tbuckley/cabot-search huggingface dataset:
Is Acetylsalicylic Acid a Safe and Potentially Useful Choice for Adult Patients with COVID-19 ?
Authors: Vanessa Bianconi, Francesco Violi, Francesca Fallarino, Pasquale Pignatelli, Amirhossein Sahebkar, Matteo Pirro
Journal: Drugs (2020)

Severe Acute Respiratory Syndrome-Coronavirus-2 is responsible for the current pandemic that has led to more than 10 million confirmed cases of Coronavirus Disease-19 (COVID-19) and over 500,000 deaths worldwide (4 July 2020). Virus-mediated injury to multiple organs, mainly the respiratory tract, activation of immune response with the release of pro-inflammatory cytokines, and overactivation of the coagulation cascade and platelet aggregation leading to micro- and macrovascular thrombosis are the main pathological features of COVID-19. Empirical multidrug therapeutic approaches to treat COVID-19 are currently used with extremely uncertain outcomes, and many others are being tested in clinical trials. Acetylsalicylic acid (ASA) has both anti-inflammatory and antithrombotic effects. In addition, a significant ASA-mediated antiviral activity against DNA and RNA viruses, including different human coronaviruses, has been documented. The use of ASA in patients with different types of infections has been associated with reduced thrombo-inflammation and lower rates of clinical complications and in-hospital mortality. However, safety issues related both to the risk of bleeding and to that of developing rare but serious liver and brain damage mostly among children (i.e., Reye's syndrome) should be considered. Hence, whether ASA might be a safe and reasonable therapeutic candidate to be tested in clinical trials involving adults with COVID-19 deserves further attention. In this review we provide a critical appraisal of current evidence on the anti-inflammatory, antithrombotic, and antiviral effects of ASA, from both a pre-clinical and a clinical perspective. In addition, the potential benefits and risks of use of ASA have been put in the context of the adult-restricted COVID-19 population.
Classification criteria: time for a rethink?
Authors: Duncan Porter, Neil Basu, Stefan Siebert
Journal: Annals of the Rheumatic Diseases (2020)

The last decade has seen the development or renewal of classification criteria in sundry rheumatic diseases, including systemic lupus erythematosus (SLE),1 rheumatoid arthritis2 and axial spondyloarthritis (axSpA).3 These criteria seek the laudable aim of standardising the populations included in clinical trials and observational cohorts for research purposes. But to what extent have the benefits of classification criteria been realised? Have there been unintended consequences as their profile has grown? And could we better use criteria to achieve the desired end of facilitating the implementation and interpretation of research findings to enable their translation into clinical practice?

We are all familiar with the refrain of key opinion leaders when they present their update on the management of a disease—‘These are classification criteria, not diagnostic criteria …’ But how often have we heard the same speaker move smoothly on to state, ‘… but I find them helpful in clinical practice too’? Indeed, the abstract of the original paper describing the validation and final selection of the classification criteria for axSpA concluded with the statement that ‘The new Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (SpA) … may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain’.3

However, the dangers of applying classification criteria to clinical practice for the purpose of diagnosis are easily demonstrated. The criteria are invariably developed and validated in specialist centres where there is a high prior (pretest) probability of the disease, and they are evaluated based on a clinical diagnosis of the disease in question made by experts in that condition, after alternative causes or explanations for the patient’s symptoms have been excluded. When the criteria are applied to a different population—for instance, in primary care—where there is a low prior (pretest) probability of …
AB0554 CONCORDANCE IN THE CLASSIFICATION CRITERIA IN A PATIENT COHORT WITH IDIOPATHIC INFLAMMATORY MYOPATHIES (IIM).
Authors: F. Bozan, S. Saavedra, K. Vergara, A. Goecke, H. Gatica
Journal: Annals of the Rheumatic Diseases (2020)

