tbuckley/cabot-search huggingface dataset:
SP0231 How to Treat/Manage: Psoriatic Arthritis
Authors: O. FitzGerald
Journal: Annals of the Rheumatic Diseases (2015)

The treatment and management of Psoriatic Arthritis (PsA) is frequently challenging. Late diagnosis, diverse musculoskeletal features including arthritis, enthesitis, dactylitis and axial involvement, extra-skeletal features including psoriasis, nail dystrophic change and uveitis and co-morbidities in particular metabolic syndrome necessitate a comprehensive assessment of each patient when choosing the most appropriate therapy. It is not sufficient simply to adopt outcome measures developed for other conditions such as rheumatoid arthritis and while the field continues to evolve, PsA-specific assessment tools and outcome measures should be employed. In this session, appropriate instruments and outcome measures which can be used in a clinic setting will be reviewed. A new, freely available web-based tool which includes all the appropriate instruments and which calculates both Minimal Disease Activity (MDA) and Composite Psoriatic Disease Activity Index (CPDAI) will be demonstrated. In addition, current treatment guidelines and algorithms will be reviewed including Treat-to-Target guidelines. Finally, with a significant proportion of patients failing to respond adequately to targeted therapy, the presentation will conclude with a look into the future and how developments in genetics and biomarkers might assist in ensuring that our PsA patients receive the most effective and safe medication in the most time-efficient manner. <h3>Disclosure of Interest</h3> O. Fitzgerald Grant/research support from: Abbvie, Pfizer, BMS, Consultant for: Cellgene, Janssen, Speakers bureau: Cellgene, Amgen
RARE-01PROLONGED DISEASE CONTROL WITH MEK INHIBITOR IN NEUROFIBROMATOSIS TYPE I ASSOCIATED GLIOBLASTOMA
Authors: Malaka Ameratunga, Grant McArthur, Lawrence Cher
Journal: Neuro-Oncology (2015)

BACKGROUND: Neurofibromatosis type 1 (NF1), is a common inherited autosomal dominant genetic disorder, and has been associated with glioma. Neurofibromin, encoded by the NF1 gene, downregulates the RAS-MAPK (MEK) pathway. Its loss in NF1 leads to activation of the Ras signalling pathway and has been associated with the development of multiple tumours. Preclinical testing suggests activity of MEK inhibitors in NF-1 associated tumors, but no clinical data is available. We report a case of disease control by a MEK inhibitor in recurrent NF1-associated GBM. METHODS: Case report. RESULTS: A 28 year old male with a past history of NF1 associated optic glioma, presented with a left cerebellar glioblastoma (GBM) in October 2011. The patient underwent subtotal resection, chemoradiotherapy and adjuvant temozolomide initially. He developed recurrence in June 2014 which was resected and complicated by hydrocephalus requiring a ventriculo-peritoneal shunt. He progressed on second-line carboplatin and had re-resection in August 2014. He was trialled on everolimus with stable disease for 2 months. Temozolomide was added in November 2014 and controlled disease until progression in February 2015. He was trialled on a MEK inhibitor (trametinib) and since February 2015 the patient has maintained stable disease on MRI, with reduction in oedema and size of the lesion not meeting RANO response criteria. The patient had developed an acneiform rash, which has been managed with doxycycline but has otherwise tolerated treatment well. He has had some minor clinical improvement and has been able to reduce steroid dose. CONCLUSION: NF1 associated GBM is rare. Preclinical data has suggested abnormal signalling of the RAS-MEK pathway as contributory. Here we describe the first case of substantial clinical benefit at minimal toxicity to a MEK inhibitor in a patient with treatment refractory NF1 associated GBM. This case highlights a potential promising new therapy for NF1 GBM.
Physiologic Frailty in Nonelderly Hematopoietic Cell Transplantation Patients
Authors: Mukta Arora, Can-Lan Sun, Kirsten K. Ness, Jennifer Berano Teh, Jessica Wu, Liton Francisco, Saro H. Armenian, Amy Schad, Golnaz Namdar, Alysia Bosworth, Linus Kuo, Daniel J. Weisdorf, Stephen J. Forman, Smita Bhatia
Journal: JAMA Oncology (2016)

