tbuckley/cabot-search huggingface dataset:
Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND—A Double-Blind, Randomized, Phase II Study
Authors: Dean A. Fennell, Paul Baas, Paul Taylor, Anna K. Nowak, David Gilligan, Takashi Nakano, Jonathan A. Pachter, David T. Weaver, Arnaud Scherpereel, Nick Pavlakis, Jan P. van Meerbeeck, Susana Cedrés, Luke Nolan, Hedy Kindler, Joachim G.J.V. Aerts
Journal: Journal of Clinical Oncology (2019)

PURPOSE Inhibition of focal adhesion kinase has been shown to selectively kill mesothelioma cells that express low levels of moesin-ezrin-radixin-like protein (merlin). On this basis, we designed a randomized, phase II trial to investigate whether defactinib as maintenance therapy after standard first-line chemotherapy could improve progression-free survival (PFS) in patients with malignant pleural mesothelioma (MPM). METHODS This global, double-blind, randomized, placebo-controlled trial was conducted in patients with advanced MPM and disease control after at least four cycles of first-line chemotherapy. Patients were stratified for merlin and then randomly assigned (in a 1:1 fashion) to receive either oral defactinib or placebo until disease progression, unacceptable toxicity, or withdrawal occurred. The coprimary end points were PFS and overall survival (OS). Quality of life (QoL) was assessed using the Lung Cancer Symptom Scale for Mesothelioma tool. RESULTS Three hundred forty-four patients were randomly assigned to receive either defactinib (n = 173) or placebo (n = 171). The median PFS was 4.1 months (95% CI, 2.9 to 5.6 months) for defactinib versus 4.0 months (95% CI, 2.9 to 4.2 months) for placebo. The median OS was 12.7 months (95% CI, 9.1 to 21 months) for defactinib versus 13.6 months (95% CI, 9.6 to 21.2 months) for placebo (hazard ratio, 1.0; 95% CI, 0.7 to 1.4). Although shorter survival for both defactinib- and placebo-treated patients was observed, in the patients who had merlin-low MPM compared with the patients who had merlin-high MPM, there were no statistical differences in response rate, PFS, OS, or QoL between the treatment groups. The most common grade 3 or worse adverse events were nausea, diarrhea, fatigue, dyspnea, and decreased appetite. CONCLUSION Neither PFS nor OS was improved by defactinib after first-line chemotherapy in patients with merlin-low MPM. Defactinib cannot be recommended as maintenance therapy for advanced MPM.
GATA2 Zinc Finger Mutations Affect DNA-Binding and Promote Granulopoietic Differentiation
Authors: Georg Leubolt, Belay Tizazu, Sayantanee Dutta, Monica Cusan, Theresa Sippenauer, Rouzanna Istvanffy, Robert A.J. Oostendorp, Wolfgang Hiddemann, Philipp A. Greif
Journal: Blood (2018)
P170 Potential role for the chemokine CCL22 in the development and early progression of rheumatoid arthritis
Authors: B Réthi, A Krishnamurthy, A Circiumaru, K Sakurabas, V Joshua, M Sun, C Szu-Ying, M Engström, H Wähämaa, A Hensvold, JE Smith, AI Catrina
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Young investigator. <h3>Introduction</h3> CCL17 and CCL22 are chemokines that bind to the receptor CCR4, which is expressed on various immune cells as well as on neurons. CCL17 has been shown to mediate the pro-inflammatory and algesic actions of GM-CSF in murine arthritis models<sup>1</sup> and CCL22 could activate nociceptive neurons in cell culture<sup>2</sup> or induce hyperthermia by acting on the hypothalamus.<sup>3</sup> Our previous studies have indicated that chemokine production by osteoclasts (OCs) might contribute to bone damage and arthralgia in the presence of anti-citrullinated protein antibodies.<sup>4 5</sup> <h3>Objectives</h3> We analyzed the expression and potential roles of CCL17 and CCL22 during rheumatoid arthritis (RA). <h3>Methods</h3> We compared CCL17 and CCL22 levels in the sera of individuals at risk of developing RA, in patients at early stages of RA and in healthy controls. We also studied the production of these molecules in OC cultures. We analyzed whether CCL22 can induce arthralgia or affect OC development. <h3>Results</h3> Serum levels of CCL22 were elevated in individuals at risk of developing RA and in early untreated RA, when compared to healthy controls. On the contrary, CCL17 levels showed no significant difference between the