Background: Differents classifications criteria for IIM exist. New classification criteria are superior to previous in capturing different subgroups of IIM. Objectives: To compare the concordance and disparity of Bohan and Peter and EULAR/ACR 2017 classification criteria at the level of diagnostic certainty, in a group of chilean patients with IIM. Methods: 40 adults patients with IIM (27 Dermatomyositis (DM) and 13 Polimyositis (PM)), according Bohan and Peter criteria were analized. The patients were reclassified with EULAR/ACR criteria. The level of diagnostic certainty (definitive, probable and possible) was registered for both Classification Criteria. The concordance and disparity between criteria was evaluated. Concordance and disparity analysis were made considering the strict agreement between level of certainty of both criteria, using Cohen´s Kappa coefficient. The analysis was done for the complete cohort and for separated groups. Patients with discordance belonging to the same subgroup were evaluated using contingency tables. The direction of the change (gain or lost of certainty) and the relation with diagnostic subgroup was also analized. Descriptive statistics is expressed as diagnostic categories, number of patients and rates. Results: For the complete cohort and for DM and PM groups the concordance was low. For 27 patients with DM, the observed concordance rate was 63% (16 definitives, 1 probable). The observed disparity rate was 37%. The direction of the change was gain of one level of certainty in 14.5% and two levels in 22.2% of patients applying EULAR/ACR criteria compared to Bohan y Peter criteria. For 13 pacients with PM, the observed concordance rate was 46% (3 definitives and 3 probables). The observed disparity rate was 54%. The direction of the change was loss of certainty. The loss of certainty was one level in 85,7% (one patient change from probable to posible). Only one patiente had gain of certainty of one level (14.3%). Conclusion: The strict concordance between both classification criteria was low. The observed concordances were better in patients with DM that PM. The disparities involved gain of level of diagnostic certainty in DM patients, while in PM patients there was mostly lost of level of certainty. References: [1]Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). NEJM 1975;292:344-7. [2]Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). NEJM 1975;292:403-7. [3]2017 European League Against Rheumatism/American Colllege of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their major Subgroups. Arthritis Rheum 2017;0:1-12. Disclosure of Interests: : None declared
Endoscopic ultrasound-guided placement of biliary lumen-apposing metal stent through a duodenal stent
Authors: Jawad Rasool, Carthage Moran, Danny Cheriyan
Journal: Endoscopy (2020)

Endoscopic management of a malignant biliary obstruction becomes a significant challenge in the setting of an existing duodenal stent [1]. Progressive malignancy often causes stenosis of the duodenal stent, which renders it impassable by a duodenoscope. Options for biliary decompression include percutaneous drainage or endoscopic ultrasound (EUS)-guided choledochoduodenostomy or hepaticogastrostomy. We describe the case of an EUS-guided choledochoduodenostomy using a lumen-apposing metal stent (LAMS) through the struts of an existing duodenal stent([Video 1]).
AB0858 TREATMENT ALGORITHM FOR ANKLE OSTEOCHONDRAL LESIONS AND DEFECTS
Authors: O. Burianov, L. Khimion, T. Omelchenko, E. Levitskyi, V. Lyanskorynsky
Journal: Annals of the Rheumatic Diseases (2020)

Background: traumatic ankle joint osteochondral lesions and defects (OHLD) is frequent cause of OA, chronic pain and loss of joint function; results of traditional treatment strategy are often unsatisfying Objectives: to develop treatment algorithm for OHLD based on evaluation of previously determined main prognostic factors. Methods: the analysis of long-term (36 ± 4.5 months) treatment results of 239 patients after traumatic ankle joint OHLD revealed the following factors with the greatest predictive value (defined by PC – prognostic coefficient) for good result of treatment (defined as AOFAS function score 75-100 points): age &lt; 40 years (PC = 8.5); size of OHLD ≤ 1.0 cm 2 ; volume ≤ 1.5 cm 3 (PC = 8.0); osteoarthritis stage ≤ II (PC = 7.2). Based on these factors, a step-by-step, discrete and alternative algorithm for the choice of treatment tactics was created. The algorithm includes use of arthroscopic or open debridement, abrasive chondroplasty, bone marrow regeneration stimulation (microfracturing or tunneling), mosaic osteochondroplasty, arthroplasty or arthrodesis, the use of cellular regenerative technologies (bone marrow cells, platelet riched plasma), and others. Patients of older age with advanced OA need complex, step up approach, surgical treatment combined with regenerative cell technologies. The effectiveness of the differentiated approach to treatment was studied in 72 patients with OHLD (main group) in comparing to 72 patients in whom traditional treatment approaches were used, based on the stage of injury according to the Berndt &amp; Hardy classification (comparison group). Results: compared to the traditional approach, the developed algorithm and treatment system allowed to half terms of hospitalization, to reduce the intensity of pain syndrome (by NRS) and increase the functional activity (by AOFAS) by 25%. In 3 years after trauma good/excellent results of treatment demonstrated 86% patients of main group and 32,2% of patients from comparing group (p&lt;0,05). Conclusion: implementation of the developed treatment algorithm increases the number of good and excellent long-term results by 2.6 times and reduces the number of complications and unsatisfactory results by 4.9 times. Disclosure of Interests: None declared
Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia
Authors: Andrés Pizzorno, Blandine Padey, Thomas Julien, Sophie Trouillet-Assant, Aurélien Traversier, Elisabeth Errazuriz-Cerda, Julien Fouret, Julia Dubois, Alexandre Gaymard, François-Xavier Lescure, Victoria Dulière, Pauline Brun, Samuel Constant, Julien Poissy, Bruno Lina, Yazdan Yazdanpanah, Olivier Terrier, Manuel Rosa-Calatrava
Journal: Cell Reports Medicine (2020)