Frailty results in decreased physiological reserve and diminished resistance to stressors; approximately 10% of those in the elderly population (those ≥65 years) are frail. High-intensity treatments and complications after hematopoietic cell transplantation (HCT) injure normal tissues and may increase the risk of frailty even among nongeriatric HCT patients.To determine the prevalence of frailty in young adult HCT patients (18- to 64-year-olds) and siblings; and the impact of frailty on subsequent mortality in HCT survivors.This cohort study, conducted in August 2015 examined 998 HCT survivors, who underwent transplant procedures between 1974 and 1998, who have survived at least 2 years after HCT, and 297 frequency-matched siblings. The study was performed at City of Hope or University of Minnesota with participants completing surveys at home or in the clinic. Hematopoietic cell transplantation survivors and siblings participating in the Bone Marrow Transplant Survivor Study (BMTSS) completed a frailty survey between February 13, 1999 and June 15, 2005 (median time since HCT: 7.9 years); HCT survivors were followed for subsequent mortality (median: 10.3 years from survey).Prevalence and predictors of frailty; impact of frailty on subsequent mortality in HCT survivors. Frailty phenotype defined as exhibiting 3 or more of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The national Death Index, Social Security Death Index and medical records were used for mortality assessment as of December 21, 2011.The 998 HCT survivors were a mean (SD) of 42.5 (11.6) years of age, and the 297 matched siblings were 43.8 (10.9) years of age. The prevalence of frailty among young adult HCT patients exceeded 8%. The HCT survivors were 8.4 times more likely to be frail than their siblings (95% CI, 2.0-34.5; P = .003). Among HCT recipients, allogeneic HCT recipients with chronic graft-vs-host disease (GvHD) were at increased risk of frailty compared with autologous HCT (OR,15.02; 95% CI, 6.6-34.3; P < .001); resolved chronic GvHD (OR, 2.7; 95% CI, 1.1-6.9; P = .04). Cumulative incidence of subsequent all-cause mortality was 39.3% and 14.7% at 10 years for HCT recipients with and without frailty, respectively (P < .001). Frailty was associated with a 2.76-fold (95% CI, 1.7-4.4; P < .001) increased risk of subsequent mortality after adjusting for relevant prognosticators.The prevalence of frailty among young-adult HCT survivors approaches that seen in the elderly general population. Frail HCT survivors are at increased risk of subsequent mortality when compared with nonfrail survivors. This study identifies vulnerable populations needing close monitoring to anticipate and manage morbidity and prevent mortality.
Enzymatic synthesis of DNA.
Journal: JAMA (1963)

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
Acronymic Burlesque in the Shape of Some Pairs
Authors: E.J. H.
Journal: Annals of Internal Medicine (1972)

