tbuckley/cabot-search huggingface dataset:
Calprotectin is not independent from baseline erosion in predicting radiological progression in early rheumatoid arthritis. Comment on ‘Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis’ by Jonsson<i>et al</i>
Authors: Maxime Chevreau, Marie-Hélène Paclet, Xavier Romand, Jean-Louis Quesada, Olivier Vittecoq, Philippe Dieudé, Bertrand Toussaint, Philippe Gaudin, Athan Baillet
Journal: Annals of the Rheumatic Diseases (2018)

We have read with great interest the article by Jonsson et al that was recently published online in ARD ,1 which suggested that calprotectin, also known as S100A8/S100A9 heterodimer, was associated with radiographic progression in early rheumatoid arthritis (RA). Calprotectin correlates significantly with inflammatory markers and disease activity score.2 Besides correlations between baseline calprotectin levels, Clinical Disease Activity Index and ultrasonography power Doppler, the authors showed that baseline calprotectin levels correlated with van der Heijde modified Sharp score (SHS) progression (defined as an increase ≥1 unit/year from 0 to 24 months), independently of age, gender, Clinical Disease Activity Index, erythrocyte sedimentation rate (ESR), C reactive protein (CRP) levels and rheumatoid factor positivity.1 

We analysed the initial serum calprotectin among patients with early RA fulfilling American College of Rheumatology/European League Against Rheumatism 2010 of the French observational cohort Etude et Suivi des POlyarthrites Indifferenciees Recentes (ESPOIR). Calprotectin serum concentrations were assessed according to manufacturer method (Hycult, Frontstraat, Netherlands; …
Infusion Parameters and Adverse Events in Patients With Primary Immunodeficiency Diseases Who Switched to Subcutaneous Human Immune Globulin 20% (Ig20Gly) From Intravenous or Subcutaneous Immune Globulin
Authors: Iftikhar Hussain, Kenneth Paris, Amy Darter, Lisa J. Kobrynski, Todd Berner, Barbara McCoy, Ping Wang, Christopher J. Rabbat, Leman Yel
Journal: Journal of Allergy and Clinical Immunology (2018)
Hypersensitivity to paracetamol: placebo effect or overdiagnosis?
Authors: Andressa Zanandréa, Cláudia Castilho Mouco, João Paulo de Assis, Gabriella Melo Fontes Silva Dias, Raisa Borges Castro, Rebeca M. Brugnolli, Jorge Kalil, Antonio Abilio Motta, Pedro Giavina-Bianchi, Marcelo V. Aun
Journal: Journal of Allergy and Clinical Immunology (2018)
Visualizing T-cell fate: tolerance or priming
Authors: Karen Honey
Journal: Nature reviews. Immunology (2005)