In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need.
Net benefit and cost-effectiveness of universal iron-containing multiple micronutrient powders for young children in 78 countries: a microsimulation study
Authors: Sant-Rayn Pasricha, Adrian Gheorghe, Fayrouz Sakr-Ashour, Amrita Arcot, Lynnette Neufeld, Laura E Murray-Kolb, Parminder S Suchdev, Michael Bode
Journal: The Lancet Global Health (2020)

Universal home fortification of complementary foods with iron-containing multiple micronutrient powders (MNPs) is a key intervention to prevent anaemia in young children in low-income and middle-income countries. However, evidence that MNPs might promote infection raises uncertainty about whether MNPs give net health benefits and are cost-effective. We aimed to determined country-specific net benefit or harm and cost-effectiveness of universal provision of MNPs to children aged 6 months.We developed a microsimulation model to estimate net country-specific disability-adjusted life-years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) due to anaemia, malaria, and diarrhoea averted (or increased) by provision of a 6-month course of MNPs to children aged 6 months, compared with no intervention, who would be followed up for an additional 6 months (ie, to age 18 months). Anaemia prevalence was derived from Demographic and Health Surveys or similar national surveys, and malaria and diarrhoea incidence were sourced from the Global Burden of Disease Study. Programme and health-care costs were modelled to determine cost per DALY averted (US$). Additionally, we explored the effects of reduced MNP coverage in a sensitivity analysis.78 countries (46 countries in Africa, 20 in Asia or the Middle East, and 12 in Latin America) were included in the analysis, and we simulated 5 million children per country. 6 months of universal distribution of daily MNPs, assuming 100% coverage, produced a net benefit (DALYs averted) in 54 countries (24 in Africa, 19 in Asia and the Middle East, 11 in Latin America) and net harm in 24 countries (22 in Africa, one in Asia, and one in Latin America). MNP intervention provided a benefit on YLDs associated with anaemia, but these gains were attenuated and sometimes reversed by increases in YLLs associated with malaria and diarrhoea, reducing the benefits seen for DALYs. In the 54 countries where MNP provision was beneficial, the median benefit was 28·1 DALYs averted per 10 000 children receiving MNPs (IQR 20·6-40·4), and median cost per DALY averted was $3576 (IQR 2474-4918). DALY effects positively correlated with moderate and severe anaemia prevalence in Asia, the Middle East, and Latin America, but correlated inversely in Africa. Suboptimal coverage markedly reduced DALYs averted and cost-effectiveness.Net health benefits of MNPs vary between countries, are highest where prevalence of moderate and severe anaemia is greatest but infection prevalence is smallest, and are ameliorated when coverage of the intervention is poor. Our data provide country-specific guidance to national policy makers.International Union of Nutrition Sciences.
Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome
Authors: Matthew C. Sims, Louisa Mayer, Janine H. Collins, Tadbir K. Bariana, Karyn Megy, Cecile Lavenu-Bombled, Denis Seyres, Laxmikanth Kollipara, Frances S. Burden, Daniel Greene, Dave Lee, Antonio Rodriguez-Romera, Marie-Christine Alessi, William J. Astle, Wadie F. Bahou, Loredana Bury, Elizabeth Chalmers, Rachael Da Silva, Erica De Candia, Sri V. V. Deevi, Samantha Farrow, Keith Gomez, Luigi Grassi, Andreas Greinacher, Paolo Gresele, Dan Hart, Marie-Françoise Hurtaud, Anne M. Kelly, Ron Kerr, Sandra Le Quellec, Thierry Leblanc, Eva B. Leinøe, Rutendo Mapeta, Harriet McKinney, Alan D. Michelson, Sara Morais, Diane Nugent, Sofia Papadia, Soo J. Park, John Pasi, Gian Marco Podda, Man-Chiu Poon, Rachel Reed, Mallika Sekhar, Hanna Shalev, Suthesh Sivapalaratnam, Orna Steinberg-Shemer, Jonathan C. Stephens, Robert C. Tait, Ernest Turro, John K. M. Wu, Barbara Zieger, Taco W. Kuijpers, Anthony D. Whetton, Albert Sickmann, Kathleen Freson, Kate Downes, Wendy N. Erber, Mattia Frontini, Paquita Nurden, Willem H. Ouwehand, Remi Favier, Jose A. Guerrero
Journal: Blood (2020)
Association of Initial Illness Severity and Outcomes After Cardiac Arrest With Targeted Temperature Management at 36 °C or 33 °C
Authors: Clifton W. Callaway, Patrick J. Coppler, John Faro, Jacob S. Puyana, Pawan Solanki, Cameron Dezfulian, Ankur A. Doshi, Jonathan Elmer, Adam Frisch, Francis X. Guyette, Masashi Okubo, Jon C. Rittenberger, Alexandra Weissman
Journal: JAMA Network Open (2020)