Editorial Notes1 October 1972Acronymic Burlesque in the Shape of Some PairsE.J. H.E.J. H.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-77-4-653 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe scene is the office of Dr. Nejim, young physician, avid reader of the nation's leading journals of medicine. Mrs. Sniff has just come in.Dr. Nejim: What can I do for you, Mrs. Sniff?Mrs. Sniff: That's what I've come to ask you.Dr. Nejim: Very funny, Mrs. Sniff, but seriously, what is bothering you?Mrs. Sniff: I want you to do something for my cold.Dr. Nejim: COLD? Did you say COLD!!!? You came in at the right time. I have just read an excellent article on surgical treatment of COLD (1), and the outlook is not as...References1. LAFORET E: Surgical management of chronic obstructive lung disease. N Engl J Med 287:175-177, 1972 CrossrefMedlineGoogle Scholar2. KORSCH B and NEGRETE V: Doctor-patient communication. Observations in the pediatric clinic of a large hospital indicate that the physician often talks jargon or seems not to fully heed the patient's concerns. Mutual dissatisfaction is a frequent result. Sci Am 227:66-74, 1972 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: E.J. H. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byASilicon Carbide, SiCR & D in Health Care 1 October 1972Volume 77, Issue 4 Page: 653-653 ePublished: 1 December 2008 Issue Published: 1 October 1972 PDF downloadLoading ...
AB0097 MMP-13 Generates Digestion Fragments of Mimecan, Comp, Matrilin and Col-Ixa. A New Approach to OA Biomarkers Development:
Authors: L. Tío, A. Farran, P. Benito, J. Monfort
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Extracellular matrix degradation is one of the principal features of osteoarthritis (OA). Although several proteases are implicated in this process, MMP-13 presents several properties that lead it as a key point: it is the collagenase that degradates Col-II at a higher rate, and its expression is restricted to embriogenesis, cancer and OA conditions. Biomarkers development has been proposed for the OA diagnoses and progression. However, they have shown lack of specificity. We hypothesized that MMP-13 is able to digest cartilage components of the extracellular matrix others than Col-II. Furthermore, the fragments generated by the digestion are plausible OA-related biomarkers due to the restricted MMP-13 expression. <h3>Objectives</h3> To extract total soluble protein from cartilage obtained from hip OA of patients undertaken to arthroplasty. To digest the protein extract with activated MMP-13 and to explore the fragments generated from different cartilage matrix components previously related with the OA pathofisiology. <h3>Methods</h3> Cartilage samples presenting different degrees of OA development were selected from OA patients after hip replacement. Soluble proteins were extracted with guanidinium chloride method. MMP-13 was activated with APMA and afterward protein digestion was performed at a ratio of 1:100 (MMP:protein) for 16 hours. The digestion pattern of mimecan, asporin, keratocan, COMP, link protein, matrilin and Col-IXa was examined by western-blot. <h3>Results</h3> 20 samples of each cartilage condition (slightly, moderate and severe OA) were included and soluble protein extraction performed. Analysis by Western blot of the digestions showed that asporin, keratocan and Link protein were resistant to MMP-13 degradation. However, mimecan, COMP, matrilin and Col-IXa present detectable MMP-13 digestion products. Fibronectin was degradated but no cleavage fragments were observed. No remarkable differences were observed in the digestion patterns between cartilage from different degrees of development. The sizes of the digestion products observed are summarized in the following table. <h3>Conclusions</h3> COMP, Col-IXa, matrilin and mimecan present detectable fragments generated by MMP-13 and hence these products could represent new OA-related biomarkers. Since MMP-13 is not able to degrade all cartilage extracellular matrix components, synergies with other proteases are guaranteed to the completely cartilage digestion. <h3>References</h3> Ten years in the life of an enzyme: the story of the human MMP-13 (collagenase-3). Tardif G, Reboul P, Pelletier JP, Martel-Pelletier J. Mod Rheumatol. 2004;14(3):197-204. Biomarkers and proteomic analysis of osteoarthritis. Hsueh MF, Önnerfjord P, Kraus VB. Matrix Biol. 2014 Oct;39:56-66. <h3>Disclosure of Interest</h3> None declared
The 131I antiferritin breakthrough.
Authors: C G Moertel
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.4.608 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3958772 The 131I antiferritin breakthrough. C G MoertelxC G MoertelSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.4.608 PDF "The 131I antiferritin breakthrough.." Journal of Clinical Oncology, 4(4), pp. 608–609© 1986 by American Society of Clinical Oncology
The Boškoski-Costamagna ERCP Trainer: from dream to reality
Authors: Ivo Boškoski, Guido Costamagna
Journal: Endoscopy (2016)