studied cohorts. In the group of RA patients, higher CCL22 concentrations were associated with smoking. In OC cultures CCL22 production was triggered by M-CSF or GM-CSF and CCL22 levels correlated with both of these cytokines in the synovial fluid of RA patients. CCL22 induced arthralgia when injected into the ankle joints of mice and it stimulated OC differentiation in cell culture. <h3>Conclusions</h3> The early increase of CCL22 might contribute to the development of RA, potentially by inducing pain and osteoclastogenesis. Inflammatory cytokines, like GM-CSF and M-CSF, and also by environmental triggers such as smoking can contribute to the increase of CCL22. <h3>References</h3> Achuthan A, <i>et al. J Clin Invest</i> 2016. Oh SB, <i>et al. J Neurosci</i> 2001. Osborn O, <i>et al. Cytokine</i> 2011. Krishnamurthy A, <i>et al. Ann Rheum Dis</i> 2016. Wigerblad G, <i>et al. Ann Rheum Dis</i> 2016. <h3>Disclosure of Interest</h3> B. Réthi: None declared, A. Krishnamurthy: None declared, A. Circiumaru: None declared, K. Sakurabas: None declared, V. Joshua: None declared, M. Sun: None declared, C. Szu-Ying: None declared, M. Engström: None declared, H. Wähämaa: None declared, A. Hensvold: None declared, J. Smith Employee of: GSK, A. Catrina: None declared.
P037 Anti-carbamylated protein antibodies: are they useful for the diagnosis of rheumatoid arthritis?
Authors: F Ponchel, L Hunt, M van Delft, P Emery, L Trouw
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Resident. <h3>Introduction</h3> The current EULAR-2010 diagnostic criteria for Rheumatoid Arthritis (RA) relies heavily on the presence of auto-antibodies. So far only anti-citrullinated peptide antibody (ACPA) or rheumatoid factor (RF) are accounted for however, novel auto-reactivities have been described notably anti-carbamylated protein (anti-CarP) and anti-oxydized peptide antibodies. <h3>Objectives</h3> To investigate the potential of anti-CarP antibodies for the diagnosis of RA. <h3>Methods</h3> 402 patients were recruited from an early arthritis register (ethically approved) with a diagnosis recorded over 24 months. 95 healthy controls were included. All participants provided written informed consent. An anti-CarP antibody ELISA was performed using carbamylated FCS as target antigen.<sup>1</sup> Results were expressed as aU/mL. Statistical analysis used ROC and AUC analysis established using SPSS V22. <h3>Results</h3> We first determined the 95% CI of the distribution of ELISA results in HCs to define a negative/positive cut-off for the test, established at &gt;250 aU/mL. 195/402 patient were classified as RA at inclusion; 28 developed RA over time while 56 remained undifferentiated arthritis; 83 had non persistent symptoms and 40 other inflammatory joint diseases. Anti-CarP ELISA results were clearly much higher in RA (median 250 [IQR 25–762], p&lt;0.0001) with 49% of patients being positive as well as in the group that progressed to RA (25% positive, 82 [13–235], p=0.001), compared to all other EAC patients together (8% positive, 26 [5–80]) or HC (5% positive, 41 [1–106]). In this particular cohort, anti-CarP had an odd ratio OR=5.55 for predicting RA with a sensitivity SEN=91.5% and positive predictive value PPV=87%, compared to ACPA which had an OR=8.78 (SPE=92%, PPV=92%) and RF with an OR=4.18 (SPE=85%, PPV 84%). Titres were not associated with other variables (age, gender, JC, CRP or DAS). A ROC analysis determined that linear data (aU/mL) for anti-CarP were not better than a positive/negative status at predicting RA. A score counting the number of auto-antibodies (0–1-2–3) had a high predictive value (AUC=0.840, p&lt;0.0001 SEN/SPE of 65%/95% and PPV/NPV of 94%/68%). We then established that a combination of ACPA+antiCarP was superior at predicting RA (OR=25.1 SEN/SPE=43%/98.5%, PPV/NPV=97%/58%) than the ACPA+RF combination (OR=11.9, SEN/SPE=54%/95%, PPV/NPV=94%/62%), although less sensitive. <h3>Conclusions</h3> Although RF is more frequently observed than anti-CarP, it is also less specific for RA. A combination of ACPA+anti CarP may prove more useful at classifying early arthritis patients for RA than an ACPA+RF combination. Future work needs to establish a standardised assay for anti-CarP and replicate this data. <h3>Disclosure of Interest</h3> None declared.
