tbuckley/cabot-search huggingface dataset:
Seroconversion Rates after COVID-19 Vaccination Amongst Patients with Hematologic Malignancies: Results of a Rapid Vaccination and Evaluation Program in a Minority Rich, Ethnically Diverse Inner City Cohort
Authors: Lauren C Shapiro, Radhika Gali, Astha Thakkar, Jesus D Gonzalez-Lugo, Abdul Hamid Bazarbachi, Shafia Rahman, Kith Pradhan, Karen Fehn, Michelly Abreu, Noah Kornblum, Kira Gritsman, Mendel Goldfinger, Aditi Shastri, Ioannis Mantzaris, Ira Braunschweig, Balazs Halmos, Amit Verma, Margaret McCort, Lizamarie Bachier-Rodriguez, R. Alejandro Sica
Journal: Blood (2021)
The paradox of immunosuppressants and COVID-19
Authors: Guang-Shing Cheng, Scott E. Evans
Journal: European Respiratory Journal (2021)

For millions of people, taking immunosuppressive medication to control or prevent disease is a daily reality [1]. Rheumatological disease, inflammatory lung disease, organ transplantation and graft- versus -host disease are but a few of the immune dysregulation syndromes that may require short- or long-term immunosuppressive therapy (IST). Patients taking ISTs are frequently regarded as immunocompromised, sharing risks of increased infection susceptibility with cancer patients receiving chemotherapy, those with profound neutropenia from haematological malignancies, and individuals living with HIV. In the context of the immune-mediated respiratory failure associated with coronavirus disease 2019 (COVID-19), an apparent paradox arises: can ISTs both promote and protect against severe COVID-19? Lessons learned from a large registry analysis show worse COVID-19 outcomes for patients previously exposed to glucocorticoids <https://bit.ly/306rNrk>
<i>CDKN2A</i> Deletions Define an Unfavorable Subgroup within the <i>MYD88/CD79B</i> (MCD) Subtype of Diffuse Large B-Cell Lymphoma (DLBCL) and Are Mutually Exclusive with <i>TP53</i> mutations
Authors: Adam J. Olszewski, Radwa Sharaf, Chelsea Marcus, Habibe Kurt, Lee A Albacker, Jo-Anne Vergilio, Thomas A. Ollila
Journal: Blood (2021)
Histone Hypoacetylation-Driven CD9 Repression Arrests Differentiation and Evades Immunosurveillance in Pediatric Acute Myeloid Leukemia
Authors: Yaqun Xu, Kathy Chan, Siu Ping Fok, Toni Ki Fong Man, Chi Kong Li, Kam Tong Leung
Journal: Blood (2021)
Rewriting results sections in the language of evidence
Authors: Stefanie Muff, Erlend B. Nilsen, Robert B. O’Hara, Chloé R. Nater
Journal: Trends in Ecology & Evolution (2021)

Despite much criticism, black-or-white null-hypothesis significance testing with an arbitrary P-value cutoff still is the standard way to report scientific findings. One obstacle to progress is likely a lack of knowledge about suitable alternatives. Here, we suggest language of evidence that allows for a more nuanced approach to communicate scientific findings as a simple and intuitive alternative to statistical significance testing. We provide examples for rewriting results sections in research papers accordingly. Language of evidence has previously been suggested in medical statistics, and it is consistent with reporting approaches of international research networks, like the Intergovernmental Panel on Climate Change, for example. Instead of re-inventing the wheel, ecology and evolution might benefit from adopting some of the 'good practices' that exist in other fields.
Abstract 10905: Breast Arterial Calcification as a Novel Predictor of Cardiovascular Disease Risk: A Systematic Review and Meta-Analysis
Authors: Nitesh Nerlekar, Vinay Goel, Ella Spear, William Cameron, Udit Thakur, Jasmine Chan, Nushrat Sultana, Anisha Haseeb, Adam Brown, Mark Nolan, Stephen Nicholls, Thomas Marwick
Journal: Circulation (2021)

