tbuckley/cabot-search huggingface dataset:
AB1150 ECONOMIC IMPACT ASSOCIATED TO BIOLOGICAL THERAPY / SYNTHETIC FAME OPTIMIZATION IN A COHORT OF PATIENTS WITH CHRONIC INFLAMMATORY RHEUMATIC DISEASES TREATED BY OBJECTIVES.
Authors: P. Castro, A. Onteniente
Journal: Annals of the Rheumatic Diseases (2020)

Background: Therapeutic decision-making for biologic-therapies/ synthetic FAME (BT/SD) dose optimization, should be based on optimal disease activity results according to a treatment strategy by objectives. The goal of BT optimization is to guarantee long-term effectiveness and safety, maximising economic savings Objectives: To evaluate BT optimization patterns in patients with rheumatic diseases (RD) and associated economic savings. Methods: An observational and prospective study, which included a cohort of patients with rheumatoid arthritis (RA), spondyloarthropathies (SA) and psoriatic arthritis (PsA) treated with BT from January 2014 to December 2019. BT optimization, achieved by reducing or prolonging the interval at least one dose, was indicated when patients have more than 6 months of treatment and are in clinical remission (DAS28 &lt;2.6 for RA and PsA, and BASDAI&lt;2 for SA) or minimal clinical activity (DAS28&lt;3.2 for RA and PsA, and BASDAI&lt;4 for SA). Variables were described as frequencies and means. Diagnosis, BT (abatacept, adalimumab, apremilast, baricitinib, certolizumab, etanercept, golimumab, ixekizumab, secukinumab, tocilizumab, tofacitinib, and ustekinumab), dose regimens, total treatment duration, time on BT optimization (TO) and treatment costs were collected. Cost savings were calculated per patient by comparing optimization treatment costs to conventional treatment and globally by comparing real cost to theoretical conventional doses cost. Results: A total of 260 patients were included in the study. Switching were observed in 32.7%. From all patients, 53% were candidates for BT optimization (according to diagnosis: 60.9% with RA, followed by 52.2% with SA and 43.4% with PsA) A 40% of patients with BT optimization were treated with adalimumab and etanercept being also the most common BT used in RD treatment BT optimization allowed a pharmaceutical saving of € 177,539.40 per year against the use of conventional therapy, resulting in a reduction of the total cost of €1,065,236.40 in the last 6 years. The saving per patient / year was € 707.63 for RA; € 850,40 for SA and of €493,21 for the PsA. Conclusion: Therapeutic decision-making based on validated disease activity scales has allowed the BT optimization in approximately 53% of patients with RD. BT optimization allowed a pharmaceutical saving of € 177,539.40 per year being higher in the SA (€ 850.40) followed by the RA (€ 707.63) and finally the PsA (€ 493.21) The BT optimization allows to reduce costs maintaining the effectiveness and safety. Disclosure of Interests: None declared
Assessing Quantitative Comparisons of Health and Social Care Between Countries
Authors: Michelle D. Carlson, Brita Roy, A. Stef Groenewoud
Journal: JAMA (2020)

This Viewpoint discusses differences that complicate cross-country comparisons of health and social services and proposes a framework for assessing the appropriateness of those comparisons to help researchers improve their investigations and help readers critically appraise them.
Comparison of Driving Times to Opioid Treatment Programs and Pharmacies in the US
Authors: Robert A. Kleinman
Journal: JAMA Psychiatry (2020)

