tbuckley/cabot-search huggingface dataset:
Reduction in Late Mortality after Autologous Blood or Marrow Transplantation (autoBMT) in Childhood - a Report from the Blood or Marrow Transplant Survivor Study-2 (BMTSS-2)
Authors: Anna Sallfors Holmqvist, Yanjun Chen, Jessica Wu, Lindsey Hageman, Liton F. Francisco, Mariel Parman, Michelle Kung, Emily Ness, Kevin D. Battles, Jeanette Falck Winther, Joseph Rosenthal, Ravi Bhatia, Donna Salzman, Stephen J. Forman, Daniel J. Weisdorf, Saro H. Armenian, Mukta Arora, Smita Bhatia
Journal: Blood (2017)
Effect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report
Authors: P Horby, W S Lim, J Emberson, M Mafham, J Bell, L Linsell, N Staplin, C Brightling, A Ustianowski, E Elmahi, B Prudon, C Green, T Felton, D Chadwick, K Rege, C Fegan, L Chappell, S Faust, T Jaki, K Jeffery, A Montgomery, K Rowan, E Juszczak, K Baillie, R Haynes, M Landray
Journal: New England Journal of Medicine (2020)

Background: Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death.
Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality.
Results: 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14).
Conclusions: In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.
Abstract 14036: Impaired Diastolic Reserve During Exercise in Children After Anthracycline Therapy With Normal Left Ventricular Ejection Fraction
Authors: Sachie Kaneko, Edythe B Tham, Michael D Nelson, Maria Spavor, Nee S Khoo, Andrew S Mackie, Jeffrey F Smallhorn, Richard B Thompson, Mark J Haykowsky
Journal: Circulation (2011)

Background Anthracycline cardiotoxicity is a late complication of chemotherapy for childhood cancer and has an impact on exercise performance. We evaluated left ventricular systolic and diastolic f...
Abstract 12128: Lost to Follow-up Bias May Commonly Alter Primary Outcome in Cardiovascular Randomised Trials
Authors: Lucas C Fong, Tom Ford, Bruno da Costa, Peter Juni, Colin Berry
Journal: Circulation (2019)

Introduction: Lost to follow-up (LTFU) is common in trials. However, its impact on trial estimates is not evaluated. We study the extent, reporting and handling of LTFU data in cardiovascular rando...
Low physical functioning and impaired performance of activities of daily life in COVID-19 patients who survived hospitalisation
Authors: Stefano Belli, Bruno Balbi, Ilaria Prince, Davide Cattaneo, Francesca Masocco, Sergio Zaccaria, Luca Bertalli, Francesco Cattini, Arianna Lomazzo, Francesca Dal Negro, Marica Giardini, Frits M.E. Franssen, Daisy J.A. Janssen, Martijn A. Spruit
Journal: European Respiratory Journal (2020)