Introduction: Mammographically detected breast arterial calcification (BAC) is purported as a surrogate marker for cardiovascular disease (CVD). We conducted a systematic review and meta-analysis to determine the prevalence of BAC and its association with CVD risk and disease. Methods: Online databases were searched until March 2021 for studies reporting BAC. Four endpoints were evaluated: (1) BAC prevalence, (2) association with CVD risk factors, (3) prevalent and incident vascular disease and (4) BAC prevalence based on estimated CVD risk. Random-effects models were used. Data was analysed as odds ratio (OR), hazard ratio (HR) or effect size (ES) obtained through data transformation for differentially reported data. A CVD-specific risk metric was calculated as the product of CVD risk factor proportion and HR risk estimate from the CAD Consortium Risk Calculator and summed for all risk factors. Meta-regression modelling with predicted BAC prevalence stratified by age was performed. Results: There were 77 studies (104,710 patients) included. Pooled BAC prevalence was 22% (95%CI: 19-25%) with cumulatively increasing prevalence annually. Significant BAC predictors were age, hypertension, diabetes, hypercholesterolemia (p&lt;0.01). BAC was associated with CAD (OR 2.65, 95%CI: 2.17-3.23, p&lt;0.01) and non-coronary vascular disease (ES 0.80, 95%CI: 0.51-1.09, p&lt;0.01). BAC associated with incident cardiovascular events (HR 1.61, 95%CI: 1.11-2.32, p=0.001). Predicted BAC prevalence associated significantly with increasing CVD risk regardless of age (Figure). Conclusions: BAC is significantly associated with prevalent and incident vascular disease affecting intimal and medial arterial beds. BAC is highly prevalent and associated with CVD risk factors individually and cumulatively. Routine assessment of BAC should be considered in screening mammography to potentially trigger CVD risk consultation.
Abstract 9289: Use of Oral Anticoagulants for Atrial Fibrillation Drops by 20% Upon Entering the Medicare Coverage Gap
Authors: Josephine L Harrington, Anthony Carnicelli, Lauren Wilson, Emily OBrien, Lesley Curtis, Sean Pokorney, Chiara Melloni, Renato D Lopes, Christopher B Granger
Journal: Circulation (2021)

Introduction: Medicare Part D beneficiaries enter a coverage gap when prescription costs for a given year exceed $3300-3700. While in this gap, patients are responsible for a substantially increased portion of their medication costs until those costs exceed $4850-5000, at which time patients exit the coverage gap. For patients with atrial fibrillation (AF), the impact of this increased cost on oral anticoagulant (OAC) medication fills (“fills”) is unknown. Hypothesis: We hypothesized that for patients with AF who enter the coverage gap, OAC fills would decrease while in the gap, particularly for non-vitamin K antagonist OACs (NOACs) due to high costs. Methods: Using the Centers for Medicare and Medicaid Services claims data from 2016-2018, we assessed OAC fills (using proportion of days covered [PDC]) in patients with AF before, during, and after the coverage gap. We compared PDC for NOACs versus warfarin by coverage gap status. Results: We analyzed OAC PDC in patients with AF across 182,192 patient-years. For patients entering the gap, median time to enter was 174 days. For patients who entered and remained in the coverage gap, median PDC dropped significantly from 0.92 to 0.76 (p=&lt;0.001) upon entering the coverage gap (Figure). For patients who entered and exited the coverage gap, PDC did not improve upon exiting the coverage gap, but rather continued to drop significantly despite having nearly full financial drug coverage (0.95 to 0.88 to 0.70; p=&lt;0.001). This pattern was similar for patients on NOACs and on warfarin. Conclusions: Upon entering the coverage gap, OAC fills decrease significantly in patients with AF. In AF patients who exit the coverage gap, OAC fills do not increase but rather continue to decrease. This pattern was consistent for NOACs and warfarin. Coverage gap status may have important and persistent impacts on OAC use in patients with AF.
Abstract 14042: Characterization of Multi-Cell-Type Engineered Heart Tissues Containing Human iPSC-Derived Cardiomyocytes, Endothelial Cells, Fibroblasts, Smooth Muscle Cells and Macrophages
Authors: Kinga M Wrona, JUlia Krause, Jutta Starbatty, Artur Ratt, Stefan Linder, Friederike Cuello, Thomas Eschenhagen, Marc N Hirt
Journal: Circulation (2021)