We read with interest the article by Jovanovic et al. on the initial validation of a new mechanical endoscopic retrograde cholangiopancreatography (ERCP) training model [1]. Five trainees and five endoscopists, with and without ERCP experience, were involved in the evaluation of the model. The conclusion was that the model is a useful tool for ERCP training, particularly in improving the position of the scope, handling the wheels and the elevator, targeting the papilla, selectively cannulating the biliary and pancreatic ducts, extracting stones, and placing plastic and metal stents.
Lipase Activity during Experimental Epidermal Carcinogenesis&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: S. K. Kung, M. D.
Journal: JNCI Journal of the National Cancer Institute (1949)

Lipase Activity during Experimental Epidermal Carcinogenesis Get access S. K. Kung, M. D. S. K. Kung, M. D. Barnard Free Skin and Cancer Hospital and Washington University School of Medicine, St. Louis, Missouri; Department of Pathology, National Defense Medical Center, Shanghai, China Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 9, Issue 5-6, April-June, Pages 435–438, https://doi.org/10.1093/jnci/9.5-6.435 Published: 01 April 1949 Article history Received: 23 November 1948 Published: 01 April 1949
Low-Dose Interleukin-2 for Treating Postautologous Transplant Cytogenetic Abnormality Recurrency in a Case of Acute Myeloid Leukemia With Hyperdiploidy
Authors: G. De Rosa, L. Pezzullo, C. Selleri, A.M. Raiola, L. Luciano, M. Picardi, B. Rotoli
Journal: Blood (1998)
Alexithymia: an experimental study of cerebral commissurotomy patients and normal control subjects
Authors: W D TenHouten, K D Hoppe, J E Bogen, D O Walter
Journal: American Journal of Psychiatry (1986)

This study assessed alexithymia in six patients with complete cerebral commissurotomy, two patients with partial commissurotomy, and eight matched control subjects. Comparisons were based on content-analytic measures of the subjects' spoken and written responses to a film that symbolically represented death and loss. The commissurotomized patients were more alexithymic on all four lexical-level variables, all six sentential-level variables, and all six global-level variables. Discriminant function analysis found a linear combination of four variables that effectively discriminated groups of fully commissurotomized, partially commissurotomized, and normal control subjects and correctly classified 15 of the 16 subjects.
The NF-κB-Inducing Kinase (NIK) Is Involved in Both Classical and Alternative NF-κB Activation and Is Necessary for the Survival of T Cell Lymphoma Cells,
Authors: Lina Odqvist, Margarita Sánchez-Beato, Esperanza Martín-Sánchez, Juan C Cigudosa, Javier Menarguez Palanca, Federico García Bragado, Purificación Domínguez Franjo, Renato Franco, Miguel A. Piris
Journal: Blood (2011)
SP0171 How to Treat/Manage (Hot) Osteoporosis
Authors: P. Geusens
Journal: Annals of the Rheumatic Diseases (2015)

