tbuckley/cabot-search huggingface dataset:
First-line (1L) avelumab treatment in patients (pts) with metastatic Merkel cell carcinoma (mMCC): Preliminary data from an ongoing study.
Authors: Sandra P. D'Angelo, Jeffrey Russell, Jessica Cecile Hassel, Celeste Lebbe, Bartosz Chmielowski, Guilherme Rabinowits, Patrick Terheyden, Isaac Brownell, Isabella Zwiener, Marcis Bajars, Meliessa Hennessy, Howard Kaufman
Journal: Journal of Clinical Oncology (2017)

9530 Background: MCC is a rare, aggressive skin cancer. Avelumab is a fully human anti–PD-L1 antibody. In a phase 2 study in pts with distant mMCC who progressed after prior chemotherapy (JAVELIN Merkel 200; NCT02155647), avelumab showed a manageable safety profile and durable responses, including an objective response rate (ORR) of 31.8%, estimated 6-month durable response rate of 29%, and 6-month overall survival rate of 69%. Here, we report preliminary results from a separate cohort of pts with chemotherapy-naïve mMCC enrolled in the same study. Methods: Eligible pts with mMCC and no prior systemic treatment for metastatic disease received avelumab 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 weeks (RECIST v1.1). Adverse events (AEs) were assessed by NCI CTCAE v4.0. Results: As of Dec 30, 2016, 29/112 planned pts had been enrolled. Median age was 75.0 years (range 47–87). Median treatment duration was 8.1 weeks (range 2.0–37.9). Of 16 pts with ≥3 months of follow-up, unconfirmed ORR was 68.8% (95% CI 41.3–89.0) with CR in 18.8%; confirmed ORR was 56.3% (95% CI 29.9–80.2; 1 unconfirmed PR with discontinuation). Of 25 pts with ≥6 weeks of follow-up, unconfirmed ORR was 64.0% (95% CI 42.5–82.0). All responses were ongoing at last follow-up, including in 5/5 pts with ≥6 months of follow-up (potential to confirm responses). 20/29 pts (69.0%) had a treatment-related AE (TRAE), including grade 3–4 TRAE in 5 pts (17.2%). TRAEs led to discontinuation in 5 pts (17.2%): 2 pts with infusion-related reaction, and 1 pt each with elevated AST and ALT, cholangitis, and paraneoplastic syndrome. There were no treatment-related deaths. 21/29 pts (72.4%) remain on treatment. Conclusions: In initial results from a cohort of chemotherapy-naïve pts with mMCC, avelumab was associated with early responses and a manageable safety profile, consistent with findings for second-line or later avelumab treatment in a previous cohort. These results suggest that responses mature to become durable and the use of 1L avelumab may increase the probability of response vs later-line treatment. Enrollment and follow-up in this 1L cohort are ongoing. Clinical trial information: NCT02155647.
SAT0741-HPR Physical performance and gait speed of faller and non-faller elderly people with knee osteoarthritis living in the community
Authors: M Karapinar, A Abit Kocaman, N Kirdi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease in the elderly population. The main signs and clinical symptoms of this disease are pain, edema, stiffness, and articular instability. OA is considered to be an intrinsic risk factor for the occurrence of falls. Falls constitute as one of the major public health concerns. They frequently have a negative impact on the daily life of elderly people and could lead an increase of dependence, fear of new falls, fractures, immobility and death. <h3>Objectives</h3> The purpose of this study was to compare physical performance and gait speed among older people with knee osteoarthritis with and without a history of falls. <h3>Methods</h3> The community-dwelling older people (65 and older) were recruited from different social senior groups and from the Hacettepe University Hospital Geriatric Outpatient Clinic. 