tbuckley/cabot-search huggingface dataset:
Autoantibodies to Malondialdehyde–Acetaldehyde Are Detected Prior to Rheumatoid Arthritis Diagnosis and After Other Disease Specific Autoantibodies
Authors: Ted R. Mikuls, Jess Edison, Elizabeth Meeshaw, Harlan Sayles, Bryant R. England, Michael J. Duryee, Carlos D. Hunter, Lindsay B. Kelmenson, Laura Kay Moss, Marie L. Feser, Brandie Wagner, Mark C. Parish, Kevin D. Deane, Geoffrey M. Thiele
Journal: Arthritis & Rheumatology (2020)

Objective To examine serum autoantibodies to malondialdehyde–acetaldehyde (MAA) prior to rheumatoid arthritis (RA) diagnosis. Methods Concentrations of anti‐MAA antibody isotypes, anti–cyclic citrullinated peptide 2 (anti–CCP‐2), and IgM rheumatoid factor (IgM‐RF) were evaluated before and after RA diagnosis in samples from cases (n = 214) and controls (n = 210). The timing of elevations in autoantibody concentrations relative to RA diagnosis was explored using separate mixed models for each antibody and/or isotype. Associations between prediagnosis autoantibody concentrations in RA patients were examined using mixed effects linear regression models. Results Concentrations of IgG (log 2 difference 0.34) and IgA (log 2 difference 0.43) anti‐MAA antibodies in RA patients diverged from controls at 3.0 years and 2.3 years prior to diagnosis, respectively ( P &lt; 0.05 for both). There was no evidence of case–control divergence for IgM anti‐MAA antibody concentration. Anti–CCP‐2 and IgM‐RF concentrations diverged between RA patients and controls beginning at 17.6 years and 7.2 years prior to RA diagnosis, respectively. All 3 anti‐MAA antibody isotypes (IgA, IgM, and IgG) were significantly associated with anti–CCP‐2 antibody and RF concentrations prior to diagnosis (β = 0.22–0.27 for IgM‐RF; β = 0.44–0.93 for anti–CCP‐2) ( P &lt; 0.001). Conclusion IgG and IgA anti‐MAA autoantibodies are elevated prior to RA diagnosis but appear later in the preclinical course than anti–CCP‐2 or RF. These findings suggest that MAA formation and anti‐MAA immune responses could play a role in the transition from subclinical autoimmunity to clinically apparent arthritis.
Abstract 17230: Effectiveness of Catheter Directed Thrombolysis for Massive and Submassive Pulmonary Embolism Compared to Systemic Thrombolysis or No Thrombolysis
Authors: Abhinav C Krishnan, Dhruvil A Patel, Christina Reji, Mahir Elder, Vijaya A Kumar
Journal: Circulation (2019)

Introduction: Effective treatment strategies for pulmonary embolism (PE) presents a challenge for emergency medicine physicians. Three subtypes of PE’s exist, massive (MPE), sub-massive (SPE) or no...
Maintenance inhaler therapy preferences of patients with asthma or chronic obstructive pulmonary disease: a discrete choice experiment
Authors: Tommi Tervonen, Natalia Hawken, Nicola A Hanania, Fernando J Martinez, Sebastian Heidenreich, Ileen Gilbert
Journal: Thorax (2020)

Background A variety of maintenance inhaler therapies are available to treat asthma and COPD. Patient-centric treatment choices require understanding patient preferences for the alternative therapies. Methods A self-completed web-based discrete choice experiment was conducted to elicit patient preferences for inhaler device and medication attributes. Selection of attributes was informed by patient focus groups and literature review. Results The discrete choice experiment was completed by 810 patients with asthma and 1147 patients with COPD. Patients with asthma most valued decreasing the onset of action from 30 to 5 min, followed by reducing yearly exacerbations from 3 to 1. Patients with COPD most and equally valued decreasing the onset of action from 30 to 5 min and reducing yearly exacerbations from 3 to 1. Both patients with asthma and patients with COPD were willing to accept an additional exacerbation in exchange for a 15 min decrease in onset of action and a longer onset of action in exchange for a lower risk of adverse effects from inhaled corticosteroids. Patients with asthma and COPD valued once-daily over twice-daily dosing, pressurised inhalers over dry powder inhalers and non-capsule priming over single-use capsules, although these attributes were not valued as highly as faster onset of action or reduced exacerbations. Conclusions The most important maintenance inhaler attributes for patients with asthma and COPD were fast onset of symptom relief and a lower rate of exacerbations. Concerns about safety of inhaled corticosteroids and device convenience also affected patient preferences but were less important.
Lymphatic Vessels in Tumor Dissemination versus Immunotherapy
Authors: Kari Vaahtomeri, Kari Alitalo
Journal: Cancer Research (2020)

