tbuckley/cabot-search huggingface dataset:
Evaluation and Management of Penicillin Allergy
Authors: Erica S. Shenoy, Eric Macy, Theresa Rowe, Kimberly G. Blumenthal
Journal: JAMA (2019)

<h3>Importance</h3> β-Lactam antibiotics are among the safest and most effective antibiotics. Many patients report allergies to these drugs that limit their use, resulting in the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance and adverse events. <h3>Observations</h3> Approximately 10% of the US population has reported allergies to the β-lactam agent penicillin, with higher rates reported by older and hospitalized patients. Although many patients report that they are allergic to penicillin, clinically significant IgE-mediated or T lymphocyte–mediated penicillin hypersensitivity is uncommon (&lt;5%). Currently, the rate of IgE-mediated penicillin allergies is decreasing, potentially due to a decreased use of parenteral penicillins, and because severe anaphylactic reactions to oral amoxicillin are rare. IgE-mediated penicillin allergy wanes over time, with 80% of patients becoming tolerant after a decade. Cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, less than the 8% reported previously. Some patients have a medical history that suggests they are at a low risk for developing an allergic reaction to penicillin. Low-risk histories include patients having isolated nonallergic symptoms, such as gastrointestinal symptoms, or patients solely with a family history of a penicillin allergy, symptoms of pruritus without rash, or remote (&gt;10 years) unknown reactions without features suggestive of an IgE-mediated reaction. A moderate-risk history includes urticaria or other pruritic rashes and reactions with features of IgE-mediated reactions. A high-risk history includes patients who have had anaphylaxis, positive penicillin skin testing, recurrent penicillin reactions, or hypersensitivities to multiple β-lactam antibiotics. The goals of antimicrobial stewardship are undermined when reported allergy to penicillin leads to the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance, including increased risk of methicillin-resistant<i>Staphylococcus aureus</i>and vancomycin-resistant<i>Enterococcus</i>. Broad-spectrum antimicrobial agents also increase the risk of developing<i>Clostridium difficile </i>(also known as<i>Clostridioides difficile</i>) infection. Direct amoxicillin challenge is appropriate for patients with low-risk allergy histories. Moderate-risk patients can be evaluated with penicillin skin testing, which carries a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge. Clinicians performing penicillin allergy evaluation need to identify what methods are supported by their available resources. <h3>Conclusions and Relevance</h3> Many patients report they are allergic to penicillin but few have clinically significant reactions. Evaluation of penicillin allergy before deciding not to use penicillin or other β-lactam antibiotics is an important tool for antimicrobial stewardship.
Long Term Follow-up of the PRIMA Study: Half of Patients Receiving Rituximab Maintenance Remain Progression Free at 10 Years
Authors: Gilles Andre Salles, John Francis Seymour, Pierre Feugier, Fritz Offner, Armando Lopez-Guillermo, David Belada, Luc Xerri, Reda Bouabdallah, John Catalano, Pauline Brice, Corinne Haioun, Alejandro Martín, Lars Moller Pedersen, Alain Jacques Delmer, David Simpson, Sirpa Leppa, Pierre Soubeyran, Rene-Olivier Casasnovas, Tanin Intragumtornchai, Vincent Ribrag, Maria Gomes Silva, Emmanuelle Nicolas-Virelizier, Thomas Lister, Jane Estell, Gustavo Milone, Anne Sonet, Julie Assemat, Harald Zeuner, Bertrand Coiffier, Herve Tilly
Journal: Blood (2017)
Abstract 16019: Choosing Wisely: Number and Type of Acute Coronary Syndrome Symptom Clusters Vary by Analytic Method
Authors: Catherine J Ryan, Karen M Vuckovic, Lani Zimmerman, Susan Barnason, Bunny Pozehl, Lorna K Finnegan, Holli A DeVon
Journal: Circulation (2017)

Introduction/Objective: Patients with acute coronary syndrome (ACS) frequently experience multiple symptoms. A symptom cluster is the occurrence of two or more symptoms that are related. There are ...