102 patients were screened and 62 subjects with unilateral knee OA were evaluated. We used a standardized questionnaire, consisting of sociodemographic datas, cognitive function, and history of falls during the previous year. Thirty one elderly with a history of falls and also 31 without a history of falls were studied. Physical performance was evaluated with Short Physical Performance Test (SPPT). Walking speeds were measured with Six Metre Walk Test. Fear of falling (FOF) was assessed by a question (Do you have fear of falling? yes/no) <h3>Results</h3> There were no differences between faller and non-faller elderly people in terms of age (76±8,4 years) and BMI (30,4±3,1 kg/m<sup>2</sup>). A statistically significant difference was found in terms of walking speeds and short physical performance test (p&lt;0,005, p&lt;0,005). <h3>Conclusions</h3> As a result of this study, it was shown that the elderly people with knee OA and who have history of falls present worse performance in functional mobility and require a longer period of time to walking. <h3>References</h3> Huang MH, Lin YS, Yang RC, Lee CL. A comparison of various therapeutic exercises on the functional status of patients with knee osteoarthritis. Semin Arthritis Rheum 2003; 32: 398–406. Hinman RS, Bennell KL, Metcalf BR, Crossley KM. Balance impairments in individuals with symptomatic knee osteoarthritis: a comparison with matched controls using clinical tests. Rheumatology 2002; 41: 1388–1394. <h3>Disclosure of Interest</h3> None declared
THU0571 The clinical features of 223 behcet's disease patients in japan
Authors: R Saito, K Nishimura, H Mukoyama, Y Nakamura, T Nagamoto, K Akashi, A Onishi, Y Kogata, J Saegusa, A Morinobu, T Yokota
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Behcet9s disease is a systemic vasculitis disease with oral and genital aphthous ulcers, ocular involvements, skin manifestations, arthritis, gastrointestinal manifestations, neurogenic diseases and vascular involvements. Patients with Behcet9s disease are known to distribute along the ancient Silk Road, including Japan. <h3>Objectives</h3> We evaluate the clinical features of Behcet9s disease in Japan. <h3>Methods</h3> We retrospectively investigated 223 patients (108 males and 115 females) who fulfilled the International Criteria for Behcet9s Disease (ICBD) from January, 2006 until May, 2015.We examined sex, onset age, disease type, clinical symptoms, laboratory data and medications. <h3>Results</h3> Median age at diagnosis was 36.0±12.8 years old. Oral ulcers were the most common manifestation (98.2%), followed by genital ulcers (62.4%), ocular involvements (53.2%), erythema nodosum (53.2%), acneiform lesions (51.8%), arthritis (38.6%), gastrointestinal manifestations (25.1%), neurogenic diseases (9.0%), and vascular involvements (8.1%). The relationship of HLA and disease manifestations was studied in 123 patients (41.5% with HLA-B51 and 24.1% with HLA-A26). The frequency of acneiform lesions, ocular involvements and HLA-B51 was significantly higher in male, while genital ulcers and arthritis were significantly higher in female. Patients with ocular involvements showed a higher assosiation rate with neurogenic diseases and HLA-B51, and lower wih gastrointestinal manifestations. TNFα inhibitor (infliximab or adalimumab) were used for 66 cases (30%), and it could be continued for 1 year in 91%, and for 2 years in 83%. <h3>Conclusions</h3> A higher incidence of gastrointestinal manifestations was observed in patients with Behcet9s disease in Japan. Patients with ocular involvements showed a higher assosiation rate with neurogenic diseases, and lower wih gastrointestinal manifestation. Most patients could continue TNFα inhibitor safety and effectively. <h3>Disclosure of Interest</h3> None declared
FRI0182 Disease worsening and safety in patients switching from originator infliximab to biosimilar infliximab (CT-P13) in the nor-switch study: explorative analysis of RA patients
Authors: GL Goll, IC Olsen, N Bolstad, KK Jørgensen, M Lorentzen, C Mørk, J Jahnsen, EA Haavardsholm, TK Kvien
