tbuckley/cabot-search huggingface dataset:
AB0883 SYSTEMIC INFLAMMATION AND ATHEROSCLEROSIS IN PATIENTS WITH GOUT. RESULTS FROM THE NOR-GOUT STUDY
Authors: Silvia Rollefstad, Till Uhlig, Lars Fridtjof Karoliussen, Hilde Berner Hammer, Anne Grete Semb
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The association between gout and cardiovascular disease (CVD) is well known,<sup>1</sup> whereas mechanisms behind this association are poorly understood. <h3>Objectives</h3> This study aimed to evaluate factors associated with asymptomatic carotid atherosclerosis in patients with gout. <h3>Methods</h3> In this prospective study patients with crystal-proven gout were included after a recent disease flare, if the serum urate level was &gt;360 μmol/L (&gt;6 mg/dl). We analysed baseline data in patients without established CVD who were referred to a CVD risk evaluation, including ultrasound of the carotid arteries, blood pressure measurement and laboratory tests. Carotid atherosclerotic plaques were defined in the longitudinal view as protrusions into the lumen of ≥1.5 mm or at least 2 times the adjacent intima-media thickness according to the Mannheim criteria. <h3>Results</h3> Of the 79 gout patients included, approximately 10% were females, and mean (SD) age was 52.1±13.1 years. Thirty-two (40.5%) had carotid plaques (Table). Only 9.3% were current smokers, while mean (SD) body mass index was high (29.1±4.7 kg/m<sup>2</sup>). Lipids were in the normal range, with a mean (SD) total cholesterol at 5.3±1.09 mmol/L and low density lipoprotein cholesterol 3.12±0.95 mmol/L. Systolic blood pressure was in the normal range 134.0±15.1 mmHg, although 29.1% of the patients were treated with antihypertensive agents. In univariate analyses, higher age, hypertension and higher erythrocyte sedimentation rate (as a marker of systemic inflammation) were significantly associated with the presence of carotid plaques (p=0.01 and p=0.04, respectively) (Figure). Serum urate levels or disease duration were not associated with carotid plaques (p=0.27 and p=0.44, respectively). <h3>Conclusion</h3> Our results indicate an association between systemic inflammation and atherosclerosis in patients with gout. To be able to efficiently prevent CVD in this patient group, prospective studies with larger sample sizes are needed to elucidate the mechanisms behind the increased risk of CVD in gout patients. <h3>References</h3> [1] Choi HK, Curhan G. Independent impact of gout on mortality and risk of coronary heart disease. Circulation2007;116:894-900. <h3>Disclosure of Interests</h3> Silvia Rollefstad: None declared, Till Uhlig Consultant for: Grünenthal, Novartis, Speakers bureau: Grünenthal, Novartis, Lars Fridtjof Karoliussen: None declared, Hilde Berner Hammer Grant/research support from: AbbVie, Pfizer and Roche, Paid instructor for: AbbVie, Pfizer, UCB, Novartis, Roche, Speakers bureau: AbbVie, Pfizer, UCB, Novartis, Roche, Anne Grete Semb: None declared
Abstract 16117: The Influence of Polymorphisms in DC-SIGN With Kawasaki Disease (KD) Susceptibility and Treatment Outcomes in Hispanics
Authors: Sadeep Shrestha, Howard W Wiener, Aditi Shendre, Michael A Portman
Journal: Circulation (2011)

Functional polymorphisms of the C-type lectin CD209 (DC-SIGN) affect susceptibility to infection by viruses including HIV by modulating immune response. DC-SIGN has also been identified as a specif...
Development and analysis of Wilms’ tumor protein (WT1) specific T cells for adoptive immunotherapy of epithelial ovarian cancer
Authors: Jakob Dupont, Ekaterina S. Doubrovina, Chia Ma, Amanda Hummer, Robert Soslow, Richard J. O’Reilly
Journal: Cancer Research (2005)

