tbuckley/cabot-search huggingface dataset:
Cost effective analysis of ramucirumab and nivolumab in the second-line treatment of metastatic non-small cell lung cancer using open claim dataset.
Authors: Yi Wang, Jiaqiang Qin, Haoxuan Yan, Ruth Anne Phillips
Journal: Journal of Clinical Oncology (2016)

e18282 Background: Confronting the challenge of improving Non Small Cell Lung Cell (NSCLC) survival, both ramucirumab and nivolumab were approved by the FDA as second line treatment of metastatic NSCLC in 2014. However, the price of these expensive medications should be assessed to avoid a delay of benefits to the diseased population. This study aims to evaluate the cost effectiveness of these two new drugs to optimize NSCLC treatment. Methods: Electronic query of CMS-1500 medical claims identified eligible metastatic NSCLC patients that presented to oncology practices of 2654 oncologists in 49 different states. All eligible patients were previously on first line therapy and initiated docetaxel single agent therapy between January 1, 2013 and November 30th, 2015. The monthly charge of a patient after entering ramucirumab+docetaxel or nivolumab single agent regimen was compared with the charge before the new regimen. Incremental Cost-Effectiveness Ratios (ICERs) were calculated using the difference in monthly charge to the payer and incremental benefits derived from survival data in Phase III trials. Results: Of the 5546 patients who initiated docetaxel single agent regimen, 77 were switched to ramucirumab. 416 were switched to nivolumab. The mean monthly charge to payer was $5653.69 (5546.06, 5761.317) for docetaxel single agent regimen, $19042.75 (18584.95, 19500.55) for ramucirumab+ docetaxel and $22810.13 (22460.69, 23159.58) for nivolumab single regimen. ICER was $12060.12 (10477.74, 15197.94) per quality adjusted life year (QALY) for ramucirumab and $7151.86 (7024.23, 8357.89) QALY for nivolumab. No significant difference in overall cost of second-line regimens was observed within the study period. The results were robust to all parameters tested in sensitivity analysis Conclusions: Nivolumab is a more cost effective second line treatment compared to ramucirumab.
The value of <sup>18</sup>F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study
Authors: Verena Schönau, Kristin Vogel, Matthias Englbrecht, Jochen Wacker, Daniela Schmidt, Bernhard Manger, Torsten Kuwert, Georg Schett
Journal: Annals of the Rheumatic Diseases (2017)

Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions. Diagnosis of underlying disease may be improved by 18F-fluorodesoxyglucose positron emission tomography (18F-FDG-PET).Prospective study to test diagnostic utility of 18F-FDG-PET/CT in a large cohort of patients with FUO or IUO and to define parameters that increase the likelihood of diagnostic 18F-FDG-PET/CT. Patients with FUO or IUO received 18F-FDG-PET/CT scanning in addition to standard diagnostic work-up. 18F-FDG-PET/CT results were classified as helpful or non-helpful in establishing final diagnosis. Binary logistic regression was used to identify clinical parameters associated with a diagnostic 18F-FDG-PET/CT.240 patients were enrolled, 72 with FUO, 142 with IUO and 26 had FUO or IUO previously (exFUO/IUO). Diagnosis was established in 190 patients (79.2%). The leading diagnoses were adult-onset Still's disease (15.3%) in the FUO group, large vessel vasculitis (21.1%) and polymyalgia rheumatica (18.3%) in the IUO group and IgG4-related disease (15.4%) in the exFUO/IUO group. In 136 patients (56.7% of all patients and 71.6% of patients with a diagnosis), 18F-FDG-PET/CT was positive and helpful in finding the diagnosis. Predictive markers for a diagnostic 18F-FDG-PET/CT were age over 50 years (p=0.019), C-reactive protein (CRP) level over 30 mg/L (p=0.002) and absence of fever (p=0.001).18F-FDG-PET/CT scanning is helpful in ascertaining the correct diagnosis in more than 50% of the cases presenting with FUO and IUO. Absence of intermittent fever, higher age and elevated CRP level increase the likelihood for a diagnostic 18F-FDG-PET/CT.
