tbuckley/cabot-search huggingface dataset:
SP0177 New approaches by targeting soluble mediators
Authors: CP Denton
Journal: Annals of the Rheumatic Diseases (2017)

Although the aetiopathogenesis of systemic sclerosis (SSc) remains incompletely understood there is now sufficient knowledge about the pathobiology of the disease and mechanisms underlying development of fibrosis, autoimmunity and vasculopathy to permit informed selection of candidate soluble mediators that may be important drivers of the disease. This has permitted testing of potential targeting approaches in preclinical models and in vitro tissue culture systems. The data from these studies has informed understanding of the disease and has started to be translated into clinical trials that test hypotheses in vivo in patients. This approach has in turn fueled the concepts of reverse translation that are being applied to further understand SSc mechanisms in model systems and observational cohort studies. Soluble mediators that have emerged as strong targets for therapeutic intervention include TGFbeta superfamily members, connective tissue growth factor, IL13, IL4 and IL6. Studies of agents that target these proteins have been proposed or undertaken. Targeting TGF-beta appears to have benefit for skin thickening and attenuate some of the characteristic TGF-beta regulated genes and proteins in skin. However, the most encouraging data have emerged from targeting the IL6 axis using anti-IL6R neutralizing antibodies. This approach was promising in a Phase II study and further trials are ongoing. Interestingly this approach appears to attenuate macrophage gene expression signatures in the skin, may prevent worsening of lung fibrosis and showed significant benefit in the skin by biomarker analysis and a strong trend of benefit over 48 weeks for skin sclerosis score. Other small clinical trials testing TNF-alpha blockade have been more disappointing. Finally, it is possible that soluble mediators may be identified that directly attenuate the fibroproliferative mechanism of SSc. Experimental studies have suggested that increasing alpha-MSH may have benefit for skin fibrosis in a small controlled clinical trial. Clinical trial design is critical to the success and interpretation of studies targeting soluble mediators to define target engagement, mechanism of action, and possible clinical benefit. Advances in trial design are facilitating progress and it seems likely that, as in other rheumatic diseases, targeting key soluble mediators will become a therapeutic reality of the next few years. Defining the place of such approaches compared to other emerging treatment strategies will remain challenging. <h3>Disclosure of Interest</h3> C. Denton Grant/research support from: Inventiva, CSL Behring, GSK, Bayer, Consultant for: GSK, Actelion, Inventiva, Roche
Outcomes and Risks of Allogeneic Hematopoietic Stem Cell Transplant for Hematological Malignancies in Patients with HIV Infection
Authors: Shukaib Arslan, Nathan W. Cummins, Stacey A. Rizza, Andrew D. Badley, Mark R. Litzow, Willis H. Navarro, Shahrukh K. Hashmi
Journal: Blood (2017)
Proof of concept clinical study by US-guided intratumor injection of VCN-01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer
Authors: M. Hidalgo, M. Bazan-Peregrino, B. Laquente, R Alvarez Gallego, A. Mato-Berciano, M. Giménez-Alejandre, V. Maliandi, M C Riesco Martinez, R. Moreno, M. Morell, M. Perez-Carreras, J. Gornals, S. Prados, G. Capella, R. Alemany, R. Salazar, E. Blasi, C. Blasco, M. Cascallo, R. Garcia-Carbonero
Journal: Annals of Oncology (2019)
Studies Making Use of the Same Randomized Clinical Trial Cohorts—Reply
Authors: Brendan Smyth
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Comparison 18F-FDG-PET/CT criteria for prediction of therapy response and clinical outcome in patients with metastatic melanoma treated with ipilimumab and PD-1 inhibitors
Authors: S. Vari, A. Annovazzi, D. Giannarelli, R. Pasqualoni, R. Sciuto, S. Carpano, V. Ferraresi, F. Cognetti
Journal: Annals of Oncology (2019)
Can the Practice of Retainer Medicine Improve Primary Care?
Authors: James Webster
Journal: Annals of Internal Medicine (2012)