<b>About</b><b>half of post-COVID-19 patients had severe impairments in physical functioning and during activities of daily living at discharge home, providing a clear rationale to study the safety and efficacy of rehabilitative interventions in these patients</b>https://bit.ly/3hJvXJa
Alcohol Use and Co-Use of Other Substances Among Pregnant Females Aged 12–44 Years — United States, 2015–2018
Authors: Lucinda J. England, Carolyne Bennett, Clark H. Denny, Margaret A. Honein, Suzanne M. Gilboa, Shin Y. Kim, Gery P. Guy, Emmy L. Tran, Charles E. Rose, Michele K. Bohm, Coleen A. Boyle
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Drinking alcohol during pregnancy can cause fetal alcohol spectrum disorders, including birth defects, behavioral disorders, and impaired cognitive development (1). Little is known about the co-use of other substances by females who drink during pregnancy. CDC used 2015-2018 data from the National Survey on Drug Use and Health (NSDUH) to estimate the overall and trimester-specific prevalence of self-reported drinking in the past 12 months, current drinking, and binge drinking, overall and by trimester, and the co-use of other substances among pregnant females aged 12-44 years. Past drinking (12 months) was reported by 64.7% of pregnant respondents. Current drinking (at least one drink in the past 30 days) was reported by 19.6% of respondents who were in their first trimester of pregnancy and 4.7% of respondents who were in their second or third trimester. Binge drinking (consuming four or more drinks on at least one occasion in the past 30 days) was reported by 10.5% of first trimester respondents and 1.4% of second or third trimester respondents. Overall, 38.2% of pregnant respondents who reported current drinking also reported current use of one or more other substances. The substances used most with alcohol were tobacco and marijuana. Self-reported drinking prevalence was substantially lower among second or third trimester respondents than among first trimester respondents. The American College of Obstetricians and Gynecologists (ACOG) recommends alcohol use and substance use disorders screening for all females seeking obstetric-gynecologic care and counseling patients that there is no known safe level of alcohol use during pregnancy (2).
Pathological findings in suspected cases of e-cigarette, or vaping, product use-associated lung injury (EVALI): a case series
Authors: Sarah Reagan-Steiner, Joy Gary, Eduard Matkovic, Jana M Ritter, Wun-Ju Shieh, Roosecelis B Martines, Angela K Werner, Ruth Lynfield, Stacy Holzbauer, Hannah Bullock, Amy M Denison, Julu Bhatnagar, Brigid C Bollweg, Mitesh Patel, Mary E Evans, Brian A King, Dale A Rose, Grant T Baldwin, Christopher M Jones, Vikram Krishnasamy, Peter A Briss, David N Weissman, Dana Meaney-Delman, Sherif R Zaki, Tara Jatlaoui, Emilia Koumans, Emily Kiernan, Emily Petersen, Mateusz P. Karwowski, Liza Valentin-Blasini, Benjamin C. Blount, Kristin J. Cummings, Isaac Ghinai, Kenneth Feder, Eden V. Wells, George Turabelidze, Paul Byers, Lauren J. Tanz, Kristen A. Navarette, Kirtana Ramadugu, Courtney Dewart, Jeffrey Miller, Kelly Squires, Lily Marsden, Cheryl A. Fields
Journal: The Lancet Respiratory Medicine (2020)
Disparities in United States hospitalizations for serious infections in patients with and without opioid use disorder: A nationwide observational study
Authors: June-Ho Kim, Danielle R. Fine, Lily Li, Simeon D. Kimmel, Long H. Ngo, Joji Suzuki, Christin N. Price, Matthew V. Ronan, Shoshana J. Herzig
Journal: PLoS Medicine (2020)

Background Patients with opioid use disorder (OUD) who are hospitalized for serious infections requiring prolonged intravenous antibiotics may face barriers to discharge, which could prolong hospital length of stay (LOS) and increase financial burden. We investigated differences in LOS, discharge disposition, and charges between hospitalizations for serious infections in patients with and without OUD. Methods and findings We utilized the 2016 National Inpatient Sample—a nationally representative database of all discharges from US acute care hospitals. The population of interest was all hospitalizations for infective endocarditis, epidural abscess, septic arthritis, or osteomyelitis. The exposure was OUD, and the primary outcome was LOS until discharge, assessed by using a competing risks analysis to estimate adjusted hazard ratios (aHRs). Adjusted odds ratio (aOR) of discharge disposition and adjusted differences in hospital charges were also reported. Of 95,470 estimated hospitalizations for serious infections (infective endocarditis, epidural abscess, septic arthritis, and osteomyelitis), the mean age was 49 years and 35% were female. 46% had Medicare (government-based insurance coverage for people age 65+ years), and 70% were non-Hispanic white. After adjustment for potential confounders, OUD was associated with a lower probability of discharge at any given LOS (aHR 0.61; 95% CI 0.59–0.63; p < 0.001). OUD was also associated with lower odds of discharge to home (aOR 0.38; 95% CI 0.33–0.43; p < 0.001) and higher odds of discharge to a post-acute care facility (aOR 1.85; 95% CI 1.57–2.17; p < 0.001) or patient-directed discharge (also referred to as "discharge against medical advice") (aOR 3.47; 95% CI 2.80–4.29; p < 0.001). There was no significant difference in average total hospital charges, though daily hospital charges were significantly lower for patients with OUD. Limitations include the potential for unmeasured confounders and the use of billing codes to identify cohorts. Conclusions Our findings suggest that among hospitalizations for some serious infections, those involving patients with OUD were associated with longer LOS, higher odds of discharge to post-acute care facilities or patient-directed discharge, and similar total hospital charges, despite lower daily charges. These findings highlight opportunities to improve care for patients with OUD hospitalized with serious infections, and to reduce the growing associated costs.
Abstract B02: 5-Hydroxymethylcytosine profiles in circulating cell-free DNA are biomarkers of disease burden in children with neuroblastoma
Authors: Mark A. Applebaum, Erin K. Barr, Jason Karpus, Meritxell Oliva, Alexandre Chlenski, Helen R. Salwen, Emma Wilkinson, Marija Dobratic, Elizabeth A. Sokol, Barbara E. Stranger, Chuan He, Susan L. Cohn
Journal: Cancer Research (2020)