Methadone maintenance is an effective treatment of opioid use disorder, but federal regulations in the US restrict methadone dispensing to opioid treatment programs (OTPs). In Australia, Canada, and the UK, patients can obtain methadone maintenance from community pharmacies.To compare driving access to methadone maintenance treatment between OTP and pharmacy dispensing models.This descriptive cross-sectional study assessed driving times from census tract mean centers of population to OTPs and pharmacies. Census tracts from the 50 US states and the District of Columbia (based on the 2010 US Census) were included if their population was greater than 0, if their mean center of population (MCP) was within 3 miles of the road network, and if the 1-way driving times from the census tract MCP to both an OTP and a pharmacy were 12 hours or less. Data analyses were performed from November 15, 2019, to April 18, 2020.The primary outcome was the population-weighted mean driving time from census tract MCPs to OTPs and pharmacies in the US. Census tract MCPs are population-weighted geographic centroids of residents living in each census tract. Driving times were estimated using historical average driving speeds.All 1682 unique locations of OTPs were included, and 69 475 unique pharmacy locations were included after geocoding. A total of 72 443 census tracts were included in the analysis. The mean population-weighted driving time from census tract MCPs was 20.4 minutes (95% CI, 20.3-20.6 minutes) to OTPs and 4.5 minutes (95% CI, 4.4-4.5 minutes) to pharmacies (P < .001). Differences in driving time, distance, and cost between 1-way trips ending at OTPs and pharmacies were largest in micropolitan and noncore counties.In this study, population-weighted mean driving times from US census tract MCPs were longer to OTPs than to pharmacies.
AB0163 Plain radiography findings in patients with low back pain
Authors: Y Akkoc, Y Kirazli, F Erer, G Celeboglu
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> This study was performed to investigate the radiopathological findings based on plain radiographic examinations of patients with low back pain. <h3>Methods</h3> In the present study, we have examined 747 patients, with a mean age of 47.97 years, 488 (65.32%) were women and 259 (34.67%) were men. Plain antero-posterior and lateral lumbosacral vertebrae radiographes were obtained from the patients and were examined in regard to the presence of congenital abnormalities (sacralisation, lumbarisation, spina bifida), lumbar degenerative disc disease, spondylolisthesis and osteoporosis. Kellgren-Lawrence’s scoring system was used to assess the presence of degenerative disc disease. Increased vertebral radiolucency, accentuation of vertebral endplates and prominence of vertical trabeculae due to relative loss of horizontal trabeculae were accepted as radiological findings of osteoporosis. <h3>Results</h3> It was found that degenerative disc disease (29.58%) was the most frequently encountered radiopathological finding, followed by osteoporosis (23.3%) and congenital abnormalities (21.15%). Spondylolisthesis (6.02%) was relatively rare. The most common congenital abnormality was sacralisation (17.67%). Degenerative disc disease was most frequently seen at L4-L5 and L5-S1 levels. When the radiopathological findings were analysed according to sex distribution, there was no significant difference between women and men, except for osteoporosis. <h3>Conclusion</h3> The results of this study showed that degenerative disc disease was the most frequently seen radiopathological finding, followed by osteoporosis, congenital abnormalities and spondylolisthesis in patients with low back pain.
Effects of influenza vaccination on the risk of cardiovascular and respiratory diseases and all-cause mortality
Authors: Yangyang Cheng, Xinxi Cao, Zhi Cao, Chenjie Xu, Li Sun, Ying Gao, Yuan Wang, Shu Li, Cunjin Wu, Xin Li, Yaogang Wang, Sean X. Leng
Journal: Ageing Research Reviews (2020)
The Conundrum of the Association of Chemotherapy With Survival Outcomes Among Elderly Patients With Curable Luminal Breast Cancer
Authors: Nicolò Matteo Luca Battisti, Amelia McCartney, Laura Biganzoli
Journal: JAMA Oncology (2020)

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
Abstract 1782: ANKRD52 inhibited tumor metastasis through dephosphorylation of PAK1 in lung adenocarcinomas
Authors: Ting-Fang Lee, Yin-Pu Liu, Yen-Fan Lin, Chong-Fang Hsu, Cheng-Wen Wu
Journal: Cancer Research (2019)

Abstract PAK1 is an important oncogene involved in the progression of a variety of cancer types including lung cancer. Although PAK1 inhibition is shown to suppress tumor progression, specific PAK1 inhibitors are not available due to the complex structure and insufficient understanding of this protein. In an attempt to find TAZ (WW domain-containing transcription regulator 1) regulated tumor suppressor, a member of ankyrin repeat proteins, ankyrin repeat domain 52 (ANKRD52), is observed to suppress PAK1 phosphorylation. Ankyrin repeat proteins are known to function as a platform for protein-protein interactions, and ANKRD52 was shown to interact with protein phosphatase 6 (PP6). Immunohistochemistry staining in lung cancer tissue revealed prolonged disease-free survival in high ANKRD52 expressing cases. Using lung cancer cell lines, ANKRD52 knockdowns showed significantly increased cell mobility while forced expressed ANKRD52 decreased cell mobility. Using mass spectrometry analysis, p21-activated kinases (PAK1) was identified to interact with ANKRD52. Upregulated PAK1 phosphorylation was detected in the knockdowns of ANKRD52 or PP6. Our model demonstrated a novel anti-metastatic protein, ANKRD52, that regulates cell mobility through interactions with PP6 and dephosphorylation of PAK1. Citation Format: Ting-Fang Lee, Yin-Pu Liu, Yen-Fan Lin, Chong-Fang Hsu, Cheng-Wen Wu. ANKRD52 inhibited tumor metastasis through dephosphorylation of PAK1 in lung adenocarcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1782.
PWAS: proteome-wide association study—linking genes and phenotypes by functional variation in proteins
Authors: Nadav Brandes, Nathan Linial, Michal Linial
Journal: Genome biology (2020)