During the growth of various cancers, primary tumors can escape antitumor immune responses of their host and eventually disseminate into distant organs. Peritumoral lymphatic vessels connect the primary tumor to lymph nodes, facilitating tumor entry into lymph nodes, systemic circulation, and metastasis. Lymph node metastases that occur frequently provide sites of tumor cell spread, whereas tumor antigen transfer into and presentation in tumor-draining lymph nodes induce activation of tumor-specific T-lymphocyte responses that can result in cytolytic targeting of the tumor. Here, we discuss the recently emerged controversial role of the lymphatic vessels in tumor dissemination and cancer immunotherapy.
Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: an open-label cohort study
Authors: Emanuel Della-Torre, Corrado Campochiaro, Giulio Cavalli, Giacomo De Luca, Angela Napolitano, Salvatore La Marca, Nicola Boffini, Valentina Da Prat, Gaetano Di Terlizzi, Marco Lanzillotta, Patrizia Rovere Querini, Annalisa Ruggeri, Giovanni Landoni, Moreno Tresoldi, Fabio Ciceri, ALberto Zangrillo, Francesco De Cobelli, Lorenzo Dagna
Journal: Annals of the Rheumatic Diseases (2020)

Objectives To assess the safety and efficacy of interleukin (IL)−6 blockade with sarilumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation. Methods We conducted an open-label study of sarilumab in severe COVID-19 pneumonia (PaO 2 /FiO 2 &lt;300 mm Hg) with hyperinflammation (elevated inflammatory markers and serum IL-6 levels). Sarilumab 400 mg was administered intravenously in addition to standard of care and results were compared with contemporary matched patients treated with standard of care alone. Clinical improvement, mortality, safety and predictors of response were assessed at 28 days. Results Twenty-eight patients were treated with sarilumab and 28 contemporary patients receiving standard of care alone were used as controls. At day 28 of follow-up, 61% of patients treated with sarilumab experienced clinical improvement and 7% died. These findings were not significantly different from the comparison group (clinical improvement 64%, mortality 18%; p=NS). Baseline PaO 2 /FiO 2 ratio &gt;100 mm Hg and lung consolidation &lt;17% at CT scan predicted clinical improvement in patients treated with sarilumab. Median time to clinical improvement in patients with lung consolidation &lt;17% was shorter after sarilumab (10 days) than after standard treatment (24 days; p=0.01). The rate of infection and pulmonary thrombosis was similar between the two groups. Conclusions At day 28, overall clinical improvement and mortality in patients with severe COVID-19 were not significantly different between sarilumab and standard of care. Sarilumab was associated with faster recovery in a subset of patients showing minor lung consolidation at baseline.
Association of Checklist Use in Endotracheal Intubation With Clinically Important Outcomes
Authors: Joseph S. Turner, Antonino W. Bucca, Steven L. Propst, Timothy J. Ellender, Elisa J. Sarmiento, Laura M. Menard, Benton R. Hunter
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Endotracheal intubation of critically ill patients is a high-risk procedure. Checklists have been advocated to improve outcomes. <h3>Objective</h3> To assess whether the available evidence supports an association of use of airway checklists with improved clinical outcomes in patients undergoing endotracheal intubation. <h3>Data Sources</h3> For this systematic review and meta-analysis, PubMed (OVID), Embase, Cochrane, CINAHL, and SCOPUS were searched without limitations using the Medical Subject Heading terms and keywords<i>airway</i>;<i>management</i>;<i>airway management</i>;<i>intubation, intratracheal</i>;<i>checklist</i>; and<i>quality improvement</i>to identify studies published between January 1, 1960, and June 1, 2019. A supplementary search of the gray literature was performed, including conference abstracts and clinical trial registries. <h3>Study Selection</h3> Full-text reviews were performed to determine final eligibility for inclusion. Included studies were randomized clinical trials or observational human studies that compared checklist use with any comparator for endotracheal intubation and assessed 1 of the predefined outcomes. <h3>Data Extraction and Synthesis</h3> Data extraction and quality assessment were performed using the Newcastle-Ottawa Scale for observational studies and Cochrane risk of bias tool for randomized clinical trials. Study results were meta-analyzed using a random-effects model. Reporting of this study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. <h3>Main Outcomes and Measures</h3> The primary outcome was mortality. Secondary outcomes included first-pass success and known complications of endotracheal intubation, including esophageal intubation, hypoxia, hypotension, and cardiac arrest. <h3>Results</h3> The search identified 1649 unique citations of which 11 (3261 patients) met the inclusion criteria. One randomized clinical trial and 3 observational studies had a low risk of bias. Checklist use was not associated with decreased mortality (5 studies [2095 patients]; relative risk, 0.97; 95% CI, 0.80-1.18;<i>I</i><sup>2</sup> = 0%). Checklist use was associated with a decrease in hypoxic events (8 studies [3010 patients]; relative risk, 0.75; 95% CI, 0.59-0.95;<i>I</i><sup>2</sup> = 33%) but no other secondary outcomes. Studies with a low risk of bias did not demonstrate decreased hypoxia associated with checklist use. <h3>Conclusions and Relevance</h3> The findings suggest that use of airway checklists is not associated with improved clinical outcomes during and after endotracheal intubation, which may affect practitioners' decision to use checklists in this setting.
Exposure to Air Pollution and Particle Radioactivity With the Risk of Ventricular Arrhythmias
Authors: Adjani A. Peralta, Mark S. Link, Joel Schwartz, Heike Luttmann-Gibson, Douglas W. Dockery, Annelise Blomberg, Yaguang Wei, Murray A. Mittleman, Diane R. Gold, Francine Laden, Brent A. Coull, Petros Koutrakis
Journal: Circulation (2020)