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The NOR-SWITCH study was a 52-week randomized, double-blind, non-inferiority, phase IV switch trial in patients with Crohn9s disease (CD), ulcerative colitis (UC), spondyloarthritis (SpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and plaque psoriasis (Ps) on stable treatment with originator infliximab (Remicade®, INX) and was funded by the Norwegian government. Previously, the primary analyses of the pooled indications have been published<sup>1</sup>. <h3>Objectives</h3> To investigate efficacy, safety and immunogenicity in RA patients treated with continous INX vs patients switched to CT-P13 (biosimilar infliximab, Remsima®) in the NOR-SWITCH study (explorative analyses). <h3>Methods</h3> Patients were randomized 1:1 to continued INX or switch to CT-P13. Serum drug levels were analysed in automated in-house assay. The primary endpoint was disease worsening according to disease-specific composite measures and/or consensus between investigator/patient leading to major treatment change. Exploratory subgroup analyses examined disease worsening and safety in RA. The primary endpoint was analysed using logistic regression, adjusted for diagnosis and disease duration. <h3>Results</h3> Demographics, occurence of disease worsening, change in disease measures and treatment-emergent adverse events (TEAE) were similar (Table). Serum drug levels for INX and CT-P13 were similar throughout the study (Figure) <h3>Conclusions</h3> Explorative analyses in the NOR-SWITCH study showed similar efficacy, serum drug levels and safety in RA patients switched to CT-P13 as those on continuous INX. The study was not powered to show non-inferiority within each diagnosis. <h3>References</h3> Jørgensen KK et al Switching from originator infliximab to biosimimlar CT-P13 compared to maintained treatment with originator infliximab (NOR-SWITCH): a 52-week randomized double-blind non-inferiority trial. The Lancet, in press. <h3>Disclosure of Interest</h3> G. Goll Consultant for: Orion Pharma, Pfizer, Novartis, Boeringer Ingelheim, AbbVie, I. Olsen: None declared, N. Bolstad: None declared, K. Jørgensen Consultant for: Intercept, Celltrion, Tillot, M. Lorentzen: None declared, C. Mørk Consultant for: Cellgene, AbbVie, Novartis, LeoPharma, ACOhud, Galdena Nordic, J. Jahnsen Consultant for: OrionPharma, Celltrion, Pfizer, MSD, AbbVie, Takeda, NappPharma, AstroPharma, E. Haavardsholm Consultant for: AbbVie, UCB, Roche, MSD, Pfizer, T. Kvien Consultant for: Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lily, Epirus, Hospira, Merck-serono, Novartis, Orion Pharma, Pfizer, Sandoz, UCB
SP0188 The drugs don't work
Authors: L Piggott
Journal: Annals of the Rheumatic Diseases (2017)

This presentation will depict the journey of Louise, a previous school teacher and a single mother of two, living with Fibromyalgia as well as multiple other diagnoses. Louise will discuss her feelings around being diagnosed with Fibromyalgia, how this was communicated to her and what this meant for her career and family life. Following this, Louise will share her journey through the secondary care as a Fibromyalgia patient, and her own search for answers and cure to Fibromyalgia in an attempt to salvage her life and independence, prior to accepting that this is a long-term condition which will require self-management and perseverance. In addition, Louise will share her thoughts on pain and fatigue in Fibromyalgia, and how the "drugs don9t work". <h3>Disclosure of Interest</h3> None declared
AB0534 Thrombotic microangiopathy in pregnant women with systemic lupus erythematosus: characterictics and outcomes
Authors: T Kirsanova, M Vinogradova, A Kolyvanova, N Klimenchenko
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> to evaluate the impact of thrombotic microangiopathy (TMA) on perinatal and maternal outcomes in patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> This study included 21 SLE patients with pregnancy, who developed TMA signs during pregnancy. Patients underwent general survey, clinical and laboratory assessment for disease activity and APL-antibodies. All of them had low SLE-activity indices. <h3>Results</h3> TMA signs were found in 7/21 SLE patients (33%). Patients with TMA had significantly higher systolic and diastolic blood pressure (P≤0.05), higher serum creatinine and lower estimated glomerular filtration rate (P≤0.05) than that of those without TMA lesions (tabl.1). APLA positivity was significantly more frequent in patients with TMA (3/7 vs 0/14). TMA onset in 2 patients occurred before 20 gestational