Letters6 March 2012Can the Practice of Retainer Medicine Improve Primary Care?James Webster, MD, MSJames Webster, MD, MSFrom Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-156-5-201203060-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Retainer or concierge practices, as discussed by Huddle and Centor in their article (1), make a commercial contract with selected affluent patients who pay a fee, covering future services. The primary goal of this endeavor, no matter how it is presented, is revenue enhancement for the proprietors. Physicians involved with these practices breach their pact with society. They clearly violate, reject, and disregard the faith and implied contractual duties arising from the large federal and state subsidies that generously supported their undergraduate and postgraduate medical education. They should repay those dollars or, if they choose not to, ...References1. Huddle TS, Centor RM. Retainer medicine: an ethically legitimate form of practice that can improve primary care. Ann Intern Med. 2011;155:633-5. [PMID: 22041952] LinkGoogle Scholar2. Lo B. Retainer medicine: why not for all? [Editorial]. Ann Intern Med. 2011;155:641-2. [PMID: 22041955] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: James Webster, MD, MSAffiliations: From Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoRetainer Medicine: An Ethically Legitimate Form of Practice That Can Improve Primary Care Thomas S. Huddle and Robert M. Centor Retainer Medicine: Why Not for All? Bernard Lo Can the Practice of Retainer Medicine Improve Primary Care? Martin T. Donohoe Can the Practice of Retainer Medicine Improve Primary Care? Thomas S. Huddle and Robert M. Centor Can the Practice of Retainer Medicine Improve Primary Care? Marcy Zwelling Can the Practice of Retainer Medicine Improve Primary Care? Josh J. Umbehr Can the Practice of Retainer Medicine Improve Primary Care? Douglas M. Van Zoeren Metrics 6 March 2012Volume 156, Issue 5Page: 400KeywordsConflicts of interestForecastingHealth disparitiesMedical educationUndergraduates ePublished: 6 March 2012 Issue Published: 6 March 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Refinement of diagnostic criteria and frequency estimation of LPAC syndrome: A French multicenter study
Authors: D. Catherine, C. Bertrand, P.-C. Magali, P. Pascal, C. Yves, N. Béatrice, H. Marie-Pierre, B. Véronique, M. Anware, G. Farid, C. Housset, R. Poupon, Z. David, O. Chazouillères, C. Corpechot
Journal: Journal of Hepatology (2018)
Brexit and medicine shortages: evidence from trade data
Authors: Elizabeth Pisani
Journal: BMJ (2019)

As van Schalkwyk and colleagues note, we have little information about the government’s planning to avoid medicine shortages in the United Kingdom after Brexit.1 The press is already reporting shortages, which some think result from exports to single market partners by distributors profiting from a falling pound.23

HM Revenue and Customs provides data on trade in medical products (https://www.uktradeinfo.com). Figure 1 shows the latest available data for monthly imports and …
Comparison of planning target volume for esophageal cancer target delineation with different ways.
Authors: Qian Shao
Journal: Journal of Clinical Oncology (2012)