<h3>Importance</h3> It is uncertain what the optimal target temperature is for targeted temperature management (TTM) in patients who are comatose following cardiac arrest. <h3>Objective</h3> To examine whether illness severity is associated with changes in the association between target temperature and patient outcome. <h3>Design, Setting, and Participants</h3> This cohort study compared outcomes for 1319 patients who were comatose after cardiac arrest at a single center in Pittsburgh, Pennsylvania, from January 2010 to December 2018. Initial illness severity was based on coma and organ failure scores, presence of severe cerebral edema, and presence of highly malignant electroencephalogram (EEG) after resuscitation. <h3>Exposure</h3> TTM at 36 °C or 33 °C. <h3>Main Outcomes and Measures</h3> Primary outcome was survival to hospital discharge, and secondary outcomes were modified Rankin Scale and cerebral performance category. <h3>Results</h3> Among 1319 patients, 728 (55.2%) had TTM at 33 °C (451 [62.0%] men; median [interquartile range] age, 61 [50-72] years) and 591 (44.8%) had TTM at 36 °C (353 [59.7%] men; median [interquartile range] age, 59 [48-69] years). Overall, 184 of 187 patients (98.4%) with severe cerebral edema died and 234 of 243 patients (96.3%) with highly malignant EEG died regardless of TTM strategy. Comparing TTM at 33 °C with TTM at 36 °C in 911 patients (69.1%) with neither severe cerebral edema nor highly malignant EEG, survival was lower in patients with mild to moderate coma and no shock (risk difference, –13.8%; 95% CI, –24.4% to –3.2%) but higher in patients with mild to moderate coma and cardiopulmonary failure (risk difference, 21.8%; 95% CI, 5.4% to 38.2%) or with severe coma (risk difference, 9.7%; 95% CI, 4.0% to 15.3%). Interactions were similar for functional outcomes. Most deaths (633 of 968 [65.4%]) resulted after withdrawal of life-sustaining therapies. <h3>Conclusions and Relevance</h3> In this study, TTM at 33 °C was associated with better survival than TTM at 36 °C among patients with the most severe post–cardiac arrest illness but without severe cerebral edema or malignant EEG. However, TTM at 36 °C was associated with better survival among patients with mild- to moderate-severity illness.
Dapagliflozin promotes beta cell regeneration by inducing pancreatic endocrine cell phenotype conversion in type 2 diabetic mice
Authors: Rui Wei, Xiaona Cui, Jin Feng, Liangbiao Gu, Shan Lang, Tianjiao Wei, Jin Yang, Junling Liu, Yunyi Le, Haining Wang, Kun Yang, Tianpei Hong
Journal: Metabolism (2020)