Abstract Background: 5-Hydroxymethylcytosine (5-hmC) is an epigenetic marker of open chromatin and active gene expression. The level of 5-hmC expression serves as a biomarker in adults with cancer, and we recently demonstrated the prognostic significance of tumor whole-genome 5-hmC profiling in children with neuroblastoma. Here, we used Nano-hmC-Seal technology to profile 5-hmC in circulating cell-free DNA (cfDNA) in blood samples from patients with neuroblastoma and age-matched healthy children. Methods: Plasma was collected from 32 children with neuroblastoma at various time points during therapy and 34 well children. 5-hmC sequencing was performed using 100ng of cfDNA extracted from plasma. Metastatic disease burden was classified as high, moderate, low, or none based on Curie MIBG scores, the percentage of tumor cells in bone marrow samples, and/or measurable disseminated soft tissue disease. Results: One hundred cfDNA 5-hmC profiles were generated from 27 high-risk, 3 intermediate-risk, and 2 low-risk patients and 34 well controls. Hierarchical clustering based on 5-hmC levels of 347 genes separated the samples into three main clusters corresponding to high, moderate, and low/no disease burden in the bone, bone marrow, and/or soft tissue. Using functional gene pathways, two subsets of patients within the low/no cluster were revealed that correlated with low tumor burden or no clinically detectable metastatic disease (sensitivity 70%, specificity 76.9%). 5-hmC profiles tracked closely with changes in disease status in 15 patients with serial samples. Samples from patients with a detectable tumor burden had genes with elevated 5-hmC in pathways of neuronal stem cell maintenance and the epigenetic regulatory complexes PRC2 and CTCF/cohesion. Conclusions: cfDNA 5-hmC profiles correlate with disease burden in children with neuroblastoma and may serve as sensitive biomarkers of treatment response. Analysis of transcriptional networks regulated by these epigenomic modifications may lead to a deeper understanding of the pathways that drive resistance to treatment. Citation Format: Mark A. Applebaum, Erin K. Barr, Jason Karpus, Meritxell Oliva, Alexandre Chlenski, Helen R. Salwen, Emma Wilkinson, Marija Dobratic, Elizabeth A. Sokol, Barbara E. Stranger, Chuan He, Susan L. Cohn. 5-Hydroxymethylcytosine profiles in circulating cell-free DNA are biomarkers of disease burden in children with neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B02.
Medical Marijuana, Recreational Cannabis, and Cardiovascular Health: A Scientific Statement From the American Heart Association
Authors: Robert L. Page, Larry A. Allen, Robert A. Kloner, Colin R. Carriker, Catherine Martel, Alanna A. Morris, Mariann R. Piano, Jamal S. Rana, Jorge F. Saucedo
Journal: Circulation (2020)