Introduction: Induction of a pathological type of hypertrophy in human engineered heart tissues (EHTs) has not yet been fully achieved. We hypothesized that this limitation is caused by the unicellularity of EHTs, which contain only cardiomyocytes (CMs) and lack the interactions with non-myocytes. Thus, we aimed to generate EHTs implementing five native cardiac cell types, i.e., CMs, endothelial cells (ECs), fibroblasts (Fbs), smooth muscle cells (SMCs), and macrophages (Mϕ). Methods and Results: CMs were differentiated from hiPSCs by mesodermal induction followed by inhibition of Wnt-signaling. Mesoderm progenitors were also used to differentiate ECs via VEGF stimulation. Differentiation into SMCs and Fbs required Wnt pathway activation followed by stimulation with TGFβ+bFGF or bFGF only, respectively. Finally, Mϕ differentiation required hematopoietic/myeloid specification by IL-3 and M-CSF treatment. Successful differentiation was analyzed by electron microscopy (EM) and expression profiling of hallmark genes and proteins. For instance, Mϕs exhibited high expression of myeloid markers (98.0% CD68 + , 90.9% CD14 + ) whereas Fbs showed upregulation in genes such as POSTN, DDR2, COL1A1 (all &gt;100 fold higher than iPSCs). Functionality of all cell types was demonstrated by multiple assays. For example, the native Mϕ function was demonstrated via degradation and phagocytosis assays while ECs exhibited fast and extensive tube formation in matrigel assays. Additionally, Fbs produced 4.6x more collagen after TGFβ stimulation than unstimulated controls. In effect, multi-cell-type EHTs were generated from 60% CMs, 20% ECs, 10% Mϕ, 5% SMCs and 5% Fbs. These EHTs were characterized by confocal microscopy, serial block-face scanning EM, gene expression profiling, and automated contractility measurements. Pilot experiments revealed that the addition of different cell types accelerated the development of EHTs which was associated with earlier onset of beating and shorter diameter of the EHTs. Conclusion: Successful application of cell differentiation protocols resulted in the integration of five cell types in a multi-cell-type EHT system. The full functional profile and reaction to a stress stimulus will be investigated in future experiments.
The psychometric properties of the King's Brief Interstitial Lung Disease questionnaire and thresholds for meaningful treatment response in patients with progressive fibrosing interstitial lung diseases
Authors: Surinder S. Birring, Donald M. Bushnell, Michael Baldwin, Heiko Mueller, Natalia Male, Klaus B. Rohr, Yoshikazu Inoue
Journal: European Respiratory Journal (2021)

Background There is a lack of fully validated patient-reported outcome measures for progressive fibrosing interstitial lung disease (ILD). We aimed to validate the King's Brief Interstitial Lung Disease (K-BILD) questionnaire for measuring health-related quality of life (HRQoL) in these patients. We also aimed to estimate the meaningful change threshold for interpreting stabilisation of HRQoL as a clinical end-point in progressive fibrosing ILD, where the current goal of treatment is disease stability and slowing progression. Methods This analysis evaluated data from 663 patients with progressive fibrosing ILD other than idiopathic pulmonary fibrosis from the INBUILD trial. Validation of the measurement properties was assessed for internal consistency, test–retest reliability, construct validity, known-groups validity and responsiveness. We calculated meaningful change thresholds for treatment response using anchor-based (within-patient) and distribution-based methods. Results K-BILD had strong internal consistency (Cronbach's α was 0.94 for total score, 0.88 for breathlessness and activities, 0.91 for psychological, and 0.79 for chest symptoms). The test–retest reliability intraclass correlation coefficient was 0.74 for K-BILD total score. K-BILD demonstrated weak correlations with forced vital capacity (FVC) percent predicted. Known-groups validity showed significant differences in K-BILD scores for patient groups with different disease severity based on use of supplemental oxygen or baseline FVC % pred (≤70% or &gt;70%). We estimated a meaningful change threshold of ≥ –2 units for K-BILD total score for defining patients who remain stable/improved versus those with progressive deterioration. Conclusions Our results validate K-BILD as a tool for assessing HRQoL in patients with progressive fibrosing ILD and set a meaningful change threshold of ≥ –2 units for K-BILD total score.
Trends in Late Mortality and Life Expectancy after Autologous Blood or Marrow Transplantation (BMT) Performed over Three Decades - a BMT Survivor Study (BMTSS) Report
Authors: Mukta Arora, Chen Dai, Wendy Landier, Lindsey Hageman, Jessica Wu, Elizabeth Schlichting, Arianna Siler, Erin Funk, Jessica Hicks, Nora Balas, Alysia Bosworth, Hok Sreng Te, Liton F. Francisco, Ravi Bhatia, Donna Salzman, Frederick Goldman, Stephen J Forman, Daniel J. Weisdorf, Lennie Wong, Saro H. Armenian, Smita Bhatia
Journal: Blood (2021)
Admission to hospital with acute gout is associated with a short term increased risk of major adverse cardiovascular events: a longitudinal, population-level linked health data study in Western Australia
Authors: Derrick Lopez, Johannes Nossent, Warren Raymond, David Preen, Charles Inderjeeth, Kevin Murray, Girish Dwivedi, Helen I Keen
Journal: Circulation (2021)