The Difficult Transition
Authors: Marni B. Siegel
Journal: JAMA Oncology (2017)

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
ACR–ACNM Practice Parameter for the Performance of Dopamine Transporter (DaT) Single Photon Emission Computed Tomography (SPECT) Imaging for Movement Disorders
Authors: Rathan M. Subramaniam, Kirk A. Frey, Christopher H. Hunt, Gustavo A. Mercier, Lilja B. Solnes, Patrick M. Colletti, Yang Lu, Bital Savir-Baruch, Hadyn T. Williams
Journal: Clinical Nuclear Medicine (2017)

This American College of Radiology and American College of Nuclear Medicine joint clinical practice parameter is for performance of dopamine transporter single photon emission computed tomography (SPECT) imaging, for patients with movement disorders. Parkinsonian syndrome (PS) consists of a group of neurodegenerative diseases including Parkinson disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and dementia with Lewy bodies (DLB). Accurate diagnosis of PS is critical for clinical management. An important diagnostic dilemma is the differentiation of PS and non-neurodegenerative disorders, such as essential tremor (ET) or drug-induced tremor, due to the overlap of clinical symptoms. The management approach to these conditions is distinctly different. An abnormal iodine-123 ioflupane SPECT scan suggests a decreased amount of dopamine transporter in the striatum, that is, a diagnosis of nigrostriatal neurodegenerative PS, whereas a normal scan suggests ET or other nondegenerative parkinsonism (drug-induced, vascular, or psychogenic).
Prognostic and therapeutic impact of cytogenetic abnormalities in patients with myelodysplastic/myeloproliferative neoplasms, unclassifiable.
Authors: Abhishek Avinash Mangaonkar, Hassan Alkhateeb, Aref Al-Kali, Naseema Gangat, Kebede Begna, Michelle A. Elliott, William J. Hogan, Darci Zblewski, Rhett P. Ketterling, Rebecca L. King, Mark Robert Litzow, Ayalew Tefferi, Mrinal Mahesh Patnaik
Journal: Journal of Clinical Oncology (2017)

7058 Background: The 2016 WHO classification includes myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U), as an MDS/MPN overlap syndrome not meeting criteria for well-defined entities such as CMML. No standard prognostication or treatment guidelines exist for such patients. Methods: We retrospectively identified MDS/MPN-U cases from 1990-2016 through our myeloid malignancies database. All bone marrow reports were reviewed to ensure compliance with 2016 WHO criteria. Clinical &amp; cytogenetic parameters at diagnosis were assessed &amp; compared with treatment outcomes. Results: Eighty nine patients met study criteria, with a median age of 69 years (range: 37-93); 58 (65%) males. Median follow-up was 22.2 months (range: 0-172), with 41 (46%) deaths &amp; 13 (15%) leukemic transformations. Median OS was 24.8 months (range: 0-172). 43 (53%) patients had an abnormal karyotype, with common abnormalities being trisomy 8 (12%), complex karyotype (9%) &amp; del (20q) (6%). Given the fewer types of abnormalities identified, the IPSS cytogenetic stratification was more effective than IPSS-R, with risk categorization including; 45 good (55%), 20 intermediate (25%) &amp; 16 high risk (20%) respectively (8 unavailable). On univariate analysis, increased age (p = 0.05), decreased hemoglobin (p = 0.02), higher ANC (p = 0.03), circulating immature myeloid cells (p = 0.02), higher LDH (p = 0.009), absence of bone marrow ring sideroblasts (p = 0.001) &amp; higher risk (intermediate &amp; high) IPSS cytogenetic categories (p = 0.01) adversely impacted OS. In a multivariate model that included the aforementioned variables, higher risk IPSS cytogenetics retained a negative prognostic impact (p = 0.04). 28 patients received a median of 6 cycles (range: 1-21) of hypomethylating agent therapy (HMA), with an overall response rate of 18% (CR-3, PR-2). All responders had an abnormal karyotype (p = 0.01). However, HMA did not affect either OS or LFS. Conclusions: Intermediate &amp; high risk IPSS cytogenetic categories independently &amp; adversely impact survival in WHO defined MDS/MPN-U patients. HMA use did not impact OS; however, patients with abnormal karyotypes were more likely to respond.