Pharmacologic Intervention for the Treatment and Prevention of Delirium
Authors: Dan G. Blazer
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
A3.7 Comparison of the Effects of Th17 and Th1 Cells on Endothelial Cells and Synoviocytes
Authors: Arnaud Hot, Laura Maggi, Fabien Lavocat, Francesco Annunziato, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Interaction between different types of T-cells and surrounding non-hematopoietic cells is essential for the proper function of the immune system. Here, we focus on the synoviocytes from RA patients and Endothelial Cells (EC) and compare their interaction with Th1 and Th17 cells. <h3>Methods</h3> To assess the interaction of T cells with stromal cells, the effects of Th1 or Th17 cytokines, Th1 or Th17 clone supernatants and coculture of Th clones and stromal cells were analysed. HUVEC (Human Umbilical Vein Endothelial Cells) were used as a model for EC and synoviocytes were isolated from synovium from RA patients. CD4<sup>+</sup> T cells, derived from PBMCs of healthy donors, were used to obtain T-cell clones. CD4<sup>+</sup> T-cell clones were classified on the basis of their ability to produce IFN-γ and/or IL-17. T cell clones were polyclonally stimulated with anti-CD3/CD28. Cytokine expression was assessed with RT-PCR and production in supernatants by ELISA. <h3>Results</h3> As previously described, IL-17A and TNF-α had a synergistic effect for both cells. Moreover, a stronger induction for IL-6 pro- duction was seen for synoviocytes compared to EC (1005 ± 22 pg/ml versus 250 ± 15 ng/ml respectively). Supernatants from inactivated Th1 or Th17 clones had no effect on EC. Regarding synoviocytes, supernatants from inactivated clones induced IL-6 and IL-8 mRNA with a stronger effect for Th17 cells (1000 fold versus 100 fold compared to resting synoviocytes, p = 0.045). While activated Th1 supernatants had a strong effect on EC and increased the expression of IL-6, IL-8, E-selectin, and tissue factor mRNA (98.12, 89 fold respectively, compare to control), Th17 supernatants had no effect. Activated Th1 and Th17 supernatants had the same effect on synoviocytes (254 and 754 fold compared to control). Th1 cells were more potent inducers of IL-6, IL-8 and tissue factor mRNA in EC than Th17 which had no significant effect (5, 12.5, 7.5 fold respectively compared to control). Th17 cells were most effective to stimulate IL-6 and IL-8 mRNA expression in synoviocytes compared to Th1 (100 fold versus 24 for IL-6 mRNA, p = 0.027). Anti-IL-17 antibody reduced IL-6 production from 20.0 ± 4.5 ng/mL to 13.2 ± 3.9 ng/ml (p = 0.032) in synoviocytes cultured with Th17 clones. <h3>Conclusions</h3> While Th1 cells were able to induce inflammatory cytokine expression in EC and synoviocytes, Th17 cells were only active to promote inflammation in inflammatory cells such as synoviocytes. The effect of Th17 cells appears to depend of IL-17 and the type of stromal cells.