Introduction: Cardiovascular disease is the largest contributor to the increased mortality seen in gout. Acute inflammation, which is characteristic of gout, may have a mechanistic role in Major Ad...
Prognostic Value of Minimal Residual Disease (MRD) Among Patients with Classical Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplantation
Authors: Eleanor Taranto, Robert A. Redd, Erin Jeter, Kristin M McHugh, Jennifer R Brown, Jennifer L. Crombie, Matthew S. Davids, David C. Fisher, Arnold S. Freedman, Eric D Jacobsen, Caron Jacobson, Austin I. Kim, Ann S. LaCasce, Benjamin L. Lampson, Samuel Y. Ng, Oreofe O. Odejide, Erin Michelle Parry, Parastoo B. Dahi, Yago Nieto, Robin M. Joyce, Yi-Bin Chen, Alex F. Herrera, Philippe Armand, Reid W Merryman
Journal: Blood (2021)
Abstract 9388: The ALPACA Study, an EHR Based Analysis of the Association of Elevated Alkaline Phosphatase With Cardiovascular Events
Authors: Philip Ambery, Fe Van-den-Broek, Irena Brookes-Smith
Journal: Circulation (2021)

Alkaline phosphatase (ALP) has a key role in vascular calcification, a process implicated in cardiovascular (CV) diseases. Previous studies suggest elevated ALP is associated with increased risk of CV events, and that this association is strengthened by elevated baseline bilirubin. The risk of CV events in patients with an acute coronary syndrome (ACS) event is yet to be explored. The analysis was performed on TriNetX, a federated EHR platform of 34 large HCOs in the US. Patients who had an ACS event in 2017-2018 and had an ALP recorded ±30 days were divided by ALP below or above 79 IU/L (approximately 38,000 patients), and ALP below 70 or above 121 IU/L (approximately 12,000 patients). Patients were propensity score matched on comorbidities, laboratory measures and medications. CV outcomes, non-CV outcomes, all-cause hospital admissions and mortality were estimated at 1 year post-ACS event using the Kaplan-Meier method. Elevated ALP was associated with atrial fibrillation and heart failure events. It was also associated with renal progression and infection but not with atherothrombotic events. On top of elevated ALP, elevated bilirubin levels were a key risk driver for these outcomes. Both markers were associated with re-hospitalization and all-cause mortality. This study has confirmed that elevated ALP is strongly associated with heart failure events, re-hospitalization and mortality in ACS patients. Further research on the association between ALP, bilirubin and cardiovascular outcomes is warranted.
Identification By Whole Exome Sequencing of the Molecular Defect in a Novel Gene Related to Glycosylation in Two Unrelated Families with Syndromic Macrothrombocytopenia
Authors: Ana Marín-Quílez, Elena Vuelta, Sandra Santos-Mínguez, Cristina Miguel-García, Pedro Ruíz-Sala, Veronica Palma-Barqueros, Lorena Díaz-Ajenjo, Inmaculada Serramito-Gómez, Maria Jesús Peñarrubia, Emilia Pardal, Daisy Castiñeiras-Ramos, José Ramón González-Porras, Jose Rivera, Rocio Benito, Jesus Maria Hernández-Rivas, Ignacio García-Tuñón, Jose Maria Bastida
Journal: Blood (2021)
Matching-Adjusted Indirect Comparisons of Efficacy Outcomes in Patients with Relapsed and Refractory Multiple Myeloma for Idecabtagene Vicleucel (KarMMa) Versus Selinexor Plus Dexamethasone (STORM Part 2) and Belantamab Mafodontin (DREAMM-2): Updated Analysis with Longer Follow-up
Authors: Paula Rodríguez-Otero, Ali Mojebi, Dieter Ayers, Devender Dhanda, James Farrell, Faith E. Davies, Michel Delforge, Katja Weisel, Kevin Towle, Tom Marshall, Clyde Caisip, Shannon Cope
Journal: Blood (2021)
Abstract 10117: Reactivity Of Myocardial Contractility To Afterload Effects During Peripheral Veno-arterial Extracorporeal Membrane Oxygenation
Authors: Pauline Yeung Ng, Sin Kwan Tammy Ma, April Ip, Shu Fang, Alfred Sai Kuen Wong, Chun Wai Ngai, Wai Ming Chan, Wai Ching Sin
Journal: Circulation (2021)