e14735 Background: To compare the planning target volume (PTV) of esophageal cancer target delineation with different ways. Methods: There were 15 patients with middle chest esophageal cancer, involving 12 males and 3 females and aged 45-72 years. The median age was 59 years. Positioning in the CT slice thickness of 3mm on the outline of esophageal lesions as GTV.The CTV0 was created by manually contouring the esophagus for 30mm superiorly and inferior to GTV then adding 5mm circumferentially to the created volume to account for microscopic spread. For the PTV0, a 10mm margin in all direction was added to CTV0. The CTV6 was created by manually contouring the esophagus for 24mm superiorly and inferior to GTV then adding 5mm For circumferentially. The PTV6, a 16mm margin in superiorly and inferiorall direction and a 10mm margin in other direction was added to CTV6. The CTV15 was created by manually contouring the esophagus for 15mm superiorly and inferior to GTV then adding 5mm For circumferentially. The PTV15, a 25mm margin in superiorly and inferiorall direction and a 10mm margin in other direction was added to CTV15.The CTV30 was created by manually contouring the esophagus for 0mm superiorly and inferior to GTV then adding 5mm For circumferentially. The PTV30, a 40mm margin in superiorly and inferiorall direction and a 10mm margin in other direction was added to CTV15. Paired t-test using SPSS17.0 to p &lt;0.05 was considered significant difference, compared PTV30, PTV15, PTV6, PTV0 volume. Results: The volumes of PTV30, PTV15, PTV6 and PTV0 showing with the mean ± standard deviation, were 392.51 ± 123.32cm 3 , 366.07 ± 112.78cm 3 , 346.55 ± 103.70cm 3 and 342.36 ± 108.65cm 3 , respectively. The results were significant differences (p ≤ 0.001) except PTV6 vs PTV0. Conclusions: Different ways of esophageal cancer target delineation make significant effects on the PTVs. Choosing the delineation ways of CTV6 or CTV0 are better. It may benefit patients.
Brigatinib in ALK TKI-pretreated ALK+ metastatic non-small cell lung cancer (mNSCLC): The use via expanded access to brigatinib (UVEA-Brig) study
Authors: S. Novello, O.T. Brustugun, J. Cadranel, F. Griesinger, M.J. Hochmair, M. Pérol, S. Popat, N. Bent-Ennakhil, C. Kruhl, E. Felip
Journal: Annals of Oncology (2019)
Obinutuzumab (Gazyva) and High-Dose Methylprednisolone (HDMP) Combination for Patients with Chronic Lymphocytic Leukemia (CLL) - a Phase Ib/II Study
Authors: Januario E Castro, Carlos I. Amaya-Chanaga, Juliana Velez Lujan, Michael Choi, Colin McCarthy, Thomas J. Kipps
Journal: Blood (2017)
HIV, HBV and HCV screening practices in oncology: A cross-sectional interregional survey
Authors: I. Poizot-Martin, M. Taouqi, M. Veyri, S. Brégigeon, M. Pibarot, C. Solas, A. Makinson, A.-G. Marcelin, S. Choquet, J.-P. Spano
Journal: Annals of Oncology (2019)
Assessment of emotional discomfort of oncological patients in the first nursing visit at Donostia University Hospital
Authors: E. Uranga, A. Valverde, M. Salort, M. Otalora, P. Rodriguez, M.J. Esnaola, L. Basterretxea, O. Aizpurua, M. Centeno, L. Moreno, H. Telleria, M.A. Landa
Journal: Annals of Oncology (2019)
Is there any prognostic significance in pleural involvement and/or effusion (Ple-I/E) in patients with ALK-positive NSCLC?
Authors: S. Kilickap, F. Buğdaycı Başal, A. Demirkazik, P. Gursoy, U. Demirci, M. Erman, F. Yumuk, F. Cay Senler, B. Cakar, I. Cicin, A. Ozturk, H.S. Coskun, E. Çubukçu, A. Işıkdoğan, O.F. Olmez, A.M. Tatlı, M. Karaagac, T. Şakalar, Y. Eralp, T. Korkmaz
Journal: Annals of Oncology (2019)
Clinical application of a tissue-engineered airway replacement
Authors: P Macchiarini, P Jungebluth, T Go, Ma Asnaghi, Le Rees, Ta Cogan, A Dodson, S Bellini, J Martorell, Pp Parnigotto, S Dickinson, A Hollander, S. Mantero, Mt Conconi, Ma Birchall
Journal: The Lancet (2008)
Baseline characteristics from CLARINET FORTE: Evaluating lanreotide autogel (LAN) 120 mg every 14 days in patients with progressive pancreatic or midgut neuroendocrine tumours during a standard first-line LAN regimen
Authors: P. Ruszniewski, J. Ćwikła, C. Lombard-Bohas, I. Borbath, T. Shah, U.-F. Pape, X.-M. Truong Thanh, A. Houchard, M.E. Pavel
Journal: Annals of Oncology (2019)
Serum exosomal microRNA-199b-5p as a novel circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer
Authors: D.W. Baek, H.J. Cho, J.H. Baek, S.J. Lee, B.W. Kang, Y.S. Chae, J.G. Kim
Journal: Annals of Oncology (2019)
DNA damage response protects against progressive kidney disease
Authors: Bruce A. Molitoris
Journal: Journal of Clinical Investigation (2019)

The pathophysiology of cellular injury and repair has been extensively studied in acute kidney injury (AKI) for more than 70 years. Although a great deal of knowledge has been generated, a debate over the importance of repairing damaged cells versus replacing them by proliferation remains. In this issue of the JCI, Kishi et al. demonstrate that following kidney epithelial cell injury, DNA repair, rather than cell proliferation, plays the central role in recovery and longevity by minimizing apoptosis, G2/M cell-cycle arrest, and subsequent fibrosis. This has important therapeutic implications and highlights the need for more sensitive techniques to evaluate functional, structural, and molecular recovery following injury.
SP0058 Fine-Mapping Causal Genetic Alleles in Rheumatoid Arthritis and Type I Diabetes
Authors: S. Raychaudhuri
Journal: Annals of the Rheumatic Diseases (2015)