weeks, 5/7 have developed PE signs (23–38 weeks), only 3/7 had classical HELLP syndrome. There was no PE in patients without TMA. There was a significant association between the detection of TMA and adverse perinatal outcomes (tabl.2). Patient with TMA and SLE had a poor outcome and most severe course: 5/7 had a PE (3/7 developed HELLP),3/7 had antenatal fetal death, 3/7had signs of heart damage,5/7 a variety of neurological manifestations. Despite of PE signs in 5/7 with TMA the blood sFlt1/PLGF levels were slightly above normal (average sFlt/PLGF levels in preeclampsia without SLE in our another study is 404,47) <h3>Conclusions</h3> TMA is not an uncommon disorder in pregnant patients with SLE. It is associated with APLA positivity only in 1/3 cases. TMA was significantly associated with renal impairment, systemic hypertension and adverse perinatal outcomes. Less increased ratio of sFlt-1/PlGF in TMA patients than "pure" PE may confirm that PE in patients with TMA is not a condition due to angiogenic factors imbalance. Circulating concentrations of angiogenic factors appear not to be suitable markers to assess the severity of PE and adverse outcomes in SLE patients. Thus, TMA may be an important cause of renal injury and renal dysfunction in a subset of pregnant patients with SLE and associated with worse renal and perinatal prognosis. Complement over-activation via both classical (SLE+APS) and alternative pathways might play an important role in the pathogenesis of TMA in SLE. <h3>Disclosure of Interest</h3> None declared
Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia
Authors: S Takao, W Chien, V Madan, D-C Lin, L-W Ding, Q-Y Sun, A Mayakonda, M Sudo, L Xu, Y Chen, Y-Y Jiang, S Gery, M Lill, E Park, W Senapedis, E Baloglu, M Müschen, H P Koeffler
Journal: Leukemia (2017)
Nano-sized metabolic precursors for heterogeneous tumor-targeting strategy using bioorthogonal click chemistry in vivo
Authors: Sangmin Lee, Seulhee Jung, Heebeom Koo, Jin Hee Na, Hong Yeol Yoon, Man Kyu Shim, Jooho Park, Jong-Ho Kim, Seulki Lee, Martin G. Pomper, Ick Chan Kwon, Cheol-Hee Ahn, Kwangmeyung Kim
Journal: Biomaterials (2017)
Increased Level of Interleukin 6 Associates With Increased 90-Day and 1-Year Mortality in Patients With End-Stage Liver Disease
Authors: Johannes Remmler, Christoph Schneider, Theresa Treuner-Kaueroff, Michael Bartels, Daniel Seehofer, Markus Scholz, Thomas Berg, Thorsten Kaiser
Journal: Clinical Gastroenterology and Hepatology (2017)
Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota
Authors: Guolin Li, Cen Xie, Siyu Lu, Robert G. Nichols, Yuan Tian, Licen Li, Daxeshkumar Patel, Yinyan Ma, Chad N. Brocker, Tingting Yan, Kristopher W. Krausz, Rong Xiang, Oksana Gavrilova, Andrew D. Patterson, Frank J. Gonzalez
Journal: Cell Metabolism (2017)
GP73 - a novel cancer-specific antigen
Authors: Laura Brennan, Michael Amatulli, Jaimie Slade, Yuan Cheng, Paul Balderes, Yan Wu, Yaron Hadari, Keren Paz
Journal: Cancer Research (2008)

4912  The fate of the eukaryotic cell is dictated in large by its protein content and their localization. Mounting evidence gathered during the last decades implicates a crucial role of aberrant protein expression and mutagenesis in the cancerous process. A novel class of modification that may contribute to cellular transformation is an alteration in protein distribution. The translocation of proteins between different cellular compartments must be tightly controlled in normal cells and healthy tissue. Deviations in the protein transport machinery and the resultant protein miss localization might lead to abnormalities that are associated with excessive, uncontrolled cell proliferation. In this study, we undertook to identify plasma-membrane associate cancer-specific antigens. Mice were immunized with breast tumor-derived extracts. Hybridoma clones were isolated and characterized. We report herein the identification of GP73, a 73 kDa resident Golgi membrane protein of unknown function that is expressed on plasma membrane of tumor cells but not on normal cells. The role of GP73 in cell proliferation is currently investigated.
