tbuckley/cabot-search huggingface dataset:
Abstract 16790: Generation of Induced Pluripotent Stem Cell-derived Cardiomyocytes From Peripheral Blood Mononuclear Cells of Patients With Atrial Fibrillation
Authors: Sanghamitra Mohanty, Shuying Zhao, Austin Conney, Andrea Natale, Hongran Wang
Journal: Circulation (2017)

Introduction: Human induced pluripotent stem cells (iPSCs) have attracted considerable attention for disease modeling studies. However, there are rare instances when peripheral blood mononuclear ce...
Two Distinct but Functionally Related Autoreactive T Cell Populations in Paroxysmal Nocturnal Hemoglobinuria and Idiopathic Aplastic Anemia: Glycosylphosphatidylinositol-Specific and IFNγ-Producing T Cells
Authors: Lucia Gargiulo, Michela Sica, Caterina Nannelli, Lucio Luzzatto, Rosario Notaro
Journal: Blood (2017)
Universal Drug Coverage and Socioeconomic Disparities in Health Care Costs Among Persons With Diabetes
Authors: Wanrudee Isaranuwatchai, Ghazal S. Fazli, Arlene S. Bierman, Lorraine L. Lipscombe, Nicholas Mitsakakis, Baiju R. Shah, C. Fangyun Wu, Ashley Johns, Gillian L. Booth
Journal: Diabetes Care (2020)

OBJECTIVE To examine whether neighborhood socioeconomic status (SES) is a predictor of non-drug-related health care costs among Canadian adults with diabetes and, if so, whether SES disparities in costs are reduced after age 65 years, when universal drug coverage commences as an insurable benefit. RESEARCH DESIGN AND METHODS Administrative health databases were used to examine publicly funded health care expenditures among 698,113 younger (20–64 years) and older (≥65 years) adults with diabetes in Ontario from April 2004 to March 2014. Generalized linear models were constructed to examine relative and absolute differences in health care costs (total and non-drug-related costs) across neighborhood SES quintiles, by age, with adjustment for differences in age, sex, diabetes duration, and comorbidity. RESULTS Unadjusted costs per person-year in the lowest SES quintile (Q1) versus the highest (Q5) were 39% higher among younger adults ($5,954 vs. $4,270 [Canadian dollars]) but only 9% higher among older adults ($10,917 vs. $9,993). Adjusted non-drug costs (primarily for hospitalizations and physician visits) were $1,569 per person-year higher among younger adults in Q1 vs. Q5 (modeled relative cost difference: 35.7% higher) and $139.3 million per year among all individuals in Q1. Scenarios in which these excess costs per person-year were decreased by ≥10% or matched the relative difference among seniors suggested a potential for savings in the range of $26.0–$128.2 million per year among all lower-SES adults under age 65 years (Q1–Q4). CONCLUSIONS SES is a predictor of diabetes-related health care costs in our setting, more so among adults under age 65 years, a group that lacks universal drug coverage under Ontario’s health care system. Non-drug-related health care costs were more than one-third higher in younger, lower-SES adults, translating to &amp;gt;$1 billion more in health care expenditures over 10 years.
Burkholderia pseudomallei multi-centre study to establish EUCAST MIC and zone diameter distributions and epidemiological cut-off values
Authors: O. Karatuna, D.A.B. Dance, E. Matuschek, J. Åhman, P. Turner, J. Hopkins, P. Amornchai, V. Wuthiekanun, T.-P. Cusack, R. Baird, J. Hennessy, R. Norton, M. Armstrong, S. Zange, L. Zoeller, T. Wahab, D. Jacob, R. Grunow, G. Kahlmeter
Journal: Clinical Microbiology and Infection (2020)