Individuals are exposed to air pollution and ionizing radiation from natural sources through inhalation of particles. This study investigates the association between cardiac arrhythmias and short-term exposures to fine particulate matter (particulate matter ≤2.5 µm aerodynamic diameter; PM2.5) and particle radioactivity.Ventricular arrhythmic events were identified among 176 patients with dual-chamber implanted cardioverter-defibrillators in Boston, Massachusetts between September 2006 and June 2010. Patients were assigned exposures based on residential addresses. Daily PM2.5 levels were estimated at 1-km×1-km grid cells from a previously validated prediction model. Particle gross β activity was used as a surrogate for particle radioactivity and was measured from several monitoring sites by the US Environmental Protection Agency's monitoring network. The association of the onset of ventricular arrhythmias (VA) with 0- to 21-day moving averages of PM2.5 and particle radioactivity (2 single-pollutant models and a 2-pollutant model) before the event was examined using time-stratified case-crossover analyses, adjusted for dew point and air temperatures.A total of 1,050 VA were recorded among 91 patients, including 123 sustained VA among 25 of these patients. In the single-pollutant model of PM2.5, each interquartile range increase in daily PM2.5 levels for a 21-day moving average was associated with 39% higher odds of a VA event (95% CI, 12%-72%). In the single-pollutant model of particle radioactivity, each interquartile range increase in particle radioactivity for a 2-day moving average was associated with 13% higher odds of a VA event (95% CI, 1%-26%). In the 2-pollutant model, for the same averaging window of 21 days, each interquartile range increase in daily PM2.5 was associated with an 48% higher odds of a VA event (95% CI, 15%-90%), and each interquartile range increase of particle radioactivity with a 10% lower odds of a VA event (95% CI, -29% to 14%). We found that with higher levels of particle radioactivity, the effect of PM2.5 on VAs is reduced.In this high-risk population, intermediate (21-day) PM2.5 exposure was associated with higher odds of a VA event onset among patients with known cardiac disease and indication for implanted cardioverter-defibrillator implantation independently of particle radioactivity.
Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children
Authors: Amy-Sarah Ginsburg, Tisungane Mvalo, Evangelyn Nkwopara, Eric D. McCollum, Melda Phiri, Robert Schmicker, Jun Hwang, Chifundo B. Ndamala, Ajib Phiri, Norman Lufesi, Susanne May
Journal: New England Journal of Medicine (2020)