THU0457 Interleukin-6 expression in inflamed and non-inflamed temporal arteries from patients with giant cell arteritis
Authors: N. Pipitone, F. Muratore, I. Tamagnini, A. Cavazza, L. Cimino, L. Boiardi, G. Restuccia, M. Bonacini, S. Croci, C. Salvarani
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To evaluate if interleukin-6 (IL-6) expression in the temporal artery biopsy (TAB) specimens may differentiate patients with giant cell arteritis (GCA) from those without. <h3>Methods</h3> 63 consecutive formalin-fixed, paraffin-embedded (FFPE) TABs performed between 2009 and 2012 from 32 patients with transmural biopsy-proven GCA, 8 patients with biopsy-negative GCA and 23 controls were retrieved. Demographic, clinical, and laboratory data at presentation and at each follow-up visit were collected. A pathologist reviewed all TABs. Immunohistochemistry was performed on 4 µm FFPE tissue sections with a 1:400 dilution of rabbit polyclonal anti-human IL-6 antibody (NOVUS Biologicals Littleton, Co.) for 60' at 37°. Slides of TAB specimens were independently assessed by five readers. IL-6 expression was graded as 0 (absent), 1 (mild), 2 (moderate) and 3 (marked). Inter-reader differences were resolved by consensus. Anti-IL6 staining was considered positive if staining was grade 2 or 3, since grade 1 was faint, sometimes difficult to differentiate from background, and showed the least degree of agreement between readers. <h3>Results</h3> TAB specimens from patients with biopsy-proven GCA, biopsy-negative GCA and controls were positive for anti-IL-6 staining in 59%, 13% and 48% of cases, respectively, the difference between biopsy-proven and biopsy-negative GCA patients being significant (p=0.04). In non-inflamed TABs, IL-6 was mainly expressed by mesenchymal cells in media and intima layers, while in inflamed TABs IL-6 was mainly expressed by mononuclear inflammatory infiltrating cells. IL-6 grade 2–3 expression was observed in all 6 patients with visual loss compared to 25 (43.9%) of 57 patients without (p=0.011). Blindness was recorded in 2 patients with biopsy-proven GCA and 4 controls (all with a final diagnosis of non-arteritic ischaemic optic neuropathy). No associations were found between IL-6 expression and demographic characteristics, GCA signs/symptoms, laboratory and histopathological TAB findings. However, there was a statistical trend (p=0.055) of increased frequency of the halo sign at temporal artery CDS in patients with IL-6 expression grade 2–3 compared to those with IL-6 expression grade 0–1. No significant differences for the expression of IL-6 were observed between patients with and without PMR (5/8%–62.5% - versus 6/15%–40% -, p=0.400) and between patients with isolated PMR and those with TAB positive GCA (62.5% vs 59%, p=1.000). <h3>Conclusions</h3> Our study provides evidence that IL-6 expression does not increase the sensitivity of TAB in patients with morphologically uninflamed arteries. A search for further markers that may increase the sensitivity of TAB is warranted. <h3>Disclosure of Interest</h3> None declared
THU0562 Evolution of serum calprotectin in patients with juvenile idiopathic arthritis in clinical practice
Authors: B. Magallares López, L. Martínez-Martínez, M.C. Hernandez-Lafuente, E. Moltó, Y. Alvaro, H. Park, I. Castellví, M. Millán, C. Díaz-Torné, P. Moya, A. Laiz, H. Corominas, J. Casademont, E. Carreras, C. Juarez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Serum Calprotectin (MPR8/MPR14) is a promising biomarker in the management of juvenile idiopathic arthritis (JIA), mainly as a predictor of flare, especially in treatment de-escalation <h3>Objectives</h3> To describe the evolution of serum Calprotectin in patients with JIA, their clinical evolution and its impact on therapeutic decisions <h3>Methods</h3> Demographic, clinical and inflammatory activity data (RCP and ESR) were retrospectively collected in patients with JIA of any subtype in whom serum Calprotectin had been determined at least once <h3>Results</h3> We present the data of 15 children, 7 with Oligoarticular subtype JIA, 1 Systemic, 3 Polyarticular, 1 Psoriasic and 3 Enthesitis Related Arthritis (ERA) The average age was 11 years, 66% female. The characteristics of each patient can be seen in table 1, together with the first determination of serum Calprotectin, CRP and ESR. It also shows the physiscan's decision, and the outcome, obtained from the assessment in the next visit Considering the cutoff point of serum Calprotectin in our sample of: 2.2 µg/mL (80% sensitivity and 69% specificity), 9 of 15 patients presented high values, 2 of them presented a flare (1 Oligo and 