4251  The Wilms’ tumor protein (WT1), which is overexpressed by a number of human cancers, is an emerging target for cancer immunotherapy. Epithelial Ovarian Cancers (EOC) differentially express certain onco fetal proteins normally present on other tissues only during embryonal development. We sought to evaluate whether the onco fetal protein WT1 was present in EOC and whether it represented a potential immunotherapeutic target for patients with EOC. We evaluated 86 primary ovarian tumor specimens, representing all major histologic subtypes, for WT1 expression by immunohistochemistry (IHC). We found that WT1 overexpression was present in 28/86 (33%) of tumor samples and was associated with serous histology (16/25, 64%) (p=0.001) while only 1/17 (6%) borderline tumors overexpressed the antigen. Thus, WT1 tumor expression was correlated with poor clinical outcome. Furthermore, ELISA evaluation of patient serum revealed 8/32 (25%) of EOC patients had native anti-WT1 antibody responses at a dilution of 1:400. Recently, we and others have identified potentially immunogenic peptides derived from WT1 which bind the common HLA alleles, HLA A0201, A0301, and A2402. These peptide antigens have been used to stimulate and expand WT1-specific T cells. We use autologous EBV transformed B cells (BLCL), isolated from EOC patients, either pulsed with immunogenic WT1 peptides or transfected with vectors encoding the WT1 gene to sensitize and expand WT1-specific T cells form EOC patients, in vitro. This sensitization reliably generated WT1-tetramer positive T cells (range 2-7% tetramer positive) from patients after 4 stimulations over 28 days. Thirty to 210 x 106 cells, with a predominance of CD8+ cells, could be generated over the 28 days. The T cells sensitized with WT1 generate IFNg and other cytokines in response to peptide and specifically lyse primary HLA A2+ WT1+ ovarian or leukemia tumor cells in vitro. Non-WT1 and non-HLA matched tumor cells were not lysed. In a SCID mouse, human tumor xenograft model, we found that adoptively transferred WT1 specific HLA A2+ T cells (two doses of 16 x 106 T cells) home to and specifically induce regressions of established HLA A2+ WT1+ ovarian cancer while the T cells did not home to nor regress non-WT1 or non-HLA matched tumors in the same animals. Due to the frequent expression of WT1 in EOC and the practicable approach of using autologous EBV BLCL to sensitize tumoricidal WT1 T cells from patients, WT1 represents a viable target for adoptive immunotherapy of EOC.
Interferon Signaling Is Diminished with Age and Is Associated with Immune Checkpoint Blockade Efficacy in Triple-Negative Breast Cancer
Authors: Jaclyn Sceneay, Gregory J. Goreczny, Kristin Wilson, Sara Morrow, Molly J. DeCristo, Jessalyn M. Ubellacker, Yuanbo Qin, Tyler Laszewski, Daniel G. Stover, Victor Barrera, John N. Hutchinson, Rachel A. Freedman, Elizabeth A. Mittendorf, Sandra S. McAllister
Journal: Cancer Discovery (2019)

Immune checkpoint blockade (ICB) therapy, which targets T cell-inhibitory receptors, has revolutionized cancer treatment. Among the breast cancer subtypes, evaluation of ICB has been of greatest interest in triple-negative breast cancer (TNBC) due to its immunogenicity, as evidenced by the presence of tumor-infiltrating lymphocytes and elevated PD-L1 expression relative to other subtypes. TNBC incidence is equally distributed across the age spectrum, affecting 10% to 15% of women in all age groups. Here we report that increased immune dysfunction with age limits ICB efficacy in aged TNBC-bearing mice. The tumor microenvironment in both aged mice and patients with TNBC shows decreased IFN signaling and antigen presentation, suggesting failed innate immune activation with age. Triggering innate immune priming with a STING agonist restored response to ICB in aged mice. Our data implicate age-related immune dysfunction as a mechanism of ICB resistance in mice and suggest potential prognostic utility of assessing IFN-related genes in patients with TNBC receiving ICB therapy. SIGNIFICANCE: These data demonstrate for the first time that age determines the T cell-inflamed phenotype in TNBC and affects response to ICB in mice. Evaluating IFN-related genes from tumor genomic data may aid identification of patients for whom combination therapy including an IFN pathway activator with ICB may be required.This article is highlighted in the In This Issue feature, p. 1143.
Association Between Food Insecurity and Migraine Among US Young Adults
Authors: Jason M. Nagata, Sheri D. Weiser, Holly C. Gooding, Andrea K. Garber, Kirsten Bibbins-Domingo, Kartika Palar
Journal: JAMA Neurology (2019)