SP0192 Principles of non-pharmacological management of rheumatic diseases
Authors: T Vliet Vlieland
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background and aims</h3> Rheumatic and musculoskeletal diseases (RMDs) have a major impact on patients9 lives. Apart from symptoms such as pain, stiffness and fatigue, many patients may experience limitations in daily activities and participation in society. Rheumatology health professionals (HPs) play a pivotal role in the improvement and maintenance of patients9 functioning, a crucial aspect of patients9 quality of life. To ensure the quality of care, HPs need to be appropriately trained. For this purpose, one module of the EULAR online course for HPs is dedicated to HPs9 interventions related to various RMDs. <h3>Methods</h3> Using the same methodology, expertise and technology used in other EULAR online courses, the following components of the module were developed: A Main Text, Interactive Clinical Cases, Indepth Discussions and two Assessment sets. <h3>Results</h3> First, 4 learning aims were formulated: After completing the module, the student a. Has an overview of interventions commonly provided by HPs in the treatment of patients with RMDs; b. Demonstrates appropriate understanding of opportunities and limitations of the various interventions employed by HPs on the individual patient level; c. Can properly advise and support patients regarding self-management strategies including e.g., appropriate medication usage, exercises, the application of joint protection and energy conservation, the usage of orthoses and adaptive equipment or other; and d. Can make a substantiated decision on when to refer a patient to another health professional, a physician or a multidisciplinary team. Second, a wide range of modalities, such as exercise therapy, self-management support, cognitive behavioural therapy, the provision of orthoses, assistive devices or physical modalities were described. These were further applied and/or explained by means of Interactive Clinical Cases and Indepth Discussions (Patient education and Physical Activity Interventions). <h3>Conclusions</h3> A module of the EULAR Online course for HPs specifically describes and explains HPs9 interventions employed in the management of people with various RMDs. Its contents will be updated according to new clinical and scientific insights. Moreover, it will be adapted to the educational needs of HPs, by taking into account the comments of the students and perspectives from HPs across Europe. <h3>Disclosure of Interest</h3> None declared
Effectiveness of ravidasvir plus sofosbuvir in interferon-naïve and treated patients with chronic hepatitis C genotype-4
Authors: Gamal Esmat, Tamer Elbaz, Maissa El Raziky, Asmaa Gomaa, Mahmoud Abouelkhair, Hadeel Gamal El Deen, Aliaa Sabry, Mohamed Ashour, Naglaa Allam, Mohamed Abdel-Hamid, Ola Nada, Sherine Helmy, Hanaa Abdel-Maguid, Richard Colonno, Nathaniel Brown, Eric Ruby, Pamela Vig, Imam Waked
Journal: Journal of Hepatology (2017)
OP0299 Serum and glomerular expression of IL32 in lupus nephritis
Authors: S Truglia, C Alessandri, F Ciccia, A Rizzo, T Colasanti, F Miranda, FR Spinelli, F Ceccarelli, G Triolo, A Capozzi, M Sorice, G Valesini, F Conti
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Lupus nephritis (LN) is one of the most severe features of systemic lupus erythematosus (SLE). Several cytokines and chemokines are secreted locally in case of glomerular inflammation. Interleukin 32 (IL32) is a newly described cytokine that exhibits several properties typical of proinflammatory cytokines. <i>Ex vivo</i> and <i>in vitro</i> studies supported the role of Toll like receptors (TLRs) in LN pathogenesis and recent investigations demonstrated that Poly I:C, a ligand for (TLR) 3, strongly induced IL32 production from several cell populations. <h3>Objectives</h3> To investigate serum and urinary levels of IL32 in a cohort of LN patients compared to SLE patients without renal involvement and healthy controls (HC). In addition, we investigated kidney expression of IL32 and <i>in vitro</i> ability of LN patients9 serum IgG to stimulate IL32 production by TLR3 activation in human embryonic kidney 293 cells line stably transfected with a TLR3 plasmid (Hek293/T3). <h3>Methods</h3> Serum and urinary IL32 concentrations were measured using ELISA; a polyclonal rabbit anti-human IL32 was used to evaluate the expression of IL32 in renal biopsies. To assess the production of IL32 induced by patients9 IgG and the transduction pathway of TLR3 we performed Western Blot analysis for IL32, TBK1 and NFkB. <h3>Results</h3> We recruited 60 LN patients, 50 SLE patients without renal involvement and 30 HC; 40 LN patients had an active disease (a-LN) and the remaining 20 were in remission (r-LN). IL32 