We introduce Proteome-Wide Association Study (PWAS), a new method for detecting gene-phenotype associations mediated by protein function alterations. PWAS aggregates the signal of all variants jointly affecting a protein-coding gene and assesses their overall impact on the protein's function using machine learning and probabilistic models. Subsequently, it tests whether the gene exhibits functional variability between individuals that correlates with the phenotype of interest. PWAS can capture complex modes of heritability, including recessive inheritance. A comparison with GWAS and other existing methods proves its capacity to recover causal protein-coding genes and highlight new associations. PWAS is available as a command-line tool.
FRI0044 Early treatment with dmards improves radiological outcome in patients with rheumatoid arthritis
Authors: CF Allaart, JW Wieringa, TW Huizinga, FC Breedveld
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> For years, patients with rheumatoid arthritis were treated with DMARDs only if they showed severe disease progression with insufficient relieve with NSAIDs. Anti-malarials were prescribed more often than methotrexate and sulphasalazin. However, since side effects of DMARDs and NSAIDs have been shown to be similar, and because it is apparent that radiological damage occurs early in the course of rheumatoid arthritis, rheumatologists have gradually become more aggressive in the treatment of RA: DMARDs, especially methrotrexate and sulphasalazin, are prescribed earlier and in higher dosages, sometimes also in combinations. Do the patients benefit from this change in attitude? <h3>Objectives</h3> <h3>Methods</h3> Since 1993 patients with recent onset arthritis are seen and followed up in our Early Arthritis Clinic. In a retrospective study of all patients who were diagnosed in 1994 (n = 28) and 1998 (n = 52) with RA and probable RA (1 in 1994, 2 in 1998), we evaluated the erosion progression (Sharp/van der Heijde method) between the time of presentation and 2 years later. <h3>Results</h3> in 1994, 28 patients and in 1998, 52 patients were diagnosed with RA or probable RA (n = 1, n = 2, resp.). At presentation, there were no differences in sex distribution, mean age, duration of symptoms, number of inflamed joints, mean ESR, percentage positive for Rheumatoid Factor-IgG, or Sharp/van der Heijde score. Mean duration after presentation before a DMARD was started in 1994 was 7.9 months, in 1998 1,8 months. After 2 years follow-up, 36% of patients included in 1994 were still without DMARD-treatment, and of 36% who started on antimalarials, 60% were still on those drugs. Of the patients included in 1998, 4% had received no DMARDs in the next 2 years, and 63% resp. 13% received sulphasalazin resp. methotrexate as first drug. Of the 20% who started on antimalarials, 60% had discontinued and started another DMARD after on average 6 months. The average progression of the Sharp/van der Heijde score was 36.5 for the patients included in 1994, and 9.5 for those included in 1998. <h3>Conclusion</h3> Changes in perception of how to treat RA, inspired by less fear for side effects of DMARDs and awareness of early joint destruction, have resulted in less erosion progression in the patients.
Metabolic inflammation in heart failure with preserved ejection fraction
Authors: Gabriele G Schiattarella, Daniele Rodolico, Joseph A Hill
Journal: Cardiovascular Research (2020)

Abstract One in 10 persons in the world aged 40 years and older will develop the syndrome of HFpEF (heart failure with preserved ejection fraction), the most common form of chronic cardiovascular disease for which no effective therapies are currently available. Metabolic disturbance and inflammatory burden contribute importantly to HFpEF pathogenesis. The interplay within these two biological processes is complex; indeed, it is now becoming clear that the notion of metabolic inflammation—metainflammation—must be considered central to HFpEF pathophysiology. Inflammation and metabolism interact over the course of syndrome progression, and likely impact HFpEF treatment and prevention. Here, we discuss evidence in support of a causal, mechanistic role of metainflammation in shaping HFpEF, proposing a framework in which metabolic comorbidities profoundly impact cardiac metabolism and inflammatory pathways in the syndrome.
Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629)
Authors: Jean-Jacques Grob, Rene Gonzalez, Nicole Basset-Seguin, Olga Vornicova, Jacob Schachter, Abhishek Joshi, Nicolas Meyer, Florent Grange, Josep M. Piulats, Jessica R. Bauman, Pingye Zhang, Burak Gumuscu, Ramona F. Swaby, Brett G. M. Hughes
Journal: Journal of Clinical Oncology (2020)