Whether the characteristics of a dendritic cell (DC)-CD4 + T-cell interaction determine whether the CD4 + T cell is primed or tolerized remains an open question.However, new insight into this is provided by two groups who have shown in situ that there are only subtle differences in the behaviour of CD4 + T cells after antigen encounter under conditions that result in priming or tolerization.Previous two-photon microscopy studies that visualized T cells interacting with antigen-loaded DCs in situ indicated that, under priming conditions, antigen-specific T cells form stable contacts with DCs, whereas under tolerizing conditions, these stable contacts do not form.This has led to the hypothesis that the stability of the DC-T-cell interaction determines whether T cells are tolerized or primed. Because this hypothesis remains controversial, both groups set out to visually compare CD4 + T-cell priming and tolerance induction in situ.To deliver antigen to DCs in vivo, Shakhar et al. used a fusion protein consisting of a DC-specific antibody fused to the ovalbumin (OVA) peptide that is recognized by T cells expressing the OT-II T-cell receptor (TCR).Antigen was delivered alone or in combination with a CD40-specific antibody to create tolerizing or priming conditions, respectively.T cells expressing both the OT-II TCR and enhanced green fluorescent protein (EGFP) were transferred to the immunized animals, and the behaviour of the cells in the lymph nodes was tracked intravitally.Enhanced cyan fluorescent protein (ECFP)-expressing, antigen non-specific CD4 + T cells were co-transferred with the EGFP + OT-II TCR + T cells to distinguish antigen-specific and non-specific behaviour.During the first 6 hours of imaging, under both tolerizing and priming conditions, EGFP + OT-II TCR + T cells moved more slowly than the antigen non-specific ECFP + CD4 + T cells.In addition, a large proportion of the EGFP + OT-II TCR + T cells were immobile, spending more time arrested than the control ECFP + CD4 + T cells.The only differences between tolerizing and priming conditions were observed between 6 and 12 hours, when the EGFP + OT-II TCR + T cells regained speed more quickly under tolerizing conditions.Subsequently, between 12 and 18 hours, there was again little difference in the speed of the cells and in the amount of time spent arrested between EGFP + OT-II TCR + T cells and control ECFP + CD4 + T cells under either tolerizing or priming conditions.By contrast, Zinselmeyer et al. induced priming or tolerance by oral administration of OVA in the presence or absence of cholera-toxin adjuvant, and they imaged mucosal and systemic lymph
Subcutaneous Delivery of Daratumumab in Patients (pts) with Relapsed or Refractory Multiple Myeloma (RRMM): Pavo, an Open-Label, Multicenter, Dose Escalation Phase 1b Study
Authors: Ajai Chari, Hareth Nahi, Maria-Victoria Mateos, Henk M. Lokhorst, Jonathan L. Kaufman, Philippe Moreau, Albert Oriol, Torben Plesner, Lotfi Benboubker, Peter Hellemans, Tara Masterson, Pamela L Clemens, Kevin Liu, Jesus F. San-Miguel, Saad Z Usmani
Journal: Blood (2017)
CHRONIC URTICARIA IN CHILDREN: ARE THERE DIFFERENCES IN COMPARISON WITH ADULTS?
Authors: Pamela P. Silva, Lais Gomes Japiassú, Patrícia Guerzet Ayres Bastos, Luis Felipe C. Ensina, Ines Cristina Camelo Nunes, Dirceu Sole, Barbara Martins de Aquino, Chayanne Andrade de Araújo, Alex Eustáquio de Lacerda, Marina Medeiros Caputo
Journal: Journal of Allergy and Clinical Immunology (2018)
Lenalidomide, Bortezomib, and Dexamethasone (RVD) As Induction Therapy in Newly Diagnosed Multiple Myeloma (MM)
Authors: Nisha Joseph, Dhwani Almaula, Charise Gleason, Leonard Heffner, Lawrence H. Boise, Jonathan L. Kaufman, Sagar Lonial, Ajay Nooka
Journal: Blood (2017)
Abstract 20280: Impact of the Cholesteryl Ester Transfer Protein Inhibitor Evacetrapib on Cholesterol Efflux Capacity in High Risk Patients Within the ACCELERATE Trial
Authors: Giacomo Ruotolo, Michael A Lincoff, Steven E Nissen, Venugopal Menon, Jeffrey S Riesmeyer, Lauren Beacham, Ellen McErlean, Daniel J Rader, Stephen J Nicholls
Journal: Circulation (2016)

Background: The cholesteryl ester transfer protein (CETP) inhibitor, evacetrapib (Eva), did not reduce cardiovascular events in the ACCELERATE trial when added to high intensity statin despite favo...
Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis
Authors: Milka Koupenova, Lauren Clancy, Heather A. Corkrey, Jane E. Freedman
Journal: Circulation Research (2018)

Platelets, non-nucleated blood components first described over 130 years ago, are recognized as the primary cell regulating hemostasis and thrombosis. The vascular importance of platelets has been attributed to their essential role in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism. Increasing knowledge on the platelets' role in the vasculature has led to many advances in understanding not only how platelets interact with the vessel wall but also how they convey changes in the environment to other circulating cells. In addition to their well-described hemostatic function, platelets are active participants in the immune response to microbial organisms and foreign substances. Although incompletely understood, the immune role of platelets is a delicate balance between its pathogenic response and its regulation of thrombotic and hemostatic functions. Platelets mediate complex vascular homeostasis via specific receptors and granule release, RNA transfer, and mitochondrial secretion that subsequently regulates hemostasis and thrombosis, infection, and innate and adaptive immunity.
Early Detection of Scoliosis—What the USPSTF “I” Means for Us
Authors: M. Timothy Hresko, Richard M. Schwend, Richard A. Hostin
Journal: JAMA Pediatrics (2018)