ObjectivesMelioidosis, caused by Burkholderia pseudomallei, requires intensive antimicrobial treatment. However, standardized antimicrobial susceptibility testing (AST) methodology based on modern principles for determining breakpoints and ascertaining performance of methods are lacking for B. pseudomallei. This study aimed to establish MIC and zone diameter distributions on which to set epidemiological cut-off (ECOFF) values for B. pseudomallei using standard EUCAST methodology for non-fastidious organisms.MethodsNon-consecutive, non-duplicate clinical B. pseudomallei isolates (9–70 per centre) were tested at eight study centres against eight antimicrobials by broth microdilution (BMD) and the EUCAST disc diffusion method. Isolates without and with suspected resistance mechanisms were deliberately selected. The EUCAST Development Laboratory ensured the quality of study materials, and provided guidance on performance of the tests and interpretation of results. Aggregated results were analysed according to EUCAST recommendations to determine ECOFFs.ResultsMIC and zone diameter distributions were generated using BMD and disc diffusion results obtained for 361 B. pseudomallei isolates. MIC and zone diameter ECOFFs (mg/L; mm) were determined for amoxicillin-clavulanic acid (8; 22), ceftazidime (8; 22), imipenem (2; 29), meropenem (2; 26), doxycycline (2; none), tetracycline (8; 23), chloramphenicol (8; 22) and trimethoprim-sulfamethoxazole (4; 28).ConclusionsWe have validated the use of standard BMD and disc diffusion methodology for AST of B. pseudomallei. The MIC and zone diameter distributions generated in this study allowed us to establish MIC and zone diameter ECOFFs for the antimicrobials studied. These ECOFFs served as background data for EUCAST to set clinical MIC and zone diameter breakpoints for B. pseudomallei.
Bacteroides thetaiotaomicron-Infecting Bacteriophage Isolates Inform Sequence-Based Host Range Predictions
Authors: Andrew J. Hryckowian, Bryan D. Merrill, Nathan T. Porter, William Van Treuren, Eric J. Nelson, Rebecca A. Garlena, Daniel A. Russell, Eric C. Martens, Justin L. Sonnenburg
Journal: Cell Host & Microbe (2020)
The Association between Discharge Delay from Intensive Care and Patient Outcomes
Authors: Gareth Mitchell Forster, Shailesh Bihari, Ravindranath Tiruvoipati, Michael Bailey, David Pilcher
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: ICU discharge delay occurs when a patient is considered ready to be discharged but remains in the ICU. The effect of discharge delay on patient outcomes is uncertain.Objectives: To investigate the association between discharge delay and patient outcomes including hospital mortality, readmission to ICU, and length of hospital stay after ICU discharge.Methods: Data were accessed from the Australian and New Zealand Intensive Care Society Adult Patient Database between 2011 and 2019. Descriptive analyses and hierarchical logistic and Cox proportional hazards regression were used to examine association between discharge delay and adjusted outcomes. Patients were stratified and analyzed by categories of mortality risk at ICU admission.Measurements and Main Results: The study included 1,014,540 patients from 190 ICUs: 756,131 (75%) were discharged within 6 hours of being deemed ready, with 137,042 (13%) discharged in the next 6 hours; 17,656 (2%) were delayed 48-72 hours; 31,389 (3.1%) died in hospital; and 45,899 (4.5%) patients were readmitted to ICU. Risk-adjusted mortality declined with increasing discharge delay and was lowest at 48-72 hours (adjusted odds ratio, 0.87; 95% confidence interval, 0.79-0.94). The effect was seen in patients with predicted risk of death on admission to ICU of greater than 5% (adjusted odds ratio, 0.77; 95% confidence interval, 0.70-0.84). There was a progressive reduction in adjusted odds of readmission with increasing discharge delay.Conclusions: Increasing discharge delay in ICUs is associated with reduced likelihood of mortality and ICU readmission in high-risk patients. Consideration should be given to delay the discharge of patients with high risk of death on ICU admission.
Predicting covid-19 resurgence: do it locally
Authors: Arnaud Chiolero
Journal: BMJ (2020)

This week, 13 June

The debate on how to use mathematical simulations to predict the impact of covid-19 on population health and healthcare needs is ongoing.1 While some researchers have predicted a huge number of deaths and overwhelmed healthcare systems,2 others have forecast a much smaller burden.3 Now, predictions aim to estimate the probability and the scale of a second wave.1 Many prediction …
Abstract 17836: High Throughput Functional Screening Identifies microRNAs Inducing Cardiac Regeneration
Authors: Mauro Giacca, Ana Eulalio, Miguel Mano, Matteo Dal Ferro, Giulia Felician, Valentina Martinelli, Lorena Zentilin, Gianfranco Sinagra, Serena Zacchigna
Journal: Circulation (2013)

Whereas enlargement of the heart during mammalian development relies on cardiomyocyte proliferation, at birth cardiomyocytes stop dividing and further growth occurs through hypertrophy. As a conseq...
Sustainable Tumor-Suppressive Effect of iPSC-Derived Rejuvenated T Cells Targeting Cervical Cancers
Authors: Tadahiro Honda, Miki Ando, Jun Ando, Midori Ishii, Yumi Sakiyama, Kazuo Ohara, Tokuko Toyota, Manami Ohtaka, Ayako Masuda, Yasuhisa Terao, Mahito Nakanishi, Hiromitsu Nakauchi, Norio Komatsu
Journal: Molecular Therapy (2020)