1 Poly), both had maintained the same treatment, because they were considered inactive. There were no flares in patients with negative Calprotectin The evolution of serum Calprotectin, together with the clinical decisions (based on clinical and analytical assessment) are described in table 1 In most of stable patients in whom serum calprotectin was high, it was decided not to lower treatment, and only in one case it was de-escalated. There were no flares in any of them <h3>Conclusions</h3> Serum Calprotectin is a useful biomarker in routine clinical practice, together with other markers such as CRP and ESR, and our clinical judgment, it helps us to make therapeutic decisions <h3>Disclosure of Interest</h3> None declared
Response by McCord et al to Letter Regarding Article, “Designing a Better Mousetrap: Reflections on the November 28, 2017, US Food and Drug Administration Meeting on Next-Generation “High-Sensitivity” Cardiac Troponin Assays to Diagnose Myocardial Infarction”
Authors: James McCord, L. Kristin Newby, Christopher R. deFilippi
Journal: Circulation (2019)
The psychomotor vigilance task: Role in the diagnosis of hepatic encephalopathy and relationship with driving ability
Authors: Chiara Formentin, Michele De Rui, Mirko Zoncapè, Silvia Ceccato, Lisa Zarantonello, Marco Senzolo, Patrizia Burra, Paolo Angeli, Piero Amodio, Sara Montagnese
Journal: Journal of Hepatology (2019)
AB0887 Jia patients with high disease activity have increased activity of both the ido and gtp-ch1 pathway, but decreased bh4 efficacy: consequences for fatigue and well-being
Authors: S. Korte, E. Albers, W. van den Bogaard, G. Korte-Bouws, S. de Roock, S. Vastert
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) patients suffer from an inflammatory condition, resulting in painful joints. In addition, JIA patients often report symptoms of sickness behaviour, including depressive symptoms and fatigue. Recent animal studies suggest that proinflammatory cytokines produce sickness behaviour by increasing the activity of indoleamine-2,3-dioxygenase (IDO) and guanosinetriphosphate-cyclohydrolase-1 (GTP-CH1). Here it is hypothesised that inflammation in JIA patients affects the enzymatic activity of IDO and GTP-CH1 and the co-factor BH4. These compounds play a crucial role in the metabolism of the neurotransmitters serotonin and dopamine. <h3>Objectives</h3> The aim of our study was to reveal whether inflammation affects BH4, IDO and GTP-CH1 (enzymatic) activity in JIA patients. <h3>Methods</h3> Serum samples were collected of twenty-four JIA patients. In these samples, the concentrations of tryptophan, kynurenine, tyrosine, neopterin and phenylalanine were measured. An HPLC method with electrochemical detection was developed to quantify tryptophan, kynurenine and tyrosine. Neopterin and phenylalanine were quantified by ELISA. Kyn/trp ratio was measured as an index of IDO activity, while Phen/Tyr ratio was measured as an index of BH4 activity. Neopterin concentrations were used as an indirect measure of GTP-CH1 activity. <h3>Results</h3> JIA patients with high disease activity showed higher levels of both neopterin and kynurenine, and a higher ratio of both Kyn/Trp and Phen/Tyr and lower tryptophan levels than clinically inactive patients. <h3>Conclusions</h3> Altogether, these data support our hypothesis that inflammation increases the enzymatic activity of both IDO and GTP-CH1 and decreases the efficacy of the co-factor BH4. Further animal studies are needed to investigate whether inflammation-induced changes in these enzymatic pathways and co-factor lower the levels of the brain neurotransmitters dopamine and serotonin, and consequently produce sickness behaviour and fatigue. <h3>Acknowledgements</h3> This study was financially supported by the focus area "Future Food Utrecht" of Utrecht University, The Netherlands. <h3>Disclosure of Interest</h3> None declared
Molecular Features of Primary Central Nervous System Lymphoma in a Large Tissue Microarray
Authors: Diego Villa, Graham W Slack, Muntadhar Al-Moosawi, Susana Ben-Neriah, Tamara Shenkier, Joseph M. Connors, Laurie H Sehn, Kerry J Savage, David W. Scott, Christian Steidl, Randy D. Gascoyne, King Tan
Journal: Blood (2018)
AB0134 Phosphorelated stat3 expression in peripheral blood mononuclear cells in rheumatoid arthritis
Authors: S. Perniola, F. Cacciapaglia, D. Natuzzi, R. Bizzoca, N. Lacarpia, F. Iannone