John Dunn, MD, MPH; Nora B. Henrikson, PhD, MPH; Caitlin C. Morrison, MPH; Paula R. Blasi, MPH; Matt Nguyen, MPH; Jennifer S. Lin, MD, MCR
Refrigerated Stability of Diluted Cisatracurium, Rocuronium, and Vencuronium for Skin Testing After Perioperative Anaphylaxis
Authors: Kristen G. Dinsmore, Bethany Campbell, Timothy Archibald, Gregory Mosier, Stacy Brown, Alexei Gonzalez-Estrada
Journal: Journal of Allergy and Clinical Immunology (2018)
A Comparison of Clinical Manifestations between Childhood and Adult Onset Shrimp Allergy
Authors: Jintana Chataroopwijit, Pantipa Chatchatee, Pornphan Paurika, Jaichat Mekaroonkamol, Jarungchit Ngamphaiboon, Narissara Suratannon
Journal: Journal of Allergy and Clinical Immunology (2018)
Decision making in breast cancer risk reduction
Authors: Lara C. Pullen
Journal: CA A Cancer Journal for Clinicians (2018)

Key Points The DMP‐1 study examined women in the United States who were counseled regarding the use of SERMs as part of their regular care. Patient perceptions regarding drug‐based therapy played an important role in the choice of therapy. The findings suggest that HCPs should not only present medical information, but also communicate with patients regarding their beliefs and experiences.
Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Authors: David S. Siegel, Meletios A. Dimopoulos, Heinz Ludwig, Thierry Facon, Hartmut Goldschmidt, Andrzej Jakubowiak, Jesus San-Miguel, Mihaela Obreja, Julie Blaedel, A. Keith Stewart
Journal: Journal of Clinical Oncology (2018)

Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity. After 18 cycles, all patients received Rd only. Progression-free survival was the primary end point; OS was a key secondary end point. OS was compared between treatment arms using a stratified log-rank test. Results Median OS was 48.3 months (95% CI, 42.4 to 52.8 months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it was 6.5 months longer for KRd versus Rd among patients receiving ≥ two prior lines of therapy. Rates of treatment discontinuation because of adverse events (AEs) were 19.9% (KRd) and 21.5% (Rd). Grade ≥ 3 AE rates were 87.0% (KRd) and 83.3% (Rd). Selected grade ≥ 3 AEs of interest (grouped terms; KRd v Rd) included acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%), ischemic heart disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic thrombocytopenia (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%). Conclusion KRd demonstrated a statistically significant and clinically meaningful reduction in the risk of death versus Rd, improving survival by 7.9 months. The KRd efficacy advantage is most pronounced at first relapse.
Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett’s esophagus
Authors: Helen R. Moinova, Thomas LaFramboise, James D. Lutterbaugh, Apoorva Krishna Chandar, John Dumot, Ashley Faulx, Wendy Brock, Omar De la Cruz Cabrera, Kishore Guda, Jill S. Barnholtz-Sloan, Prasad G. Iyer, Marcia I. Canto, Jean S. Wang, Nicholas J. Shaheen, Prashanti N. Thota, Joseph E. Willis, Amitabh Chak, Sanford D. Markowitz
Journal: Science Translational Medicine (2018)

We report a biomarker-based non-endoscopic method for detecting Barrett's esophagus (BE) based on detecting methylated DNAs retrieved via a swallowable balloon-based esophageal sampling device. BE is the precursor of, and a major recognized risk factor for, developing esophageal adenocarcinoma. Endoscopy, the current standard for BE detection, is not cost-effective for population screening. We performed genome-wide screening to ascertain regions targeted for recurrent aberrant cytosine methylation in BE, identifying high-frequency methylation within the CCNA1 locus. We tested CCNA1 DNA methylation as a BE biomarker in cytology brushings of the distal esophagus from 173 individuals with or without BE. CCNA1 DNA methylation demonstrated an area under the curve of 0.95 for discriminating BE-related metaplasia and neoplasia cases versus normal individuals, performing identically to methylation of VIM DNA, an established BE biomarker. When combined, the resulting two biomarker panel was 95% sensitive and 91% specific. These results were replicated in an independent validation cohort of 149 individuals who were assayed using the same cutoff values for test positivity established in the training population. To progress toward non-endoscopic esophageal screening, we engineered a well-tolerated, swallowable, encapsulated balloon device able to selectively sample the distal esophagus within 5 min. In balloon samples from 86 individuals, tests of CCNA1 plus VIM DNA methylation detected BE metaplasia with 90.3% sensitivity and 91.7% specificity. Combining the balloon sampling device with molecular assays of CCNA1 plus VIM DNA methylation enables an efficient, well-tolerated, sensitive, and specific method of screening at-risk populations for BE.
Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice
Authors: I. Soria, J. López‐Relaño, M. Viñuela, J.‐I. Tudela, A. Angelina, C. Benito‐Villalvilla, C. M. Díez‐Rivero, B. Cases, A. I. Manzano, E. Fernández‐Caldas, M. Casanovas, O. Palomares, J. L. Subiza
Journal: Allergy (2018)