Rheumatoid arthritis and Type I Diabetes are autoimmune disease causing a disabling inflammatory polyarthritis that is the result of complex genetic and environmental factors. Genetic studies have now defined &gt;100 loci for these diseases outside of the major histocompatability complex. Only a handful of these loci implicate coding variation. Because of the difficulty in characterizing non-coding variation, investigators have only in rare instances mapped RA loci to causal alleles. This is a critical bottleneck in linking genetic risk factors to underlying disease mechanisms. If we could define causal alleles it might become possible to identify disease mechanisms, and then we might be better able to target disease therapeutically and to define biomarkers that track with disease activity. Here we first demonstrate that rheumatoid arthritis and type I diabetes risk alleles overlap gene regulatory regions specifically in CD4+ effector and 885 regulatory T cells. We then go on to lay out a fine-mapping strategy based on these results to identify causal variation within 55 Autoimmune disease loci. <h3>Disclosure of Interest</h3> None declared
Phase I evaluation of AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced malignancies
Authors: J. Powderly, A. Spira, R. Gutierrez, D. DiRenzo, A. Udyavar, J.J. Karakunnel, A. Rieger, J. Colabella, D.W. Lai, P. de Souza
Journal: Annals of Oncology (2019)
Prognostic role of the EANO ESMO classification of leptomeningeal metastases
Authors: E. Le Rhun, P. Devos, J. Weller, K. Seystahl, F. Mo, A. Compter, A.S. Berghoff, J. Jongen, F. Wolpert, R. Rudà, D. Brandsma, M. Preusser, M.J. van den Bent, U. Herrlinger, M. Weller
Journal: Annals of Oncology (2019)
Trial in progress: First-in-human study of a novel anti-NY-ESO-1–anti-CD3, TCR-based bispecific (IMCnyeso) as monotherapy in NY-ESO-1/LAGE-1A-positive advanced solid tumours (IMCnyeso-101)
Authors: J. Lopez, R. Shinde, M.A. Burgess, T. Sato, F. Thistlethwaite, B. Van Tine, J.A. Rodon, J. Dukes, R. Easton, S. Marshall
Journal: Annals of Oncology (2019)
New website aims to promote good mental health in England
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Public Health England (PHE) has launched a new campaign aimed at helping people manage and improve their mental health.1

The Every Mind Matters campaign includes a website which provides users with a mental health plan after they answer a five question quiz, as well as advice on improving their own mental health and helping others who may be struggling.

To promote the campaign a commercial television (ITV, Channel 4, and Sky channels) takeover is planned for 7 October at 8 45 pm, when a three minute film written by Richard Curtis and featuring people such as Glenn Close, Freddie Flintoff, and Nadiya Hussain, will be shown simultaneously across the channels.

Speaking at …
A luminal unfolding microneedle injector for oral delivery of macromolecules
Authors: Alex Abramson, Ester Caffarel-Salvador, Vance Soares, Daniel Minahan, Ryan Yu Tian, Xiaoya Lu, David Dellal, Yuan Gao, Soyoung Kim, Jacob Wainer, Joy Collins, Siddartha Tamang, Alison Hayward, Tadayuki Yoshitake, Hsiang-Chieh Lee, James Fujimoto, Johannes Fels, Morten Revsgaard Frederiksen, Ulrik Rahbek, Niclas Roxhed, Robert Langer, Giovanni Traverso
Journal: Nature Medicine (2019)
EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer
Authors: R Le Moigne, C.A. Banuelos, N.R. Mawji, T. Tam, J. Wang, K. Jian, R.J. Andersen, A. Cesano, M.D. Sadar, H.-J. Zhou, P. Virsik
Journal: Annals of Oncology (2019)
Re: Manfred Wirth, Nicola Fossati, Peter Albers, et al. The European Prostate Cancer Centres of Excellence: A Novel Proposal from the European Association of Urology Prostate Cancer Centre Consensus Meeting. Eur Urol 2019;76:179–86
Authors: Yongbao Wei, Ruochen Zhang, Liefu Ye
Journal: European Urology (2019)
Advisory drugs panel is losing independence, says academic who quit
Authors: Jacqui Wise
Journal: BMJ (2019)

A senior member of the independent panel that advises the government on drug related issues has resigned amid what he says is “political vetting” of members.

Alex Stevens, professor in criminal justice at the University of Kent, said that the exclusion of suitably qualified applicants meant that the Advisory Council on the Misuse of Drugs was losing its independence.