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The JAK-STAT pathway is mainly involved in the regulation of the expression of cytokines and growth factors; so it controls the proliferation, differentiation, migration and death of the cells of the immune system. In patients with RA, studies have shown increased activation of STAT3 with undergoes phosphorylated (pSTAT3), probably due to increased levels of cytokines such as IL-6, IL-11, IL-12. <h3>Objectives</h3> This study aims at investigating the level of expression of STAT3 and pSTAT3 in peripheral blood lymphomonocytes cells of patients with Rheumatoid Arthritis (RA), correlating them with disease activity (ESR, CRP, clinimetric tests). <h3>Methods</h3> Patients affected with RA, according to the 2010 EULAR/ACR classification criteria, were enrolled in this study. Exclusion criteria were: minority age, status of pregnancy or breastfeeding, concomitant any other autoimmune disease. At entry (new treatment with csDMARDs or biological drugs) ESR, CRP, DAS28-ESR, CDAI and peripheral venous blood sample were collected. The expression of STAT3 and pSTAT3 in lymphomonocytes cells, CD4 and CD14 cells were evaluated by flow-cytometry assay. The level of <i>STAT3</i> gene was studied by qPCR. Differences for continuous variables were evaluated using the Mann-Whitney test, while for categorical data the Kolmogorov-Smirnov test. Correlations were assessed using the Spearman test. <h3>Results</h3> Twenty RA patients were studied, comparing STAT3 and pSTAT3 levels with 9 seronegative arthritis patients (SA) and 8 healthy control (HC). While no difference in the expression of STAT3 levels between the 3 groups (in flow-cytometry and qPCR assays), pSTAT3 was higher in RA (9,5%) than in SA (2,74%) (p: 0.005) or HC (4,81%) (p: 0.04); between the 3 groups, pSTAT3 was differently expressed in CD4-lymphocytes and CD14-monocytes (figure 1). We also demonstrated a correlation between pSTAT3 level in CD14 +cells and ESR (p: 0.026; r: 0,4625). We found no correlation between pSTAT3 expression and Body Mass Index or disease duration. <h3>Conclusions</h3> In this study, STAT3 seems to be activated more in RA than SA or HC. Monocytes (as macrophage) and T-cells have important role in RA. Isomaki et al. demonstrated a correlation between IL-6 level and STAT3 activation so it might be suggested a possible role of pSTAT3 as a biomarker of disease activity. However, further studies are needed to explore the important role of JAK-STAT pathway in RA. <h3>References</h3> [1] Harris TJ, et al. Cutting Edge: An In Vivo Requirement for STAT3 Signaling in Th17 Development and Th17-Dependent Autoimmunity. J Immunol2007. [2] Nurieva R, et al. Generation of Inflammatory Helper T Cells STAT3 Regulates Cytokine-mediated. J. Biol. Chem. 2007. [3] Walker JG, Smith MD. The Jak-STAT Pathway in Rheumatoid Arthritis.Editorial of The Journal of Rheumatology 2005. <h3>Disclosure of Interest</h3> None declared
Long-Term Follow-Up After Closure of Patent Foramen Ovale in Patients With Cryptogenic Embolism
Authors: Jérôme Wintzer-Wehekind, Alberto Alperi, Christine Houde, Jean-Marc Côté, Lluis Asmarats, Mélanie Côté, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2019)
AB0807 Platelet indices as markers of inflammation in systemic sclerosis
Authors: S. Eldessouki Ibrahim, C. Morad
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is a connective tissue disease involving multiple organs with an unknown etiology. Platelet function may be associated with endothelial dysfunction and immune regulatory mechanisms. Recently, an increased tendency to platelet aggregation and enhanced platelet activation have been described in SSc patients, suggesting a role for platelets in the disease itself.<sup>1 2</sup> <h3>Objectives</h3> To evaluate platelet indices in systemic sclerosis (SSc) patients and identify their clinical significance as novel inflammatory biomarkers in correlation to markers of endothelial dysfunction: vascular endothelial growth factor (VEGF) and flow mediated dilatation (FMD). <h3>Methods</h3> Thirty-five SSc patients were enrolled in addition to thirty-five age and sex matched healthy volunteers as controls. All patients and controls underwent full medical history taking, thorough clinical examination, assessment of severity extent of skin sclerosis using the modified Rodnan skin score, erythrocyte sedimentation rate (ESR), C- reactive protein (CRP), complete blood count with special consideration to mean platelet volume (MPV), platelet distribution width and platelets count, assay for serum VEGF concentration, and brachial FMD assessment by colour duplex sonography. <h3>Results</h3> There was a highly significant decrease in the mean MPV in SSc patients compared to the controls (8.65±0.6 fl vs. 9.55±0.52 fl). There was a significant increase in the mean platelet count in SSc patients compared to