BackgroundClinical trials and animal studies have shown that sodium-glucose co-transporter type 2 (SGLT2) inhibitors improve pancreatic beta cell function. Our study aimed to investigate the effect of dapagliflozin on islet morphology and cell phenotype, and explore the origin and possible reason of the regenerated beta cells.MethodsTwo diabetic mouse models, db/db mice and pancreatic alpha cell lineage-tracing (glucagon-β-gal) mice whose diabetes was induced by high fat diet combined with streptozotocin, were used. Mice were treated by daily intragastric administration of dapagliflozin (1 mg/kg) or vehicle for 6 weeks. The plasma insulin, glucagon and glucagon-like peptide-1 (GLP-1) were determined by using ELISA. The evaluation of islet morphology and cell phenotype was performed with immunofluorescence. Primary rodent islets and αTC1.9, a mouse alpha cell line, were incubated with dapagliflozin (0.25–25 μmol/L) or vehicle in the presence or absence of GLP-1 receptor antagonist for 24 h in regular or high glucose medium. The expression of specific markers and hormone levels were determined.ResultsTreatment with dapagliflozin significantly decreased blood glucose in the two diabetic models and upregulated plasma insulin and GLP-1 levels in db/db mice. The dapagliflozin treatment increased islet and beta cell numbers in the two diabetic mice. The beta cell proliferation as indicated by C-peptide and BrdU double-positive cells was boosted by dapagliflozin. The alpha to beta cell conversion, as evaluated by glucagon and insulin double-positive cells and confirmed by using alpha cell lineage-tracing, was facilitated by dapagliflozin. After the dapagliflozin treatment, some insulin-positive cells were located in the duct compartment or even co-localized with duct cell markers, suggestive of duct-derived beta cell neogenesis. In cultured primary rodent islets and αTC1.9 cells, dapagliflozin upregulated the expression of pancreatic endocrine progenitor and beta cell specific markers (including Pdx1) under high glucose condition. Moreover, dapagliflozin upregulated the expression of Pcsk1 (which encodes prohormone convertase 1/3, an important enzyme for processing proglucagon to GLP-1), and increased GLP-1 content and secretion in αTC1.9 cells. Importantly, the dapagliflozin-induced upregulation of Pdx1 expression was attenuated by GLP-1 receptor antagonist.ConclusionsExcept for glucose-lowering effect, dapagliflozin has extra protective effects on beta cells in type 2 diabetes. Dapagliflozin enhances beta cell self-replication, induces alpha to beta cell conversion, and promotes duct-derived beta cell neogenesis. The promoting effects of dapagliflozin on beta cell regeneration may be partially mediated via GLP-1 secreted from alpha cells.
Abstract 12169: Comparison of Management Strategies for the Neonate With Symptomatic Tetralogy of Fallot: A Study From the Congenital Catheterization Research Collaborative
Authors: Bryan H Goldstein, Christopher J Petit, Athar M Qureshi, Courtney E McCracken, Michael S Kelleman, George T Nicholson, Mark A Law, Jeffery J Meadows, Jeffrey D Zampi, Shabana Shahanavaz, Christopher E Mascio, Paul J Chai, Jennifer C Romano, Ivor B Asztalos, Lindsay F Eilers, Alicia M Kamsheh, Steven J Healan, Justin Smith, R. Allen Ligon, Sarina Juma, James E Raulston, Sarosh P Batlivala, Hala Q Khan, Taylor C Merritt, Matthew Candor, Stephan Juergensen, Fatuma A Rinderknecht, Amy L Pajk, Joelle A Pettus, Holly Bauser Heaton, Andrew C Glatz
Journal: Circulation (2019)

Introduction: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention. Management strategies include initial palliation (IP) followed by later complete repair (...