Acquired Pili Torti
Authors: J. Brady Evans, Justin G. Hastings, Benjamin H. Kaffenberger
Journal: JAMA Dermatology (2019)

This case report describes a woman with acquired pili torti and a history of Roux-en-Y gastric bypass, alcohol abuse, and malnutrition who was admitted to the hospital for hepatic encephalopathy secondary to nonalcoholic steatohepatitis.
ECG Challenge: May 10, 2016
Authors: Philip Podrid
Journal: Circulation (2016)

ECG Challenge 1906A 70-year-old man with a history of coronary artery disease and an ischemic cardiomyopathy with a left ventricular ejection fraction of 38% presents to the emergency room with complaints of lightheadedness.His medications include a β-blocker, an angiotensin-converting enzyme inhibitor, and Imdur.His pulse is noted to be slow, and a 12-lead ECG is obtained.
Promoting Sensible Parenting Policies
Authors: Rebekah Diamond
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
HIV and AIDS in the European Union, 2011
Authors: G Likatavicius, M Van de Laar
Journal: Eurosurveillance (2012)

In 2011, a total of 28,038 new HIV diagnoses were reported by European Union and European Economic Area countries. The annual rate of HIV diagnoses does not show clear signs of decrease and HIV continues to be concentrated in selected populations such as men who have sex with men and injecting drug users, and a high proportion reported as late presenters. Despite effective and available antiretroviral treatment, the number of AIDS cases increased in a few countries.
Open‐label, investigator‐initiated, single‐site exploratory trial evaluating secukinumab, an anti‐interleukin‐17A monoclonal antibody, for patients with moderate‐to‐severe hidradenitis suppurativa
Authors: L. Prussick, B. Rothstein, D. Joshipura, A. Saraiya, Y. Turkowski, R. Abdat, A. Alomran, P. Zancanaro, C. Kachuk, N. Dumont, A.B. Gottlieb, D. Rosmarin
Journal: British Journal of Dermatology (2019)
Early transmission and case fatality of Ebola virus at the index site of the 2013–16 west African Ebola outbreak: a cross-sectional seroprevalence survey
Authors: Joseph W S Timothy, Yper Hall, Joseph Akoi-Boré, Boubacar Diallo, Thomas R W Tipton, Hilary Bower, Thomas Strecker, Judith R Glynn, Miles W Carroll
Journal: The Lancet Infectious Diseases (2019)

To date, epidemiological studies at the index site of the 2013-16 west African Ebola outbreak in Meliandou, Guinea, have been restricted in their scope. We aimed to determine the occurrence of previously undocumented Ebola virus disease (EVD) cases and infections, and to reconstruct transmission events.
Intermediate hyperglycaemia to predict progression to type 2 diabetes (ELSA-Brasil): an occupational cohort study in Brazil
Authors: Maria Inês Schmidt, Paula A Bracco, John S Yudkin, Isabela M Bensenor, Rosane Härter Griep, Sandhi Maria Barreto, Cristina D Castilhos, Bruce B Duncan
Journal: The Lancet Diabetes & Endocrinology (2019)
Erratum: "Influence of coagulation factor X on in vitro and in vivo gene delivery by adenovirus (Ad) 5, Ad35, and chimeric Ad5/Ad35 vectors" (Molecular Theraphy (2009) 10.1038/mt.2009.152)
Authors: JA Greig, Smk Buckley, SN Waddington, AL Parker, D Bhella, R Pink, AA Rahim, T Morita, SA Nicklin, JH McVey, AH Baker
Journal: Molecular Therapy (2009)
Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP)
Authors: Rafal Dziadziuszko, Egbert F. Smit, Urania Dafni, Juergen Wolf, Bartosz Wasąg, Wojciech Biernat, Stephen P. Finn, Roswitha Kammler, Zoi Tsourti, Manuela Rabaglio, Barbara Ruepp, Heidi Roschitzki-Voser, Rolf A. Stahel, Enriqueta Felip, Solange Peters
Journal: Journal of Thoracic Oncology (2019)