Behavioral Economics and Health Insurance Reform—Reply
Authors: Jonathan Skinner, Kevin G. Volpp
Journal: JAMA (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 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
OP0109 Is mental health comparabale in rheumatoid and psoriatic arthritis patients? a comparative analysis of real life longitudinal data from the nor-dmard study
Authors: B Michelsen, E Lie, KM Fagerli, EK Kristianslund, HB Hammer, G Haugeberg, TK Kvien
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Only few studies have compared health related quality of life (HRQoL) between rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. <h3>Objectives</h3> To compare the Medical Outcomes Survey Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) in RA and PsA patients from a large prospective observational registry. <h3>Methods</h3> We included RA and PsA patients from the prospective observational multicenter Norwegian-Disease-Modifying Antirheumatic Drug (NOR-DMARD) study, who started first-time tumour necrosis factor inhibitors or DMARD naïve patients starting methotrexate between year 2000 and 2012. Continuous variables were compared using independent t-test (normally distributed data). Prespecified ANCOVA analyses adjusted for age, gender and years since diagnosis were performed to compare SF-36 PCS and MCS between the RA and PsA patients at baseline and after 3 and 6 months follow-up. <h3>Results</h3> A total of 2735 RA and 1236 PsA patients were included. Mean (SD) age was 55.0 (13.5)/ 48.3 (12.4) years, median (25th-75th percentile) years since diagnosis 0.7 (0.02–6.4)/ 1.3 (0.09–7.7), 69.7/48.4% were women and 31.7/29.8% current smokers. Mean (SD) 28-joint Disease Activity Score was higher in RA vs. PsA patients at baseline (4.9 (1.4)/ 4.2 (1.3)) and at 3 (3.6 (1.5)/ (3.1 (1.4)) and 6 months follow-up (3.3 (1.4)/ 3.0 (1.3)), respectively (p≤0.001). Unadjusted means (SD) of SF-36 PCS and MCS were similar between the RA and PsA patients (Table 1). In adjusted analyses SF-36 PCS was slightly higher and SF-36 MCS similar between RA and PsA patients at 3 and 6 months follow-up (Table 2). <h3>Conclusions</h3> Mental HRQoL reflected through SF-36 MCS was similar between RA and PsA patients at all time points, in spite of slightly worse physical HRQoL reflected through lower SF-36 PCS in the PsA group at 3 and 6 months follow-up. <h3>Disclosure of Interest</h3> B. Michelsen: None declared, E. Lie Consultant for: Hospira, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, K. Fagerli: None declared, E. Kristianslund: None declared, H. Hammer Consultant for: AbbVie, Pfizer, UCB, Roche, MSD, BMS and Novartis., Speakers bureau: AbbVie, Pfizer, UCB, Roche, MSD, BMS and Novartis., G. Haugeberg: None declared, T. Kvien Consultant for: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz and UCB, Speakers bureau: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz and UCB
Classifying the evolutionary and ecological features of neoplasms
Authors: Carlo C. Maley, Athena Aktipis, Trevor A. Graham, Andrea Sottoriva, Amy M. Boddy, Michalina Janiszewska, Ariosto S. Silva, Marco Gerlinger, Yinyin Yuan, Kenneth J. Pienta, Karen S. Anderson, Robert Gatenby, Charles Swanton, David Posada, Chung-I Wu, Joshua D. Schiffman, E. Shelley Hwang, Kornelia Polyak, Alexander R. A. Anderson, Joel S. Brown, Mel Greaves, Darryl Shibata
Journal: Nature reviews. Cancer (2017)

Based on a consensus conference of experts in the evolution and ecology of cancer, this article proposes a framework for classifying tumours that includes four evolutionary and ecological processes: neoplastic cell diversity and changes over time in that diversity, hazards to cell survival and available resources. Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components. These are the diversity of neoplastic cells (intratumoural heterogeneity) and changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the hazards to neoplastic cell survival and the resources available to neoplastic cells, which make up an ecological index (Eco-index). We review evidence demonstrating the importance of each of these factors and describe multiple methods that can be used to measure them. Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient's tumour. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research.