Treatment options are limited for patients with recurrent and/or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC); mortality rates exceed 70% in patients with distant metastases. Here, we present the first interim analysis of the R/M cSCC cohort from the 2-cohort-locally advanced and R/M-phase II KEYNOTE-629 study.
Hemolysis transforms liver macrophages into antiinflammatory erythrophagocytes
Authors: Marc Pfefferlé, Giada Ingoglia, Christian A. Schaer, Ayla Yalamanoglu, Raphael Buzzi, Irina L. Dubach, Ge Tan, Emilio Y. López-Cano, Nadja Schulthess, Kerstin Hansen, Rok Humar, Dominik J. Schaer, Florence Vallelian
Journal: Journal of Clinical Investigation (2020)

During hemolysis, macrophages in the liver phagocytose damaged erythrocytes to prevent the toxic effects of cell-free hemoglobin and heme. It remains unclear how this homeostatic process modulates phagocyte functions in inflammatory diseases. Using a genetic mouse model of spherocytosis and single-cell RNA sequencing, we found that erythrophagocytosis skewed liver macrophages into an antiinflammatory phenotype that we defined as MarcohiHmoxhiMHC class IIlo erythrophagocytes. This phenotype transformation profoundly mitigated disease expression in a model of an anti-CD40-induced hyperinflammatory syndrome with necrotic hepatitis and in a nonalcoholic steatohepatitis model, representing 2 macrophage-driven sterile inflammatory diseases. We reproduced the antiinflammatory erythrophagocyte transformation in vitro by heme exposure of mouse and human macrophages, yielding a distinctive transcriptional signature that segregated heme-polarized from M1- and M2-polarized cells. Mapping transposase-accessible chromatin in single cells by sequencing defined the transcription factor NFE2L2/NRF2 as a critical driver of erythrophagocytes, and Nfe2l2/Nrf2 deficiency restored heme-suppressed inflammation. Our findings point to a pathway that regulates macrophage functions to link erythrocyte homeostasis with innate immunity.
サイクリン依存性キナーゼ-9,p300/GATA-4複合体の新規構成物として,はマウスES細胞の心筋細胞への分化に関連する
Authors: Kaichi Shinji, Takaya Tomohide, Morimoto Tatsuya, Sunagawa Yoichi, Kawamura Teruhisa, Ono Kou, Kita Toru, Hidaka Kyoko, Morisaki Takayuki, Baba Shiro, Heike Toshio, Nakahata Tatsutoshi, Hasegawa Kouji
Journal: Circulation (2007)
Comparison of Reported Deaths From COVID-19 and Increase in Total Mortality in Italy
Authors: Manfredi Rizzo, Luca Foresti, Nicola Montano
Journal: JAMA Internal Medicine (2020)

could increase the likelihood of patients presenting to the ED before a major thunderstorm, we found no association between thunderstorms and ED visits for control conditions like sepsis or pulmonary embolism.Assuming an average 65 years or older population of 37.7 million Americans (based on census data), approximately 52 000 additional respiratory ED visits were estimated to occur in the 3 or more days surrounding major storms during the 14-year study period.Discussion | Emergency visits for acute respiratory illness significantly increased during the days before major thunderstorms among Medicare beneficiaries, particularly those with asthma and/or COPD.Visits were temporally associated with rises in temperature and particulate matter concentrations, atmospheric changes that have previously been associated with acute respiratory illness in the Medicare population. 3,4are epidemics of asthma following thunderstorms in other countries have been hypothesized to result from pollen grains rupturing when wet, allowing winds to carry small pollen particles that can trigger allergic asthma in susceptible patients. 5In this study, ED visits peaked before the thunderstorm, suggesting pollen particle release from precipitation was not the dominant mechanism.A limitation of this study is that it may not generalize to younger populations for which allergic asthma is common. 6 To our knowledge, this is the first large-scale study to evaluate the association between thunderstorms and emergency visits for respiratory illness.Our findings suggest antecedent rises in particulate matter concentration and te m p e r at u re m ay b e t h e d o m i n a nt m e c h a n i s m o f thunderstorm-associated acute respiratory disease
IL-15 Preconditioning Augments CAR T Cell Responses to Checkpoint Blockade for Improved Treatment of Solid Tumors
Authors: Lauren Giuffrida, Kevin Sek, Melissa A. Henderson, Imran G. House, Junyun Lai, Amanda X.Y. Chen, Kirsten L. Todd, Emma V. Petley, Sherly Mardiana, Izabela Todorovski, Emily Gruber, Madison J. Kelly, Benjamin J. Solomon, Stephin J. Vervoort, Ricky W. Johnstone, Ian A. Parish, Paul J. Neeson, Lev M. Kats, Phillip K. Darcy, Paul A. Beavis
Journal: Molecular Therapy (2020)