Immunotherapy utilizing induced pluripotent stem cell (iPSC) technology has great potential. Functionally rejuvenated cytotoxic T lymphocytes (CTLs) can survive long-term as young memory T cells in vivo, with continuous tumor eradication. Banking of iPSCs as an unlimited "off-the-shelf" source of therapeutic T cells may be feasible. To generate safer iPSCs, we reprogrammed human papilloma virus type 16 (HPV16) E6-specific CTLs by Sendai virus vector without cotransduction of SV40 large T antigen. The iPSCs efficiently differentiated into HPV16-specific rejuvenated CTLs that demonstrated robust cytotoxicity against cervical cancer. The tumor-suppressive effect of rejuvenated CTLs was stronger and more persistent than that of original peripheral blood CTLs. These rejuvenated HPV16-specific CTLs provide a sustained tumor-suppressive effect even for epithelial cancers and constitute promising immunotherapy for cervical cancer.
Comparison of the FreeStyle Libre Pro Flash Continuous Glucose Monitoring (CGM) System and Point-of-Care Capillary Glucose Testing in Hospitalized Patients With Type 2 Diabetes Treated With Basal-Bolus Insulin Regimen
Authors: Rodolfo J. Galindo, Alexandra L. Migdal, Georgia M. Davis, Maria A. Urrutia, Bonnie Albury, Cesar Zambrano, Priyathama Vellanki, Francisco J. Pasquel, Maya Fayfman, Limin Peng, Guillermo E. Umpierrez
Journal: Diabetes Care (2020)

OBJECTIVE We compared the performance of the FreeStyle Libre Pro continuous glucose monitoring (CGM) and point-of-care capillary glucose testing (POC) among insulin-treated hospitalized patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This was a prospective study in adult patients with T2D admitted to general medicine and surgery wards. Patients were monitored with POC before meals and bedtime and with CGM during the hospital stay. Study end points included differences between POC and CGM in mean daily blood glucose (BG), hypoglycemia &amp;lt;70 and &amp;lt;54 mg/dL, and nocturnal hypoglycemia. We also calculated the mean absolute relative difference (MARD), ±15%/15 mg/dL, ±20%/20 mg/dL, and ±30%/30 mg/dL and error grid analysis between matched glucose pairs. RESULTS Mean daily glucose was significantly higher by POC (188.9 ± 37.3 vs. 176.1 ± 46.9 mg/dL) with an estimated mean difference of 12.8 mg/dL (95% CI 8.3–17.2 mg/dL), and proportions of patients with glucose readings &amp;lt;70 mg/dL (14% vs. 56%) and &amp;lt;54 mg/dL (4.1% vs. 36%) detected by POC BG were significantly lower compared with CGM (all P &amp;lt; 0.001). Nocturnal and prolonged CGM hypoglycemia &amp;lt;54 mg/dL were 26% and 12%, respectively. The overall MARD was 14.8%, ranging between 11.4% and 16.7% for glucose values between 70 and 250 mg/dL and higher for 51–69 mg/dL (MARD 28.0%). The percentages of glucose readings within ±15%/15 mg/dL, ±20%/20 mg/dL, and ±30%/30 mg/dL were 62%, 76%, and 91%, respectively. Error grid analysis showed 98.8% of glucose pairs within zones A and B. CONCLUSIONS Compared with POC, FreeStyle Libre CGM showed lower mean daily glucose and higher detection of hypoglycemic events, particularly nocturnal and prolonged hypoglycemia in hospitalized patients with T2D. CGM’s accuracy was lower in the hypoglycemic range.
SO-21 Management of adverse events associated with encorafenib plus cetuximab in patients with BRAF V600E-mutant metastatic colorectal cancer (The BEACON CRC Study)
Authors: L. Velez, T. Trevino, S. Kopetz, A. Grothey, R. Yaeger, A. Gollerkeri, K. Maharry, J. Tabernero
Journal: Annals of Oncology (2020)
P-164 The role of response as a predictor of improved outcome in advanced pancreatic cancer patients treated with first-line gemcitabine plus nab-paclitaxel
Authors: M. Chiaravalli, M. Bensi, B. Di Stefano, C. Bagalà, A. Spring, M. Ribelli, M. Maratta, G. Tortora, L. Salvatore
Journal: Annals of Oncology (2020)
P-203 Restaging rectal cancer after neoadjuvant chemoradiation therapy: Is magnetic resonance imaging accurate enough?
Authors: R. Félix Soares, T. Cunha Pereira, A. Monteiro, F. Macedo, J. Paulo, M. Marques, N. Bonito, P. Jacinto, J. Ribeiro, G. Sousa
Journal: Annals of Oncology (2020)
Endoscopic submucosal dissection of large pedunculated polyps with wide stalks: a retrospective multicenter study
Authors: Hideyuki Chiba, Jun Tachikawa, Jun Arimoto, Keiichi Ashikari, Hiroki Kuwabara, Michiko Nakaoka, Toru Goto, Takuma Higurashi, Takashi Muramoto, Ken Ohata, Atsushi Nakajima
Journal: Endoscopy (2020)