controls (331.63±64.66 × 10<sup>3</sup>/ml vs. 297.80±44.48 × 10<sup>3</sup>/ml). In SSc patients, a significant negative correlation was found between the mean MPV and each of ESR, CRP and VEGF (r=−0.42,–0.368 and −0.55 respectively, p&lt;0.05); and a significant positive correlation was found between the mean MPV and mean FMD (r=0.378, p&lt;0.05). Linear regression test, showed an association between mean MPV and each of ESR and CRP (t=−3.312,–2.92 respectively, p&lt;0.05). <h3>Conclusions</h3> MPV levels could be an easily measurable parameter to reflect the inflammatory condition and disease activity in systemic sclerosis patients. <h3>References</h3> [1] da Silva IF, Teixeira A, Oliveira J, Almeida R, Vasconcelos C2017Jan27 [2] Manetti M The crowded crossroad to angiogenesis in systemic sclerosis: where is the key to the problem?Arthritis Res Ther2016;18:36 <h3>Disclosure of Interest</h3> None declared
Food in the Anthropocene: the EAT–Lancet Commission on healthy diets from sustainable food systems
Authors: Walter Willett, Johan Rockström, Brent Loken, Marco Springmann, Tim Lang, Sonja Vermeulen, Tara Garnett, David Tilman, Fabrice DeClerck, Amanda Wood, Malin Jonell, Michael Clark, Line J Gordon, Jessica Fanzo, Corinna Hawkes, Rami Zurayk, Juan A Rivera, Wim De Vries, Lindiwe Majele Sibanda, Ashkan Afshin, Abhishek Chaudhary, Mario Herrero, Rina Agustina, Francesco Branca, Anna Lartey, Shenggen Fan, Beatrice Crona, Elizabeth Fox, Victoria Bignet, Max Troell, Therese Lindahl, Sudhvir Singh, Sarah E Cornell, K Srinath Reddy, Sunita Narain, Sania Nishtar, Christopher J L Murray
Journal: The Lancet (2019)
Tumor mutational load predicts survival after immunotherapy across multiple cancer types
Authors: Robert M. Samstein, Chung-Han Lee, Alexander N. Shoushtari, Matthew D. Hellmann, Ronglai Shen, Yelena Y. Janjigian, David A. Barron, Ahmet Zehir, Emmet J. Jordan, Antonio Omuro, Thomas J. Kaley, Sviatoslav M. Kendall, Robert J. Motzer, A. Ari Hakimi, Martin H. Voss, Paul Russo, Jonathan Rosenberg, Gopa Iyer, Bernard H. Bochner, Dean F. Bajorin, Hikmat A. Al-Ahmadie, Jamie E. Chaft, Charles M. Rudin, Gregory J. Riely, Shrujal Baxi, Alan L. Ho, Richard J. Wong, David G. Pfister, Jedd D. Wolchok, Christopher A. Barker, Philip H. Gutin, Cameron W. Brennan, Viviane Tabar, Ingo K. Mellinghoff, Lisa M. DeAngelis, Charlotte E. Ariyan, Nancy Lee, William D. Tap, Mrinal M. Gounder, Sandra P. D’Angelo, Leonard Saltz, Zsofia K. Stadler, Howard I. Scher, Jose Baselga, Pedram Razavi, Christopher A. Klebanoff, Rona Yaeger, Neil H. Segal, Geoffrey Y. Ku, Ronald P. DeMatteo, Marc Ladanyi, Naiyer A. Rizvi, Michael F. Berger, Nadeem Riaz, David B. Solit, Timothy A. Chan, Luc G. T. Morris
Journal: Nature Genetics (2019)
SP0146 The link between inflammation and depression
Authors: N. Harrison
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Inflammation is increasingly implicated in the etiology of depression. Patients with idiopathic depression have been shown to express increased circulating pro-inflammatory cytokines and 30% of patients receiving chronic Interferon-alpha for the treatment of Hepatitis-C develop major depression. Recently, anti-inflammatory agents, including 'biologics' developed for rheumatoid arthritis, have shown potential efficacy for the treatment of idiopathic depression. However, the utility of these medications is highly variable emphasising the importance of identifying biomarkers that may predict treatment response. Interestingly, neuroimaging studies have recently demonstrated that increases in inflammation can rapidly alter brain function and microstructural integrity. Further, these acute changes in brain structure/function can additionally predict the later development of depressive response during sustained inflammatory challenge. For example, in patients with Hepatitis-C given Interferon-alpha over a prolonged period, acute changes in ventral striatal microstructure (observed within 4 hours of the first injection of Interferon) predict the magnitude of fatigue/motivational impairment experienced 4 weeks later while acute changes in amygdala processing of emotionally valenced stimuli predicts the magnitude of depressive symptoms. Conversely, inhibitors of Tumour Necrosis Factor (TNF) reduce amygdala reactivity to emotional stimuli, which correlate with improvement in mood. Together, these studies highlight the importance of inflammatory processes in depression and support on-going trials of anti-inflammatory agents in this common and functionally impairing disorder. <h3>Disclosure of Interest</h3> N. Harrison Grant/research support from: Janssen, Consultant for: GSK