This study examines the association between food insecurity and migraine in a nationally representative sample of US young adults.
PS1589 RETROSPECTIVE ANALYSIS OF HEMOGLOBIN LEVEL IN 500 TRANSFUSION EVENTS AS A STUDY MODEL FOR THE EVALUATION OF TRANSFUSION APPROPRIATENESS
Authors: R. Crocchiolo, I. Cuppari, E. Boiani, C. Cesana, G. Cornacchini, A. Ferrera, G. Lando, A.M. Mazza, M.T. Pugliano, L. Sica, E. Volpato, S. Rossini
Journal: HemaSphere (2019)

Background: The hemoglobin (Hb) value adopted in the real life setting for the clinical decision of packed red blood cell (RBC) transfusion (transfusion trigger) is sometimes difficult to accurately retrieve and could be different to what is indicated in the blood request. The identification of the transfusion trigger is critical for the analysis of the distinct physicians’ attitudes across the different units within the same hospital and for the dissection of transfusion appropriateness. Aims: The aims of the present analysis is to compare the transfusion trigger across the multiple medical and surgical units at our Center and to describe the Hb values before and after the transfusion events. Further, considerations about the feasibility and the potential applications of this analytical approach are discussed. Methods: Data extraction procedure focused on the first semester 2018, dealing with transfusion episodes of 1–2 packed RBCs administered to patients hospitalised at ASST GOM Niguarda, Milan, Italy. Each single episode was registered, regardless of the number of the total packed RBCs transfused, as well as the Unit where the patient was admitted and the Hb values at admission, before and after the transfusion, together with the respective date and time. Comparisons analyses were made using the classical statistical tests. The Hb value before the transfusion is considered as the trigger for transfusion decision by the physician(s) in charge of the patients. Results: On a total of n = 501 episodes, n = 497 were evaluable for completeness of data. The corresponding number of packed RBCs represents the 2% of all the packed RBCs transfused at our Hospital in one year (n = 22170 in 2018). Median Hb was 10.70 (range: 6.30–16.70), 8.60 (range:3.00–15.10) and 10.30 (range: 5.00–16.30) at admission, before and after transfusion, respectively. Analyzing separately by unit, we observed that the transfusion trigger was higher in Cardiac Surgery, Vascular Surgery and Intensive Care Units, with median values of 9.50, 8.75 and 8.70 respectively. Conversely, transfusion trigger was comparable among the other surgical units (including Orthopedics) and the medical ones: Hb median values were 8.20, 8.20 and 8.30 respectively. Cardiology showed a slightly higher trigger: 8.65 when compared with the other non‐surgical units. Summary/Conclusion: The present analysis, accounting for « only » the 2% of the total transfusion burden at our Hospital in 2018, allows for a satisfactory definition of the transfusion trigger across the multiple medical and surgical units as well as the confirmation of the expected post‐transfusion Hb values. Our analysis model supports the feasibility of such an approach as a potential audit instrument and intervention policies in the area.
SAT0472 THE CONTRIBUTION OF MRI IN THE DIAGNOSIS OF INFECTIOUS SPONDYLODISCITIS
Authors: Rawdha Tekaya, Khaoula Zouaoui, Aicha Ben Tekaya, Lobna Ben Ammar, Olfa Saidane, Ines Mahmoud, Leila Abdelmoula
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Infectious spondylodiscitis is a diagnostic and therapeutic emergency, and if there is any doubt, an MRI should be performed to support the diagnosis. <h3>Objectives:</h3> The aim of our study is to highlight the role of MRI in the diagnosis of infectious spondylodiscitis. <h3>Methods:</h3> This is a 20-year retrospective study (1999-2019) performed at a rheumatology department, collecting cases of infectious spondylodiscitis. We have identified the epidemiological, clinical, and radiological characteristics. <h3>Results:</h3> Our study included 106 patients, 57 men and 49 women. The average age was 55 [16; 86]. Mean disease duration averaged 4.54 months [0.23; 24]. All patients had spinal pain: lumbar in 65.09% of cases, dorsal in 17% of cases and cervical in 6% of cases. Standard X-rays showed abnormalities suggestive of spondylodiscitis in 88.67% of cases. Magnetic resonance imaging was then performed in 76.41% patients and was pathological in all cases. The abnormalities found were paravertebral abscess in 23.58% of cases, epiduritis in 10.37% of cases and association of abscess and epiduritis in 32.07% of cases. The rest of the abnormalities noted were vertebral osteolysis (8.49%), spinal cord compression (9.43%) abnormalities of the intervertebral disc with narrowing and/or signal modification (4%). The abnormalities were monofocal in 82.07% of cases and bifocal in 13.2% of cases. 78.57% of bifocal lesions were objectified in tuberculous spondylodiscitis. 82.07% of the spinal injuries were single-stage and 15.09% were bi-staged. 75% of these were of tuberculous origin. There were 2.83% of spondylodiscites up to 3 stages and all were tuberculous. <h3>Conclusion:</h3> MRI is a great diagnostic aid during infectious spondylodiscitis. It also allows to orient towards the etiological diagnosis. <h3>Disclosure of Interests:</h3> None declared
Tolerability and toxicity of adjuvant cisplatin and gemcitabine for non-small cell lung cancer.
Authors: Xiao Li, Fan Yang, Guanchao Jiang, Jun Wang
Journal: Journal of Clinical Oncology (2012)