Endoscopic resection of large pedunculated colorectal polyps is technically difficult, especially when the polyp is large and has such a thick stalk that it is either too difficult or impossible to resect prophylactically by a conventional snare. Here, we evaluated the feasibility of ESD for large pedunculated polyps with wide stalks. 29 patients with large pedunculated polyps that were not resectable by polypectomy or endoscopic mucosal resection were enrolled in the study. En bloc resection was achieved in 28/29 polyps. One suspended case was due to severe fibrosis with muscle retraction signs. The mean diameter of the 29 polyp heads was 39.7 (standard deviation 6.9) mm. Submucosal fibrosis was present in 16 polyps (9 mild; 7 severe). The stalks of severely fibrotic polyps were significantly thicker than those of polyps with no or mild fibrosis. The curative resection rate was 85.7 % without severe complications. ESD is feasible for the removal of large pedunculated polyps with wide stalks when conventional snare resection is difficult or impossible.
P-133 Extramural venous invasion detected with an elastin stain is a powerful predictor of cancer-specific mortality in STAGE I-IIIB resected colorectal cancer
Authors: D. Cyr, A. Akder, S. Shivji, A. Brar, S. Zerhouni, M. Brar, R. Gryfe, H. MacRae, E. Kennedy, J. Conner, R. Kirsch, C. Swallow
Journal: Annals of Oncology (2020)
Interleukin-6 receptor blockade with subcutaneous tocilizumab in severe COVID-19 pneumonia and hyperinflammation: a case–control study
Authors: Nicola Potere, Marcello Di Nisio, Donatella Cibelli, Rosa Scurti, Antonella Frattari, Ettore Porreca, Antonio Abbate, Giustino Parruti
Journal: Annals of the Rheumatic Diseases (2020)

Many patients with severe COVID-19 rapidly progress to critical disease with refractory hypoxemia requiring invasive mechanical ventilation (IMV).1 Elevated levels of C reactive protein (CRP) and interleukin-6 (IL-6), reflecting an hyperinflammatory response, identify patients at risk of progression to refractory hypoxemia and death.2 Recent evidences suggested that high-dose intravenous tocilizumab (TCZ), a humanised anti-IL-6 receptor antibody, may rapidly reduce fever and inflammatory markers, and improve oxygenation in severe to critical COVID-19.3–5 Data on the safety and efficacy of subcutaneous TCZ, already approved for the treatment of rheumatoid arthritis, are limited. The aim of this study was to compare the clinical course and outcomes of patients treated with subcutaneous TCZ on top of standard of care (SOC) with those of patients receiving SOC only.

In this retrospective case–control study, we treated with TCZ 324 mg, given as two concomitant subcutaneous injections, all consecutive patients at Pescara General Hospital, Italy between 28 March and 21 April 2020, with laboratory-confirmed COVID-19 pneumonia (involving ≥20% of lung parenchyma on chest CT), hyperinflammation (CRP ≥20 mg/dL), hypoxemia (oxygen saturation <90% on room air) requiring supplemental oxygen through nasal cannulas or mask, who had no contraindications to treatment such as bacterial or fungal infection, neutropenia or liver injury. Patients signed an informed consent for the off-label use of TCZ. We reviewed all patients hospitalised …
KIT pathway upregulation predicts dasatinib efficacy in acute myeloid leukemia
Authors: Disha Malani, Bhagwan Yadav, Ashwini Kumar, Swapnil Potdar, Mika Kontro, Matti Kankainen, Komal K. Javarappa, Kimmo Porkka, Maija Wolf, Tero Aittokallio, Krister Wennerberg, Caroline A. Heckman, Astrid Murumägi, Olli Kallioniemi
Journal: Leukemia (2020)
Abstract 10997: Impact of Atrial Fibrillation on 1-year Mortality in Transcatheter Repair of Severe Functional Mitral Regurgitation
Authors: Rakushumimarika Harada, Michinari Hieda, Yogamaya Mantha, Mayumi Fukuda-Doi, Jorge Cheirif, Mark Feldman
Journal: Circulation (2019)