The etiology of fractures is multifactorial, including factors that increase the risk of bone fragility and the risk of falls. In terms of bone fragility, the final pathway is the degree and balance of bone turnover and the quantity, structural distribution and quality of the remodeled bone. Treating osteoporosis means preventing a first or subsequent fracture in patients who have been identified to be at high risk for fractures. Fracture prevention can be summarized using a 5-step approach (figure). The <i>first</i> step is case finding: which subjects/patients deserve attention for fracture risk evaluation? These include patients with a recent fracture (increasingly evaluated in the context of a Fracture Liaison Service), patients with diseases (e.g. inflammatory rheumatic diseases) or medications (e.g. glucocorticoids) that are known to increase the risk of fractures, and subjects with an accumulation of other risk factors for fracture. The <i>second</i> step is risk evaluation, for which bone densitometry, imaging of the spine and evaluation of the presence of risk factors (as found in the FRAX and Garvan algorithms) are available. Once a patient at high risk for fracture is identified, the <i>third</i> step is differential diagnosis for underlying diseases using medical history, clinical examination and laboratory tests. In the <i>fourth</i> step, medical therapy consists of instructing the patient about life style, fall prevention, ensuring sufficient calcium and vitamin D intake and discussion of the possibilities of medication. The choice of drugs is based on the spectrum of demonstrated fracture prevention (vertebral, non-vertebral and hip fractures), route (oral, SC, IV) and frequency of administration (from daily to yearly two times or once) and safety profile. Anti-resorptive drugs (bisphosphonates, denosumab, SERMs), that decrease high bone turnover, are a major approach for fracture prevention. In patients with severe osteoporosis, or having new fractures despite adequate anti-resorptive drug treatment and in patients with low bone remodeling, such as in glucocorticoid osteoporosis, osteo-anabolic treatment (recombinant human PTH fragment teriparatide) should be considered. The <i>fifth</i> step is follow-up for checking compliance, tolerance and efficiency, and to decide about duration of treatment. Possible new treatment options include odanacatib, a specific inhibitor of cathepsin-K, the main collagenase of the osteoclast, for which the results of a phase III clinical trial are on the way, and anti-sclerostin antibodies that stimulate bone formation and that are studied in phase II-III clinical trials. <h3>Disclosure of Interest</h3> P. Geusens Grant/research support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Roche, UCB, BMS, Novartis, Consultant for: Amgen, Speakers bureau: Pfizer, Abbott, Lilly, Amgen, MSD, Will
Characteristics of NSCLCs harboring <i>NRAS</i> mutations.
Authors: Kadoaki Ohashi, Lecia V. Sequist, Martin Sos, Xi Chen, Charles M. Rudin, Teresa Moran, Maria E. Arcila, Christine Marie Lovly, Cindy L Vnencak-Jones, Hidefumi Sasaki, Dora Dias-Santagata, Steven M. Dubinett, Gregory J. Riely, Marc Ladanyi, Wilbur A. Franklin, Mark G. Kris, D. Ross Camidge, Paul A. Bunn, William Pao
Journal: Journal of Clinical Oncology (2012)

7532 Background: We sought to determine the frequency and clinical characteristics of patients with non-small cell lung cancers (NSCLCs) harboring NRAS mutations. We used preclinical models to identify targeted therapies likely to be of benefit against NRAS mutant lung cancer cells. Methods: We reviewed data in the Catalogue of Somatic Mutations in Cancer (COSMIC) and clinical history from patients with NSCLC whose tumors underwent systematic screening for driver mutations including NRAS. Patient characteristics examined included age, gender, race, smoking history, disease stage, treatment history, and overall survival (OS). 6 NSCLC cell lines with NRAS mutations were screened for sensitivity against multiple targeted agents. Gene expression was profiled using Affymetrix U133A arrays in 5 NRAS mutant NSCLC cell lines, 8 with EGFR mutations and 17 with KRAS mutations. Results: Among 4524 patients with NSCLC tested, NRAS mutations were present in 29 (0.64%). The types of substitutions found were Q61H/K/L/R and G12A/C/D/R/S, with NRAS Q61L the most common (n=14; 48%). One tumor had a concurrent KRAS mutation. 83% had adenocarcinoma histology, with no significant differences in gender. While 90% of patients were former or current smokers, smoking-related G:C&gt;T:A transversions were significantly less frequent in NRAS than in KRAS-mutant NSCLC (KRAS: 66%, NRAS: 13%, p&lt;0.05). Systemic chemotherapy showed limited efficacy in 7 patients with metastatic disease (median OS 7 mos). 5 of 6 NRAS mutant lung cancer cell lines were sensitive to the MEK inhibitors, AZD6244 and GSK1120212, while other targeted agents (against EGFR, ALK, MET, IGF-1R, PIK3CA, BRAF) were minimally effective. Gene expression profiles of NRAS mutant cell lines were distinct from those with KRAS or EGFR mutations. Conclusions: NRAS mutations define a distinct subset of NSCLCs (~1%) with potential sensitivity to MEK inhibitors. While NRAS gene mutations are more common in current/former smokers, the types of mutations are not those classically associated with smoking.