e17504 Background: The combination of cisplatin and vinorelbine is the evidence supported regimen for adjuvant chemotherapy of non-small cell lung cancer (NSCLC). But this doublet has considerable toxicity and unfavorable tolerability, and resulted in poor compliance. Cisplatin and gemcitabine regimen is one of the most active and well tolerated regimens against advanced NSCLC, but its toxicity and tolerability have not been adequately evaluated in the adjuvant setting. Methods: From a lung cancer database we retrospectively reviewed NSCLC patients receiving adjuvant chemotherapy of cisplatin (75 mg/m 2 ) and gemcitabine (1250 mg/m 2 ) between January 2005 and December 2011. Postoperative demographics, compliance to adjuvant therapy and toxicity were retrieved from medical records. Results: A total of 132 patients met the criteria and included in the study, 96 were males (72.7%)and 36 females (27.3%). Median age was 60.5 years (range, 29-75 years), and 41.7% patients were ≥65 years old. Overall, 68.2% received all four planned cycles, and cumulative dose delivered for gemcitabine was 8333 mg (83.3% planned) and cisplatin 248 mg (82.7% planned). There were no treatment-related deaths. Grade 3/4 neutropenia developed in 47 (35.6%) patients and was the predominant hematologic toxicity. Common grade 3/4 non-hematologic toxicities were nausea/vomiting (22.0%), infection (12.3%), and febrile neutropenia (11.4%). Conclusions: Cisplatin and gemcitabine are feasible in the adjuvant setting with favorable toxicity profile and superior tolerability compared with published data of cisplatin and vinorelbine.
Gadolinium-Free Cardiovascular Magnetic Resonance Stress T1 Mapping in Patients With Chronic Kidney Disease
Authors: Ranjit Shah, Karthigesh Sree Raman, Angela Walls, Richard J. Woodman, Randall Faull, Jonathan M. Gleadle, Joseph B. Selvanayagam
Journal: JACC. Cardiovascular imaging (2019)
Interventional Pharmacoeconomics—A New Discipline for a Cost-Constrained Environment
Authors: Mark J. Ratain, Daniel A. Goldstein, Allen S. Lichter
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
Effects of a Mediterranean Eating Plan on the Need for Glucose-Lowering Medications in Participants With Type 2 Diabetes: A Subgroup Analysis of the PREDIMED Trial
Authors: F. Javier Basterra-Gortari, Miguel Ruiz-Canela, Miguel A. Martínez-González, Nancy Babio, José V. Sorlí, Montserrat Fito, Emilio Ros, Enrique Gómez-Gracia, Miquel Fiol, José Lapetra, Ramón Estruch, Luis Serra-Majem, Xavier Pinto, José I. González, Mónica Bulló, Olga Castañer, Ángel Alonso-Gómez, Luis Forga, Fernando Arós
Journal: Diabetes Care (2019)