IntroductionMutations in erb-b2 receptor tyrosine kinase 2 (HER2) oncogene are observed in approximately 3% of lung adenocarcinomas or mixed tumors with adenocarcinoma component. Activity of various biologically distinct HER2 inhibitors, including the pan-HER inhibitor afatinib, has been reported in several retrospective trials or small series in advanced pretreated NSCLC with HER2 mutations. We report the first prospective evaluation of afatinib for the treatment of this molecularly defined entity.MethodsNICHE, a single-arm phase II trial using a two-stage Simon's design, explored the potential of afatinib to control disease in pretreated patients with advanced NSCLC harboring HER2 exon 20 mutations. A total of 13 patients entered the trial and were treated with afatinib 40 mg/day until tumor progression or lack of tolerability.ResultsThe first-stage stopping boundary was crossed when five of nine patients did not achieve disease control at 12 weeks. The accrual into the trial was stopped with total 13 patients enrolled, with 7 (53.8%) achieving disease control at 12 weeks. Except for 1 patient with early death, progression was documented for all patients, with median progression-free survival of 15.9 weeks (95% confidence interval: 6.0–35.4), and median overall survival of 56.0 weeks (95% confidence interval: 16.3– upper limit not estimable). The toxicity profile was in the expected range.ConclusionsAfatinib did not show the expected potential for disease control in NSCLC. However, more than half of the patients in the full cohort achieved disease control at 12 weeks.
Dermoscopic Appearance of Amelanotic Volar Melanoma Compared With Volar Angioma
Authors: Konstantinos Liopyris, Cristian Navarrete-Dechent, Silvia E. Mancebo, Klaus J. Busam, Melissa P. Pulitzer, Ashfaq A. Marghoob, Michael A. Marchetti
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Abstract 1282: NCI's Clinical Proteomic Tumor Analysis Consortium
Authors: Robert C. Rivers, Mehdi Mesri, Chris Kinsinger, Emily Boja, Tara Hiltke, Henry Rodriguez
Journal: Cancer Research (2012)

Abstract Mission: The Clinical Proteomic Tumor Analysis Consortium (CPTAC) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of robust, quantitative, proteomic technologies and workflows. Goals: The overarching goal of CPTAC is to improve our ability to diagnose, treat and prevent cancer. To achieve this goal in a scientifically rigorous manner, the National Cancer Institute (NCI) launched CPTAC to systematically identify proteins that derive from alterations in cancer genomes and related biological processes, and provide this data with accompanying assays and protocols to the public. Genomics initiatives such as The Cancer Genome Atlas (TCGA) have characterized and sequenced the genomic alterations from several types of cancer. CPTAC will leverage its analytical outputs by producing a unique continuum that defines the proteins translated from cancer genomes in order to link genotype to proteotype and ultimately to phenotype. Scientific Approach: The structure of CPTAC is designed to facilitate the efficient implementation of a two-step developmental pipeline, Discovery and Verification. The pipeline originates with the CPTAC Resource Center, which will provide a set of high-quality, genomically characterized clinical biospecimens from patients with a single type of cancer. The Discovery Unit of each Proteome Characterization Center (PCC) will use a set of proteomic technologies to comprehensively analyze the protein composition of this set of biospecimens including mapping proteome to genome and detecting and quantifying protein products that correspond to genomic aberrations. All data from the Discovery Units will be shared within the network via the CPTAC Data Center. Based on this aggregate data set, each Discovery Unit will select and prioritize cancer-related proteins for potential use in the verification step. The selected lists of prioritized proteins by the Discovery Units will be consolidated and collectively prioritized. The Verification Unit of each PCC will develop targeted assays against corresponding protein targets as assigned by the verification plan. The Verification Units will then verify the biomarker candidates by performing these assays in clinically relevant cancer biospecimens (provided by the CPTAC Resource Center). Data from these verification studies will be shared via the CPTAC Data Center. These verified proteins will serve as high-value targets to other initiatives involved in clinical qualification studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1282. doi:1538-7445.AM2012-1282