Abstract Background Polymerized allergoids coupled to nonoxidized mannan ( PM ‐allergoids) may represent novel vaccines targeting dendritic cells ( DC s). PM ‐allergoids are better captured by DC s than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM ‐allergoids administered sublingually in comparison with native allergens. Methods Three immunization protocols (4‐8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA . Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes ( LN s). Allergen uptake was measured by flow cytometry in myeloid sublingual cells. Results A quick antibody response and higher IgG2a/IgE ratio were observed with PM ‐allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LN s and spleen cells assayed in vitro. This was accompanied by a higher IFN γ/ IL ‐4 ratio with a quick IL ‐10 production by submandibular LN cells. An increase in CD 4 + CD 25 high FOXP 3 + Treg cells was detected in LN s and spleen of mice treated with PM ‐allergoids. These allergoids were better captured than native allergens by antigen‐presenting ( CD 45 + MHC ‐ II + ) cells obtained from the sublingual mucosa, including DC s ( CD 11b + ) and macrophages ( CD 64 + ). Importantly, all the differential effects induced by PM ‐allergoids were abolished when using oxidized instead of nonoxidized PM ‐allergoids. Conclusion Our results demonstrate for the first time that PM ‐allergoids administered through the sublingual route promote the generation of Th1 and FOXP 3 + Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen‐presenting cells.
Is selective 5-HT 1F receptor agonism an entity apart from that of the triptans in antimigraine therapy?
Authors: Eloísa Rubio-Beltrán, Alejandro Labastida-Ramírez, Carlos M. Villalón, Antoinette MaassenVanDenBrink
Journal: Pharmacology & Therapeutics (2018)

Migraine is a neurovascular disorder that involves activation of the trigeminovascular system and cranial vasodilation mediated by release of calcitonin gene-related peptide (CGRP). The gold standard for acute migraine treatment are the triptans, 5-HT1B/1D/(1F) receptor agonists. Their actions are thought to be mediated through activation of: (i) 5-HT1B receptors in cranial blood vessels with subsequent cranial vasoconstriction; (ii) prejunctional 5-HT1D receptors on trigeminal fibers that inhibit trigeminal CGRP release; and (iii) 5-HT1B/1D/1F receptors in central nervous system involved in (anti)nociceptive modulation. Unfortunately, coronary arteries also express 5-HT1B receptors whose activation would produce coronary vasoconstriction; hence, triptans are contraindicated in patients with cardiovascular disease. In addition, since migraineurs have an increased cardiovascular risk, it is important to develop antimigraine drugs devoid of vascular (side) effects. Ditans, here defined as selective 5-HT1F receptor agonists, were developed on the basis that most of the triptans activate trigeminal 5-HT1F receptors, which may explain part of the triptans' antimigraine action. Amongst the ditans, lasmiditan: (i) fails to constrict human coronary arteries; and (ii) is effective for the acute treatment of migraine in preliminary Phase III clinical trials. Admittedly, the exact site of action is still unknown, but lasmiditan possess a high lipophilicity, which suggests a direct action on the central descending antinociceptive pathways. Furthermore, since 5-HT1F receptors are located on trigeminal fibers, they could modulate CGRP release. This review will be particularly focussed on the similarities and differences between the triptans and the ditans, their proposed sites of action, side effects and their cardiovascular risk profile.
Inorganic Nitrite Selectively Dilates Epicardial Coronary Arteries
Authors: Kevin O’Gallagher, Faisal Khan, Sami A. Omar, Sundeep Kalra, Edward Danson, Ana R. Cabaco, Katherine Martin, Narbeh Melikian, Ajay M. Shah, Andrew J. Webb
Journal: Journal of the American College of Cardiology (2018)
The carbon footprint of Australian health care
Authors: Arunima Malik, Manfred Lenzen, Scott McAlister, Forbes McGain
Journal: The Lancet Planetary Health (2018)