To examine the effects of two Mediterranean eating plans (Med-EatPlans) versus a low-fat eating plan on the need for glucose-lowering medications.From the Prevención con Dieta Mediterránea (PREDIMED) trial, we selected 3,230 participants with type 2 diabetes at baseline. These participants were randomly assigned to one of three eating plans: Med-EatPlan supplemented with extra-virgin olive oil (EVOO), Med-EatPlan supplemented with mixed nuts, or a low-fat eating plan (control). In a subgroup (15%), the allocation was done in small clusters instead of using individual randomization, and the clustering effect was taken into account in the statistical analysis. In multivariable time-to-event survival models, we assessed two outcomes: 1) introduction of the first glucose-lowering medication (oral or injectable) among participants on lifestyle management at enrollment and 2) insulin initiation.After a median follow-up of 3.2 years, in multivariable analyses adjusting for baseline characteristics and propensity scores, the hazard ratios (HRs) of starting a first glucose-lowering medication were 0.78 (95% CI 0.62-0.98) for Med-EatPlan + EVOO and 0.89 (0.71-1.12) for Med-EatPlan + nuts, compared with the control eating plan. After a median follow-up of 5.1 years, the adjusted HRs of starting insulin treatment were 0.87 (0.68-1.11) for Med-EatPlan + EVOO and 0.89 (0.69-1.14) for Med-EatPlan + nuts compared with the control eating plan.Among participants with type 2 diabetes, a Med-EatPlan + EVOO may delay the introduction of new-onset glucose-lowering medications. The Med-EatPlan did not result in a significantly lower need for insulin.
Drug expert is rejected from advisory committee for criticising government
Authors: Elisabeth Mahase
Journal: BMJ (2019)

An expert on drug policy has been disallowed from joining the Advisory Council on the Misuse of Drugs because of criticisms she made of the government’s position on drug consumption rooms.

Niamh Eastwood, executive director at Release, an independent body that provides expertise on drugs and drug law, had been cleared to join the council by the Home Office’s advisory assessment panel but was later rejected after her social media activity was vetted.

Eastwood had previously used Twitter to express negative views of the government’s drug policy, including a post saying that the government had misrepresented the evidence in relation …
Differential gene expression analysis tools exhibit substandard performance for long non-coding RNA-sequencing data
Authors: Alemu Takele Assefa, Katrijn De Paepe, Celine Everaert, Pieter Mestdagh, Olivier Thas, Jo Vandesompele
Journal: Genome biology (2018)

Long non-coding RNAs (lncRNAs) are typically expressed at low levels and are inherently highly variable. This is a fundamental challenge for differential expression (DE) analysis. In this study, the performance of 25 pipelines for testing DE in RNA-seq data is comprehensively evaluated, with a particular focus on lncRNAs and low-abundance mRNAs. Fifteen performance metrics are used to evaluate DE tools and normalization methods using simulations and analyses of six diverse RNA-seq datasets. Gene expression data are simulated using non-parametric procedures in such a way that realistic levels of expression and variability are preserved in the simulated data. Throughout the assessment, results for mRNA and lncRNA were tracked separately. All the pipelines exhibit inferior performance for lncRNAs compared to mRNAs across all simulated scenarios and benchmark RNA-seq datasets. The substandard performance of DE tools for lncRNAs applies also to low-abundance mRNAs. No single tool uniformly outperformed the others. Variability, number of samples, and fraction of DE genes markedly influenced DE tool performance. Overall, linear modeling with empirical Bayes moderation (limma) and a non-parametric approach (SAMSeq) showed good control of the false discovery rate and reasonable sensitivity. Of note, for achieving a sensitivity of at least 50%, more than 80 samples are required when studying expression levels in realistic settings such as in clinical cancer research. About half of the methods showed a substantial excess of false discoveries, making these methods unreliable for DE analysis and jeopardizing reproducible science. The detailed results of our study can be consulted through a user-friendly web application, giving guidance on selection of the optimal DE tool ( http://statapps.ugent.be/tools/AppDGE/ ).