In June it emerged that a government minister had vetoed the appointment of Niamh Eastwood, a highly respected lawyer and executive director of the drugs charity Release.1 Victoria Atkins, the minister for crime, safeguarding, and vulnerability, vetoed Eastwood on the basis of tweeted disagreements with government ministers. …
Pathologic response and survival efficacy in patients with initial nodal involvement after neoadjuvant chemotherapy in early breast cancer
Authors: S Morales Murillo, A Gasol Cudos, J Veas Rodriguez, F Vilardell Villellas, D -R Sánchez Guzmán, C Canosa Morales, J Melé Olivé, I. el Koulali, E Iglesias Martínez
Journal: Annals of Oncology (2019)
Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Authors: R. Morales Barrera, I. Matos, M. Gonzalez, C. Suárez, J. Ros, C. Valverde, C. Fernandez, C. Hierro, E. Serra, J. Mateo, S. Gutierrez, J. Martín Liberal, A. Quintana, R. Dienstmann, C. Serrano, E. Garralda, J. Carles
Journal: Annals of Oncology (2019)
Abstract 16761: Initial Arterial pH ≤ 7.05 Predicts Progressively Poor Neurologic Outcomes After Out-of-Hospital Cardiac Arrest: A Propensity-Adjusted Analysis of the C-GRApH Cohort
Authors: Erich L Kiehl, Kyle B Enfield, Lawrence W Gimple, Mark P Adams, Venu Menon
Journal: Circulation (2017)

Background: Lower initial pH after out-of-hospital cardiac arrest (OHCA) has been associated with poor neurologic outcome (NO) and is widely integrated into existing prediction models. While a rece...
The expression of cell cycle regulating proteins and steroid hormone receptor status in invasive breast cancer: association with tumor grade and stage
Authors: Stella Somiari, Albert Kovatich, Jeffrey Hooke, Susan Maskery, Peter Baran, Rick Jordan, Yonghong Zhang, Brenda Deyarmin, Craig Shriver
Journal: Cancer Research (2007)

5216  Using gene expression profiling, breast tumors can be divided into distinct “molecular subtypes” associated with different clinical outcomes. In the clinic, specific immunohistochemical assays are utilized for the determination of treatment options and/or prognosis. However, gene expression profiling and current immunopathological targets still do not provide sufficient information for clinical management of all breast cancer patients. Since transcription factors and their targets are often co-regulated, hierarchical clustering analysis, and/or classification tools examining related set of transcriptional/proliferative proteins might provide patterns associated with tumor stage/grade and subsequently relate to disease prognosis and prediction of response to therapy. The aim of this study was to determine the protein expression “signatures” of two tyrosine kinase receptor family members ERBB1 (EGFR) and ERBB2 along with cyclin D1, c-MYC, Topo II α, p27 and the steroid hormone receptors (ER/PR) that are associated with poor or favorable prognosis. Thirty-six, FFPE breast tumors were analyzed by immunohistochemistry from patient donors between 37-80 years of age. These were stage I (19%), II (47%), III (19%), or IV (15%) breast tumors that were well (28%), moderately (25%) or poorly (47%) differentiated. Forty four percent of the tumors were ER (-) and 56% were ER (+). Fifty-eight percent were PR (-) and 42% PR (+). The phenotypes p27 (-) and EGFR (+) were associated with poorly differentiated tumors (p = 0.001 respectively). Hierarchical clustering algorithms showed poor grade tumors were associated with EGFR (+), ER/PR (-), p27 (-) and cyclin D1 (-). Bayesian networks which, represent probabilistic interactions between the set of variables showed strong interactions between the following; ER/PR, cyclin D1, p27, and tumor grade; ER/PR, p27, EGFR and tumor grade. The Classification & Regression tree node method, which utilizes recursive partitioning to split training records into 2 subsets, was able to split ER (+) tumors based on their PR status and diagnosis (IDCA, ILCA) and ER (-) tumors were split based on diagnosis, p27 and EGFR status. c-MYC expression was significantly different in relation to tumor stage with over expression observed in more advanced stages (p = 0.003). The following expression patterns were observed; ER (+) with high cyclin D1 representing moderate/well differentiated tumors; high Topo II α, EGFR (+), ER/PR (-), and nuclear expression of c-MYC and/or ERBB2 (-) representing poorly differentiated tumors. The association of the observed patterns and their potential role in breast cancer prognosis will be discussed.