Background: Percutaneous mitral valve repair with MitraClip has become a widespread therapeutic option for high-risk patients with severe mitral regurgitation. Nevertheless, limited evidence is ava...
Atherosclerotic Cardiovascular Disease Risk Stratification Based on Measurements of Troponin and Coronary Artery Calcium
Authors: Yader Sandoval, Suzette J Bielinski, Lori B Daniels, Michael J Blaha, Erin D Michos, Andrew P DeFilippis, Moyses Szklo, Christopher deFilippi, Nicholas B Larson, Paul A Decker, Allan S Jaffe
Journal: Journal of the American College of Cardiology (2020)
Inflammation and cardiovascular diseases: lessons from seminal clinical trials
Authors: Luca Liberale, Fabrizio Montecucco, Lena Schwarz, Thomas F Lüscher, Giovanni G Camici
Journal: Cardiovascular Research (2020)

Abstract Inflammation has been long regarded as a key contributor to atherosclerosis. Inflammatory cells and soluble mediators play critical roles throughout arterial plaque development and accordingly, targeting inflammatory pathways effectively reduces atherosclerotic burden in animal models of cardiovascular (CV) diseases. Yet, clinical translation often led to inconclusive or even contradictory results. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) followed by the Colchicine Cardiovascular Outcomes Trial (COLCOT) were the first two randomized clinical trials to convincingly demonstrate the effectiveness of specific anti-inflammatory treatments in the field of CV prevention, while other phase III trials—including the Cardiovascular Inflammation Reduction Trial one using methotrexate—were futile. This manuscript reviews the main characteristics and findings of recent anti-inflammatory Phase III trials in cardiology and discusses their similarities and differences in order to get further insights into the contribution of specific inflammatory pathways on CV outcomes. CANTOS and COLCOT demonstrated efficacy of two anti-inflammatory drugs (canakinumab and colchicine, respectively) in the secondary prevention of major adverse CV events (MACE) thus providing the first confirmation of the involvement of a specific inflammatory pathway in human atherosclerotic CV disease (ASCVD). Also, they highlighted the NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome-related pathway as an effective therapeutic target to blunt ASCVD. In contrast, other trials interfering with a number of inflammasome-independent pathways failed to provide benefit. Lastly, all anti-inflammatory trials underscored the importance of balancing the risk of impaired host defence with an increase in infections and the prevention of MACE in CV patients with residual inflammatory risk.
Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19
Authors: Tao Zuo, Qin Liu, Fen Zhang, Grace Chung-Yan Lui, Eugene YK Tso, Yun Kit Yeoh, Zigui Chen, Siaw Shi Boon, Francis KL Chan, Paul KS Chan, Siew C Ng
Journal: Gut (2020)

Objective Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19. Design We performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity. Results Seven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3’ vs 5’ end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3’ vs 5’ end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species Collinsella aerofaciens , Collinsella tanakaei , Streptococcus infantis , Morganella morganii , and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, Parabacteroides merdae , Bacteroides stercoris , Alistipes onderdonkii and Lachnospiraceae bacterium 1_1_57FAA . Conclusion This pilot study provides evidence for active and prolonged ‘quiescent’ GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism.
Prefixation with clip-anchored endoloop: a novel method facilitating endoscopic resection of a giant duodenal polyp with thick stalk
Authors: Xiao Hu, Xu-dan Yang, Ying-hui Zhang, Cheng-hong Li, Sheng-xi Han, Wei-hui Liu
Journal: Endoscopy (2020)

Although pretreatment of the stalk is a standard method to prevent bleeding for endoscopic removal of large pedunculated lesions [1], adequate stalk ligation is still challenging in some difficult cases [2]. In this study, we report a prefixation technique to improve endoscopic treatment of a giant duodenal polyp by reliably ligating the stalk with a clip-anchored endoloop ([Video 1]).
Inhibition of IRAK4 kinase activity improves ethanol-induced liver injury in mice
Authors: Han Wang, Hao Zhou, Quanri Zhang, Kyle L. Poulsen, Vanessa Taylor, Megan R. McMullen, Doug Czarnecki, Dhweeja Dasarathy, Minjia Yu, Yun Liao, Daniela S. Allende, Xing Chen, Lingzi Hong, Junjie Zhao, Jinbo Yang, Laura E. Nagy, Xiaoxia Li
Journal: Journal of Hepatology (2020)