Chimeric antigen receptor (CAR) T cell therapy has been highly successful in hematological malignancies leading to their US Food and Drug Administration (FDA) approval. However, the efficacy of CAR T cells in solid tumors is limited by tumor-induced immunosuppression, leading to the development of combination approaches, such as adjuvant programmed cell death 1 (PD-1) blockade. Current FDA-approved methods for generating CAR T cells utilize either anti-CD3 and interleukin (IL)-2 or anti-CD3/CD28 beads, which can generate a T cell product with an effector/exhausted phenotype. Whereas different cytokine preconditioning milieu, such as IL-7/IL-15, have been shown to promote T cell engraftment, the impact of this approach on CAR T cell responses to adjuvant immune-checkpoint blockade has not been assessed. In the current study, we reveal that the preconditioning of CAR T cells with IL-7/IL-15 increased CAR T cell responses to anti-PD-1 adjuvant therapy. This was associated with the emergence of an intratumoral CD8+CD62L+TCF7+IRF4- population that was highly responsive to anti-PD-1 therapy and mediated the vast majority of transcriptional and epigenetic changes in vivo following PD-1 blockade. Our data indicate that preservation of CAR T cells in a TCF7+ phenotype is crucial for their responsiveness to adjuvant immunotherapy approaches and should be a key consideration when designing clinical protocols.
Trends in Participation and Authorship of Women at the Pacific Coast Surgical Association Meeting, 2008-2018
Authors: Sarah K. Lee, Jenny Chang, Nikita Kadakia, Naveenraj L. Solomon, Carlos A. Garberoglio, Ahmed M. Abou-Zamzam, Sharon S. Lum
Journal: JAMA Surgery (2020)

This study investigates temporal trends in gender participation in membership, leadership, and presentations of women in the Pacific Coast Surgical Association.
Omalizumab restores the ability of human plasmacytoid dendritic cells to induce Foxp3<sup>+</sup>Tregs
Authors: Jacobo López-Abente, Cristina Benito-Villalvilla, Xavier Jaumont, Pascal Pfister, Paolo Tassinari, Oscar Palomares
Journal: European Respiratory Journal (2020)

<b>IgE-FcεR1 cross-linking on human pDCs impairs their capacity to generate regulatory T-cells and <i>in vitro</i> omalizumab restores this ability. These findings may pave the way for novel biomarkers to assess omalizumab clinical efficacy and responder patients.</b>https://bit.ly/2ZQbJ9t
Government must amend trade bill to exclude NHS from future deals, doctors say
Authors: Gareth Iacobucci
Journal: BMJ (2020)

More than 400 doctors and health professionals have urged the government to accept amendments to its trade bill to ensure that health services are not on the table in future trade deals.

An open letter sent to ministers ahead of a UK parliamentary debate on Monday 20 July on the UK Trade Bill argues that if protection of the NHS were not written into the legislation the health service will be on the table in future trade deals.1

The letter says, …
Abstract 14605: A Meta Analysis of Pre-operative Stress Testing in the Evaluation of Patients Undergoing Non-Cardiac Surgery
Authors: Heidi C Nicewarner, Bindu Kalesan, Sunny S Intwala, Christopher K Leung, Gary J Balady
Journal: Circulation (2017)

Introduction: Pre-operative stress testing prior to non-cardiac surgery is widely used, but its value in predicting peri-operative mortality is uncertain. A comprehensive meta-analysis was performe...