Cannabis, or marijuana, has potential therapeutic and medicinal properties related to multiple compounds, particularly Δ-9-tetrahydrocannabinol and cannabidiol. Over the past 25 years, attitudes toward cannabis have evolved rapidly, with expanding legalization of medical and recreational use at the state level in the United States and recreational use nationally in Canada and Uruguay. As a result, the consumption of cannabis products is increasing considerably, particularly among youth. Our understanding of the safety and efficacy of cannabis has been limited by decades of worldwide illegality and continues to be limited in the United States by the ongoing classification of cannabis as a Schedule 1 controlled substance. These shifts in cannabis use require clinicians to understand conflicting laws, health implications, and therapeutic possibilities. Cannabis may have therapeutic benefits, but few are cardiovascular in nature. Conversely, many of the concerning health implications of cannabis include cardiovascular diseases, although they may be mediated by mechanisms of delivery. This statement critically reviews the use of medicinal and recreational cannabis from a clinical but also a policy and public health perspective by evaluating its safety and efficacy profile, particularly in relationship to cardiovascular health.
OP0141 #X00A0; CD28 AS A POTENTIAL THERAPEUTIC TARGET FOR GIANT CELL ARTERITIS
Authors: Ryu Watanabe, Hui Zhang, Gerald Berry, Steven Nadler, Jörg Goronzy, Cornelia Weyand
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Giant cell arteritis (GCA) is a granulomatous vasculitis of medium and large arteries. In GCA-affected arteries, vascular wall is destroyed by tissue-infiltrating CD4 T cells and macrophages, which leads to intramural neoangiogenesis, intimal hyperplasia and luminal occlusion. <h3>Objectives</h3> This study aimed to examine how CD28 signaling plays a role in vasculitis induction and maintenance and which pathogenic processes are dependent on CD28-mediated T-cell activation. <h3>Methods</h3> We engrafted human arteries into immunodeficient NSG mice and induced vasculitis by transferring GCA immune cells. Human artery-NSG chimeras were treated with anti-CD28 domain antibody or control Ab. Using tissue transcriptome analysis, immunohistochemistry, flow cytometry and immuno-metabolic analysis, treatment effects were examined in vivo and in vitro. <h3>Results</h3> Treating such humanized mice with an anti-CD28 domain antibody profoundly reduced tissue-infiltrating T-cells and effectively suppressed vasculitis. Mechanistic studies revealed that CD28 regulated AKT signaling, T-cell proliferation and differentiation of IFN-γ and IL-21-producing effector T-cells. Blocking CD28 signaling disrupted T-cell metabolic fitness; particularly, glucose utilization. Expression of the glucose transporter Glut1 and of glycolytic enzymes as well as mitochondrial oxygen consumption all rely on CD28 signaling. CD28 blockade effectively suppressed vessel wall remodeling processes such as adventitial microvessel formation and intimal hyperplasia as well as induction and maintenance of CD4<sup>+</sup>CD103<sup>+</sup> tissue-resident memory T cells. <h3>Conclusion</h3> CD28 stimulation provides a metabolic signal required for pathogenic effector functions in GCA, implicating CD28 signaling as a promising therapeutic target. <h3>References</h3> [1] MMP (Matrix Metalloprotease)-9-Producing Monocytes Enable T Cells to Invade the Vessel Wall and Cause Vasculitis. [2] Watanabe R, Maeda T, Zhang H, Berry GJ, Zeisbrich M, Brockett R, Greenstein AE, Tian L, Goronzy JJ, Weyand CM. [3] Circ Res. 2018 Aug 31;123(6):700-715. [4] Inhibition of JAK-STAT Signaling Suppresses Pathogenic Immune Responses in Medium and Large Vessel Vasculitis. [5] Zhang H, Watanabe R, Berry GJ, Tian L, Goronzy JJ, Weyand CM. Circulation. 2018 May 1;137(18):1934-1948. <h3>Acknowledgement</h3> This work was supported by a sponsored research agreement with Bristol-Myers Squibb. <h3>Disclosure of Interests</h3> Ryu Watanabe: None declared, Hui Zhang: None declared, Gerald Berry: None declared, Steven Nadler Employee of: Bristol-Myers Squibb, Jörg Goronzy: None declared, Cornelia Weyand: None declared
Effect of COVID-19 on First-Time Acute Stroke and Transient Ischemic Attack Admission Rates and Prognosis in Denmark
Authors: Jawad H. Butt, Emil L. Fosbøl, Lauge Østergaard, Adelina Yafasova, Charlotte Andersson, Morten Schou, Thomas A. Gerds, Matthew Phelps, Christina Kruuse, Gunnar H. Gislason, Christian Torp-Pedersen, Lars Køber
Journal: Circulation (2020)