BackgroundCarbon footprints stemming from health care have been found to be variable, from 3% of the total national CO2 equivalent (CO2e) emissions in England to 10% of the national CO2e emissions in the USA. We aimed to measure the carbon footprint of Australia's health-care system.MethodsWe did an observational economic input–output lifecycle assessment of Australia's health-care system. All expenditure data were obtained from the 15 sectors of the Australian Institute of Health and Welfare for the financial year 2014–15. The Australian Industrial Ecology Virtual Laboratory (IELab) data were used to obtain CO2e emissions per AUS$ spent on health care.FindingsIn 2014–15 Australia spent $161·6 billion on health care that led to CO2e emissions of about 35 772 (68% CI 25 398–46 146) kilotonnes. Australia's total CO2e emissions in 2014–15 were 494 930 kilotonnes, thus health care represented 35 772 (7%) of 494 930 kilotonnes total CO2e emissions in Australia. The five most important sectors within health care in decreasing order of total CO2e emissions were: public hospitals (12 295 [34%] of 35 772 kilotonnes CO2e), private hospitals (3635 kilotonnes [10%]), other medications (3347 kilotonnes [9%]), benefit-paid drugs (3257 kilotonnes [9%]), and capital expenditure for buildings (2776 kilotonnes [8%]).InterpretationThe carbon footprint attributed to health care was 7% of Australia's total; with hospitals and pharmaceuticals the major contributors. We quantified Australian carbon footprint attributed to health care and identified health-care sectors that could be ameliorated. Our results suggest the need for carbon-efficient procedures, including greater public health measures, to lower the impact of health-care services on the environment.FundingNone.
Abstract 17082: Translation From Highly Multiplexed Biomarker Discovery to a Targeted Protein Panel to Stratify Cardiovascular Risk in Patients With Coronary Heart Disease
Authors: Robert K DeLisle, Peter Ganz, Evaldas Katilius, Shintaro Kato, Rachel Ostroff, David Sterling, Stephen Williams
Journal: Circulation (2016)

Introduction: Failure to translate biomarkers from research publication to practical clinical measurements is well-recognized. The objective of this study was to transition from a research discover...
US is the most dangerous wealthy nation for a child to be born into, study concludes
Authors: Michael McCarthy
Journal: BMJ (2018)

High poverty rates, poor educational outcomes, and a weak social safety net have made the US the “most dangerous of wealthy nations for a child to be born into,” a new study concludes.1

In the study, appearing in the January issue of Health Affairs , researchers looked at childhood mortality, comparing trends for the US with 19 other wealthy democracies for children aged from 0 to 19 years from 1961 to 2010.

The comparator nations were Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, …
Patient Selection for Transarterial Chemoembolization in Hepatocellular Carcinoma: Importance of Benefit/Risk Assessment
Authors: Fabio Piscaglia, Sadahisa Ogasawara
Journal: Liver Cancer (2018)

Background: Liver cancer is the second most common cause of cancer-related death, with hepatocellular carcinoma (HCC) accounting for most primary liver cancers and most commonly arising from a history of advanced chronic liver disease. Among the available therapies, transarterial chemoembolization (TACE) is the most widely utilized and is considered the first-line treatment recommended for patients staged as intermediate HCC (Barcelona Clinic Liver Cancer stage B). If applied correctly, TACE can produce survival benefits without adversely affecting hepatic functional reserve. Summary: The aim of this nonsystematic review is to evaluate the evidence supporting TACE, with a special interest in intermediate HCC, for which this treatment is recommended in first line. However, intermediate HCC represents a broad and heterogeneous group of patients, not all of whom will benefit from TACE. This review highlights the importance of appropriate patient selection for initial TACE and for retreatment. It also evaluates evidence for the treatment of patients who become refractory to TACE. Some patients may, in fact, benefit from early switch (i.e., after 1 or 2 TACE treatments) to systemic therapies rather than continuing retreatments with TACE in order to preserve liver function, thus allowing sequential first- and second-line drug therapies. Key Messages: Careful assessment of an individual patient's benefit/risk ratio is recommended before any TACE session is considered to ensure optimal long-term outcomes in intermediate HCC.
Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention
Authors: Chun Loong Ho, Hui Qing Tan, Koon Jiew Chua, Aram Kang, Kiat Hon Lim, Khoon Lin Ling, Wen Shan Yew, Yung Seng Lee, Jean Paul Thiery, Matthew Wook Chang
Journal: Nature Biomedical Engineering (2018)