serum levels were significantly higher in patients with r-LN (median 1368, IQR 3910) and HC (median 721, IQR 2271) compared to SLE patients without renal involvement (median 203, IQR 662.8 pg/ml) (p=0.03 and p=0.018, respectively). There were no significant differences in urinary IL32 levels among LN patients, SLE patients without renal involvement and HC. In LN patients a direct association between IL32 serum levels and disease duration (p=0.02; r 0.2978) was observed. Immuno-histochemical analysis performed on renal biopsies of 20 a-LN and 8 HC showed that IL32 was strongly expressed in renal samples of LN patients, especially in patients with class IV, compared to controls. Western Blot analysis showed that antibodies isolated from LN patients induced <i>in vitro</i> production of IL32 in Hek293/T3 cells as well as the phosphorylation of NFkB and TBK1. <h3>Conclusions</h3> The results of the present study show increased IL32 serum levels in r-LN patients as well as increased expression of such cytokine in renal tissues of a-LN patients. IL32 renal expression and its production by Hek293/T3 cells after patients9 IgG stimulation, probably mediated by TLR3, may suggest the production of IL32 directly at renal level in course of LN. <h3>Disclosure of Interest</h3> None declared
SAT0766-HPR The factors affecting functional abilities in patients with juvenile idiopathic arthritis
Authors: E Tarakci, N Arman, O Kasapcopur
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in pediatric population and is characterized by a heterogeneous group of diseases that include chronic arthritis of unknown origin, which begins before 16 years of age (1). Patients with JIA commonly experience acute and chronic pain, decreased mobility, and joint stiffness leading to restrictions on functional ability and isolation from their peers (2). <h3>Objectives</h3> The aim of this study was to assess relationship between clinical features and functional ability and determine the factors affecting functional abilities in patients with JIA. <h3>Methods</h3> 172 (aged 5–18 years) with JIA were included in this study. Socio-demographic data, clinical features (duration of disease, subtype of JIA, and number of involved joint) and functional ability were assessed with Childhood Health Assessment Questionnaire (CHAQ). Pain and overall well-being were measured using a Visual Analog Scale (VAS). Relations between the factors affecting functional abilities in JIA were assessed by multiple linear regression analysis <h3>Results</h3> The mean age was 10.71±3.47 and the mean disease duration was 5.41±3.53 years. Score of CHAQ was affected by number of involved joint (β=0.18, p&lt;0.05), subtypes of JIA (β=- 2.75, p&lt;0.01) and pain (β=0.15, p&lt;0.05), but were not affected by age (β=-0.03, p&gt;0.05), gender (β=-0.03, p&gt;0.05) and disease duration (β=0.03, p&gt;0.05). In addition to, significant difference was found between all CHAQ subscores (except of "walking") of polyarticular and oligoarticular JIA (p&lt;0.001). Functional abilities of patients with polyarticular JIA were lower than functional abilities of patients with oligoarticular JIA. <h3>Conclusions</h3> In the literature, it reported that functional activities were adversely affected in patients with JIA, when they compared with healthy subjects. In our study, we found that functional abilities were affected by subtypes of JIA, number of involved joint, and pain. But, these were not affected by age, gender, and disease duration in JIA. We suggest that subtypes of JIA, number of involved joint, and pain should be considered, when patients with JIA are directed to physical therapy program to encourage functional abilities. <h3>References</h3> Prakken B, Albani S, Martini A (2011) Juvenile idiopathic arthritis. Lancet 377:2138–2149. Tarakci, E., Yeldan, I., Mutlu, E. K., Baydogan, S. N., &amp; Kasapcopur, O. (2011). The relationship between physical activity level, anxiety, depression, and functional ability in children and adolescents with juvenile idiopathic arthritis. Clinical rheumatology, 30(11), 1415. <h3>Disclosure of Interest</h3> None declared
Antimicrobial Peptide Combined with BMP2-Modified Mesenchymal Stem Cells Promotes Calvarial Repair in an Osteolytic Model
Authors: Zunpeng Liu, Xue Yuan, Min Liu, Gabriela Fernandes, Yejia Zhang, Shuting Yang, Ciprian N. Ionita, Shuying Yang
Journal: Molecular Therapy (2017)