On March 13, 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the novel coronavirus disease 2019 (COVID-19) and reprioritized limited healthcare resources.However, this strategy may have a detrimental effect on medical care to patients with other acute conditions such as stroke and may increase the reluctance of patients with symptoms to contact emergency medical services.To shed light on the possible collateral effects of a lockdown strategy and reprioritization within the healthcare system, we performed a nationwide cohort study to investigate stroke and transient ischemic attack (TIA) admission rates and prognosis in Denmark during the COVID-19 pandemic.Data from several nationwide administrative registries were obtained, and they have been described previously. 1 The study population comprised every Danish citizen in 2 periods: (1) a combined period of January 2 to May 8 (2017-2019), and (2) January 2 to May 7, 2020.Weekly incidence rates and incidence rates before and after March 13 of first-time stroke/TIA admissions, overall and according to subtypes, in the 2 periods were compared with unadjusted Poisson regression.Furthermore, mortality rates among patients admitted with stroke/TIA, overall and according to subtypes, before and after March 13, were compared with the use of unadjusted Cox regression.The study is approved by the Capital Region of Denmark (approval P-2019-191) in accordance with the General Data Protection Regulation.Before March 13, an average of 2862 patients were admitted with stroke/TIA in 2017 to 2019 compared with 2954 patients in 2020.After March 13, the corresponding numbers were 2323 and 2029, respectively.The admission rates of stroke/TIA were significantly lower during the first weeks of lockdown in 2020 but returned to a rate similar to that observed in 2017 to 2019 toward the end of the study period (Figure [A]).However, results differed according to subtypes.Although the admission rates of ischemic stroke and TIA were significantly lower during the first weeks of lockdown in 2020 before returning to rates similar to those observed in 2017 to 2019 toward the end of the study period, the admission rate of hemorrhagic stroke was not significantly different after lockdown in 2020 compared with 2017 to 2019 (Figure [B through D]).These results were consistent regardless of sex and age.In addition, expanding the study population to patients with a history of stroke/TIA yielded similar findings.The mortality rates among patients admitted with stroke/TIA, overall and according to subtypes, before and after March 13 were not significantly different in 2020 compared with 2017 to 2019 (Figure [E]).3][4] The reasons for the significant decline in stroke admissions after lockdown are unclear.
The Expanding Role of the COX Inhibitor/Opioid Receptor Agonist Combination in the Management of Pain
Authors: Giustino Varrassi, Cheng Teng Yeam, Martina Rekatsina, Joseph V. Pergolizzi, Panagiotis Zis, Antonella Paladini
Journal: Drugs (2020)

Pain management in both outpatient and inpatient settings demands a multidisciplinary approach entailing medical, physical and psychological therapies. Among these, multimodal analgesic regimens stand out as a promising treatment options. Cyclo-oxygenase (COX) inhibitor/opioid receptor agonist combinations hold great potential as effective pillars in the multimodal pain management by providing adequate analgesia with fewer safety risks due to COX inhibitors' opioid-sparing effect. Thus, these combinations, either freely or in fixed-dose formulation, offer a feasible option for the prescribing clinicians who seek to maximise therapeutic effect while simultaneously minimise adverse effects. The selection of the appropriate non-steroidal anti-inflammatory drug (NSAID) and opioid agent at optimal doses is essential. It should be tailored to the patients' analgesic necessities, and his/her gastrointestinal and cardiovascular risk, and potential concurrent aspirin use. Moreover, it should allow for addiction risk and the potential opioid-induced bowel dysfunction and constipation. To ensure an optimal match between the characteristics of the patient and the properties of the chosen medication, and to guide adequate and well-tolerated treatment decisions, it is of paramount importance to expand clinicians' knowledge of the currently available COX inhibitor/opioid receptor agonist combinations. This invited narrative review deals with the literature evidence covering the components of multimodal opioid-sparing analgesic regimens. Also, it provides insights into the clinically relevant choice criteria to ensure a patient-tailored analgesia.
Unraveling the role of MUC5B in idiopathic interstitial pneumonias (IIPs)
Authors: Evgenia Dobrinskikh, Ivana V Yang
Journal: Thorax (2020)

ABSTRACT  As many as 22 of the 45 coral species on the Florida Reef Tract are currently affected by stony coral tissue loss disease (SCTLD). The ongoing disease outbreak was first observed in 2014 in Southeast Florida near Miami and as of early 2019 has been documented from the northernmost reaches of the reef tract in Martin County down to Key West. We examined the microbiota associated with disease lesions and apparently healthy tissue on diseased colonies of Montastraea cavernosa, Orbicella faveolata, Diploria labyrinthiformis, and Dichocoenia stokesii. Analysis of differentially abundant taxa between disease lesions and apparently healthy tissue identified five unique amplicon sequence variants enriched in the diseased tissue in three of the coral species, namely an unclassified genus of Flavobacteriales and sequences identified as Fusibacter (Clostridiales), Planktotalea (Rhodobacterales), Algicola (Alteromonadales), and Vibrio (Vibrionales). In addition, several groups of likely opportunistic or saprophytic colonizers such as Epsilonbacteraeota, Patescibacteria, Clostridiales, Bacteroidetes, and Rhodobacterales were also enriched in SCTLD disease lesions. This work represents the first microbiological characterization of SCTLD, as an initial step toward identifying the potential pathogen(s) responsible for SCTLD.