the current study. The PK profile showed good dose-proportionality and the observed half-life will support bi-weekly dosing going forward. High serum RNase activities were achieved and sustained over the entire course of the study with no evidence of an ADA response. The results of this study support continued development of RSLV-132 in SLE. <h3>Disclosure of Interest</h3> None declared
Reservations About Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations—Reply
Authors: Catherine A. Shu, Malcolm C. Pike, Noah D. Kauff
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Oncology journal