Evidence regarding the appropriate duration of treatment with antibiotic agents in children with pneumonia in low-resource settings in Africa is lacking.We conducted a double-blind, randomized, controlled, noninferiority trial in Lilongwe, Malawi, to determine whether treatment with amoxicillin for 3 days is less effective than treatment for 5 days in children with chest-indrawing pneumonia (cough lasting <14 days or difficulty breathing, along with visible indrawing of the chest wall with or without fast breathing for age). Children not infected with human immunodeficiency virus (HIV) who were 2 to 59 months of age and had chest-indrawing pneumonia were randomly assigned to receive amoxicillin twice daily for either 3 days or 5 days. Children were followed for 14 days. The primary outcome was treatment failure by day 6; noninferiority of the 3-day regimen to the 5-day regimen would be shown if the percentage of children with treatment failure in the 3-day group was no more than 1.5 times that in the 5-day group. Prespecified secondary analyses included assessment of treatment failure or relapse by day 14.From March 29, 2016, to April 1, 2019, a total of 3000 children underwent randomization: 1497 children were assigned to the 3-day group, and 1503 to the 5-day group. Among children with day 6 data available, treatment failure had occurred in 5.9% in the 3-day group (85 of 1442 children) and in 5.2% (75 of 1456) in the 5-day group (adjusted difference, 0.7 percentage points; 95% confidence interval [CI], -0.9 to 2.4) - a result that satisfied the criterion for noninferiority of the 3-day regimen to the 5-day regimen. Among children with day 14 data available, 176 of 1411 children (12.5%) in the 3-day group and 154 of 1429 (10.8%) in the 5-day group had had treatment failure by day 6 or relapse by day 14 (between-group difference, 1.7 percentage points; 95% CI, -0.7 to 4.1). The percentage of children with serious adverse events was similar in the two groups (9.8% in the 3-day group and 8.8% in the 5-day group).In HIV-uninfected Malawian children, treatment with amoxicillin for chest-indrawing pneumonia for 3 days was noninferior to treatment for 5 days. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02678195.).
Significant association of cutaneous adverse events with hydroxyurea: results from a prospective non-interventional study in BCR-ABL1-negative myeloproliferative neoplasms (MPN) - on behalf of the German Study Group-MPN
Authors: Frank Stegelmann, Kai Wille, Hannah Busen, Christiane Fuchs, Stefanie Schauer, Parvis Sadjadian, Tatjana Becker, Vera Kolatzki, Hartmut Döhner, Rudolf Stadler, Konstanze Döhner, Martin Griesshammer
Journal: Leukemia (2020)
Caspofungin for invasive aspergillosis: A single-centre prospective study
Authors: A. Bonini, A. Tieghi, B. Gamberi, A. Imovilli, C. Carbonelli, L. Spaggiari, L. Gugliotta
Journal: Journal of Clinical Oncology (2009)

e20618 Background: Infections are the main complication for neutropenic patients (pts).Fungal infections represent a frequent cause of death. Caspofungin (Caspo) is the first drug able to inhibit the growth of the fungal cell wall. Methods: Since 2004 we began a prospective study with the administration of Caspo as first line therapy in 63 consecutive adult neutropenic pts. With persistent fever despite antibiotics,a chest CT-scan and galactomannan test were performed. In case of probable or proven infection Caspo was administered at the dose of 70 mg on the first day followed by 50 mg daily. They were 35 males and 28 females; the mean age was 56 yrs. The diagnoses were: leukemia 44, myeloma 3, lymphoma 16; the disease's phases were: new onset 24, remission 16, relapse 23. 12 pts received an allogeneic and 6 an autologous transplant; the others received conventional chemotherapy. Results: Fungal infections were proven in 12 and probable in 51 cases.The first site of infection was the lung in 62 pts. CT scan was positive(halo sign or air-crescent sign)in all the pts with a lung localization. BAL was performed in 37 pts.The mean time of treatment was 18 days. Caspo was well tolerated and not discontinued for adverse events. Among pts submitted to an allogeneic HSCT the concomitant therapy with Cyclosporin A was not influenced by Caspo. No adverse events during the infusion were seen, and it was not necessary to administer any premedication. The global (partial and complete) response was 50/63 (79%); 13 pts died for fungal infection. The responses were generally similar for probable and proven infections. No breakthrough infections were seen. All surviving patients, upon discharge from the hospital, received oral treatment with voriconazole. For all the cured pts, there was a concomitant recovery of neutrophils and this seems crucial for the resolution of the infection. Among the 50 responsive patients, 25 died later: 23 for hematologic disease and 2 for sepsis during recurrence of the malignant disease. In 2 pts there was the recurrence of the fungal infection. Conclusions: The resolution rate of the infections is very high; Caspo seems safe, it does not preclude any other treatment, it is well tolerated and the cost is lower than other antifungal treatments. No significant financial relationships to disclose.
Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics
Authors: Eskild Petersen, Marion Koopmans, Unyeong Go, Davidson H Hamer, Nicola Petrosillo, Francesco Castelli, Merete Storgaard, Sulien Al Khalili, Lone Simonsen
Journal: The Lancet Infectious Diseases (2020)