Repair and regeneration of inflammation-induced bone loss remains a clinical challenge. LL37, an antimicrobial peptide, plays critical roles in cell migration, cytokine production, apoptosis, and angiogenesis. Migration of stem cells to the affected site and promotion of vascularization are essential for tissue engineering therapy, including bone regeneration. However, it is largely unknown whether LL37 affects mesenchymal stem cell (MSC) behavior and bone morphogenetic protein 2 (BMP2)-mediated bone repair during the bone pathologic remodeling process. By performing in vitro and in vivo studies with MSCs and a lipopolysaccharide (LPS)-induced mouse calvarial osteolytic bone defect model, we found that LL37 significantly promotes cell differentiation, migration, and proliferation in both unmodified MSCs and BMP2 gene-modified MSCs. Additionally, LL37 inhibited LPS-induced osteoclast formation and bacterial activity in vitro. Furthermore, the combination of LL37 and BMP2 markedly promoted MSC-mediated angiogenesis and bone repair and regeneration in LPS-induced osteolytic defects in mouse calvaria. These findings demonstrate for the first time that LL37 can be a potential candidate drug for promoting osteogenesis and for inhibiting bacterial growth and osteoclastogenesis, and that the combination of BMP2 and LL37 is ideal for MSC-mediated bone regeneration, especially for inflammation-induced bone loss. Repair and regeneration of inflammation-induced bone loss remains a clinical challenge. LL37, an antimicrobial peptide, plays critical roles in cell migration, cytokine production, apoptosis, and angiogenesis. Migration of stem cells to the affected site and promotion of vascularization are essential for tissue engineering therapy, including bone regeneration. However, it is largely unknown whether LL37 affects mesenchymal stem cell (MSC) behavior and bone morphogenetic protein 2 (BMP2)-mediated bone repair during the bone pathologic remodeling process. By performing in vitro and in vivo studies with MSCs and a lipopolysaccharide (LPS)-induced mouse calvarial osteolytic bone defect model, we found that LL37 significantly promotes cell differentiation, migration, and proliferation in both unmodified MSCs and BMP2 gene-modified MSCs. Additionally, LL37 inhibited LPS-induced osteoclast formation and bacterial activity in vitro. Furthermore, the combination of LL37 and BMP2 markedly promoted MSC-mediated angiogenesis and bone repair and regeneration in LPS-induced osteolytic defects in mouse calvaria. These findings demonstrate for the first time that LL37 can be a potential candidate drug for promoting osteogenesis and for inhibiting bacterial growth and osteoclastogenesis, and that the combination of BMP2 and LL37 is ideal for MSC-mediated bone regeneration, especially for inflammation-induced bone loss.
SAT0320 SSC- IGG effects are mediated through distinct pathways in THP-1 cells
Authors: G Eleftheriadis, M Wannick, C Sadik, G Riemekasten
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Peripheral blood mononuclear cells (PBMCs) are thought to play a key role in the pathogenesis and progress of systemic scleroderma (SSc) with patients displaying distinct shifts in count, receptor expression profile and cytokine secretion patterns. SSc-IgG with elevated anti-AT<sub>1</sub>R (angiotensin II type 1 receptor)/ET<sub>A</sub>R (endothelin-1 type A receptor) -AAb (autoantibody) titers have been correlated to disease severity and progression<sup>1</sup>. It remains poorly understood through which pathways SSc- IgG mediates its effects. <h3>Objectives</h3> In this study we sought to analyze the expression patterns of THP-1 cells (a monocytic cell line) after SSc-IgG application and their reversibility through application of numerous pharmacological inhibitors. <h3>Methods</h3> Transcription of IL-8- and CCL-18 in THP-1-cells after SSc-IgG and normal IgG stimulation was quantified by qPCR. Stimulations of THP-1 cells with total IgG of phenotypically different groups of SSc patients as well as ET-1 and AT-2 were carried out. In addition, stimulation with pharmacological inhibitors was conducted in a dose-dependent-manner. The results were quantified by IL-8- and CCL18-ELISA of the supernatants. <h3>Results</h3> Expression of IL-8 and CCL-18 is induced by SSc-IgG treatment in comparison to normal IgG which does not follow this trend. IL-8 secretion of THP-1 cells upon SSc-IgG stimulation is mediated through specific autoantibody effects and transduced through NF-κB, ERK-, and AP-1 pathways. CCL-18 secretion of THP-1 cells upon SSc-IgG stimulation is not mediated through aforementioned pathways. <h3>Conclusions</h3> A stable cell culture system able to reproduce previous PBMC data on IL-8 and CCL-18 induction upon SSc-IgG-treatment could be established and insight was gained regarding key pathways which are involved in the transduction leading to IL-8 secretion. The effects of specific surface receptor expression profiles on transduction remain to be elucidated. <h3>References</h3> Günther, J., Rademacher, J., van Laar, J.M. et al. Semin Immunopathol (2015) 37: 529. <h3>Disclosure of Interest</h3> None declared