The objective of this Personal View is to compare transmissibility, hospitalisation, and mortality rates for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with those of other epidemic coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and pandemic influenza viruses. The basic reproductive rate (R0) for SARS-CoV-2 is estimated to be 2·5 (range 1·8-3·6) compared with 2·0-3·0 for SARS-CoV and the 1918 influenza pandemic, 0·9 for MERS-CoV, and 1·5 for the 2009 influenza pandemic. SARS-CoV-2 causes mild or asymptomatic disease in most cases; however, severe to critical illness occurs in a small proportion of infected individuals, with the highest rate seen in people older than 70 years. The measured case fatality rate varies between countries, probably because of differences in testing strategies. Population-based mortality estimates vary widely across Europe, ranging from zero to high. Numbers from the first affected region in Italy, Lombardy, show an all age mortality rate of 154 per 100 000 population. Differences are most likely due to varying demographic structures, among other factors. However, this new virus has a focal dissemination; therefore, some areas have a higher disease burden and are affected more than others for reasons that are still not understood. Nevertheless, early introduction of strict physical distancing and hygiene measures have proven effective in sharply reducing R0 and associated mortality and could in part explain the geographical differences.
Coevolution in Hybrid Genomes: Nuclear-Encoded Rubisco Small Subunits and Their Plastid-Targeting Translocons Accompanying Sequential Allopolyploidy Events in<i>Triticum</i>
Authors: Changping Li, Xiaofei Wang, Yaxian Xiao, Xuhan Sun, Jinbin Wang, Xuan Yang, Yuchen Sun, Yan Sha, Ruili Lv, Yanan Yu, Baoxu Ding, Zhibin Zhang, Ning Li, Tianya Wang, Jonathan F Wendel, Bao Liu, Lei Gong
Journal: Molecular Biology and Evolution (2020)

The Triticum/Aegilops complex includes hybrid species resulting from homoploid hybrid speciation and allopolyploid speciation. Sequential allotetra- and allohexaploidy events presumably result in two challenges for the hybrids, which involve 1) cytonuclear stoichiometric disruptions caused by combining two diverged nuclear genomes with the maternal inheritance of the cytoplasmic organellar donor; and 2) incompatibility of chimeric protein complexes with diverged subunits from nuclear and cytoplasmic genomes. Here, we describe coevolution of nuclear rbcS genes encoding the small subunits of Rubisco (ribulose 1,5-bisphosphate carboxylase/oxygenase) and nuclear genes encoding plastid translocons, which mediate recognition and translocation of nuclear-encoded proteins into plastids, in allopolyploid wheat species. We demonstrate that intergenomic paternal-to-maternal gene conversion specifically occurred in the genic region of the homoeologous rbcS3 gene from the D-genome progenitor of wheat (abbreviated as rbcS3D) such that it encodes a maternal-like or B-subgenome-like SSU3D transit peptide in allohexaploid wheat but not in allotetraploid wheat. Divergent and limited interaction between SSU3D and the D-subgenomic TOC90D translocon subunit is implicated to underpin SSU3D targeting into the chloroplast of hexaploid wheat. This implicates early selection favoring individuals harboring optimal maternal-like organellar SSU3D targeting in hexaploid wheat. These data represent a novel dimension of cytonuclear evolution mediated by organellar targeting and transportation of nuclear proteins.
Methotrexate-loaded tumour-cell-derived microvesicles can relieve biliary obstruction in patients with extrahepatic cholangiocarcinoma
Authors: Yunfeng Gao, Hui Zhang, Nannan Zhou, Pingwei Xu, Jianxiong Wang, Yuan Gao, Xun Jin, Xiaoyu Liang, Jiadi Lv, Yamin Zhang, Ke Tang, Jingwei Ma, Huafeng Zhang, Jing Xie, Fang Yao, Weimin Tong, Yuying Liu, Ximo Wang, Bo Huang
Journal: Nature Biomedical Engineering (2020)
The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study
Authors: Jonathan Hewitt, Ben Carter, Arturo Vilches-Moraga, Terence J Quinn, Philip Braude, Alessia Verduri, Lyndsay Pearce, Michael Stechman, Roxanna Short, Angeline Price, Jemima T Collins, Eilidh Bruce, Alice Einarsson, Frances Rickard, Emma Mitchell, Mark Holloway, James Hesford, Fenella Barlow-Pay, Enrico Clini, Phyo K Myint, Susan J Moug, Kathryn McCarthy, Charlotte Davey, Sheila Jones, Kiah Lunstone, Alice Cavenagh, Charlotte Silver, Thomas Telford, Rebecca Simmons, Tarik El Jichi Mutasem, Sandeep Singh, Dolcie Paxton, Will Harris, Norman Galbraith, Emma Bhatti, Jenny Edwards, Siobhan Duffy, Carly Bisset, Ross Alexander, Madeline Garcia, Shefali Sangani, Thomas Kneen, Thomas Lee, Aine McGovern, Giovanni Guaraldi
Journal: The Lancet Public Health (2020)