Introduction: Peripheral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) poses increased afterload to the injured heart. The reactivity of myocardial contractility to ECMO blood flow during various phases of acute myocardial dysfunction has not been examined. Hypothesis: We hypothesized that myocardial contractility is more reactive to the afterload effects of peripheral V-A ECMO during the acute stage of myocardial dysfunction. Methods: Adult patients who were supported by peripheral V-A ECMO between April 2019 and October 2020 were recruited. Serial hemodynamic and cardiac performance parameters were measured by TTE within 48 hours after initiation of V-A ECMO (“acute phase”) and upon weaning (“delayed phase”). Measurements were obtained at 100%, 120%, and 50% of ECMO target blood flow. Results: A total of 30 patients were included, 22 (71%) were male, and the mean±SD age was 54±13 years. The main indications of ECMO were myocardial infarction (19 patients, 63%) and myocarditis (5, 17%). TTE was performed on a median of day 1 (1-1) (n=30, “acute phase”) and day 4.5 (3-6) (n=24, “delayed phase”) after initiation of ECMO. Left ventricular contractility was reactive to afterload effects from V-A ECMO in both the acute and delayed phases, with an improvement in LVEF during ECMO flow reduction from 21.5 to 30.9% (p&lt;0.001) and 34.5 to 41.7% (p=0.002), respectively. The change in LVEF was similar in the acute phase compared with the delayed phase when considering the whole cohort [median (IQR) change in LVEF: 8.88 (5.26 - 13.7)% vs 6.12 (0.64 - 15.60)%, p=0.38]. Of the 24 patients who had a TTE during the delayed phase, 16 (66.7%) had myocardial recovery and were weanable from ECMO support. The reactivity of LVEF to ECMO blood flow was similar in the patients who were weanable compared with patients who were not weanable [median (IQR) change in LVEF: 10.21 (2.61 - 16.21)% vs 3.20 (-2.13 - 6.79)%, p=0.14]. Conclusions: In conclusion, we demonstrated that the reactivity of left ventricular contractility to afterload effects of V-A ECMO was not significantly different at different stages of acute myocardial dysfunction. Future studies should examine the predictive value and clinical utility of these echocardiographic measurements in patients on V-A ECMO.
Abstract 12224: Predictive Power and Value of a CAD Polygenic Risk Score in Primary Prevention Based on Age and Clinical Risk
Authors: Nicholas A Marston, James Pirruccello, Giorgio Melloni, Frederick Kamanu, Carolina Roselli, Krishna Aragam, Adam Butterworth, Steven A Lubitz, Patrick T Ellinor, Marc S Sabatine, Christian T Ruff
Journal: Circulation (2021)

Background: The clinical utility of polygenic risk scores (PRS) for CAD has not yet been established. We investigated the ability of a CAD PRS to potentially guide statin initiation after accounting for age and clinical risk. Methods: We performed a prospective cohort study in the UK Biobank that included all individuals without a history of CAD and who were not on lipid-lowering therapy. The CAD PRS was comprised of 241 genome-wide significant SNPs. Genetic risk categories were defined as low (bottom 20%), intermediate, and high (top 20%). HRs were calculated as a function of age. Next, 10-year ASCVD risk score was used to classify individuals as low, borderline, intermediate, or high risk. Each ASCVD risk group was further stratified by genetic risk to determine whether genetics could reclassify individuals to help guide decisions regarding statin initiation with more precision. ASCVD events were defined as incident clinical CAD (including MI), stroke, or CV death. Results: The 333,245 patients included in this study were ages 40-74 years (avg 57) and 57% were female. Over the 10-yr follow-up, there were 4,552 MIs. The CAD PRS significantly predicted MI in all age groups but had significantly stronger risk prediction at younger ages (p-int &lt;0.001) ( Figure, A ). This gradient of risk was especially pronounced under 50 years of age, where those with high PRS approached a 6-fold increased risk of MI compared with those in the low PRS category. When CAD PRS testing was added to the 71,534 patients &lt;50 years old, 20% of borderline risk patients were reclassified into intermediate risk, warranting initiation of statin therapy to reduce LDL-C, and 20% of borderline and intermediate risk patients were reclassified as low risk, thus not warranting therapy ( Figure, B ). Conclusion: The predictive ability of a CAD PRS is especially strong in individuals under the age of 50 and can be used to identify more precisely who should be initiated on statin therapy.
Abstract 9404: Detecting Sars-cov-2 Orf3a and E Ion Channel Activity in Covid-19 Blood Samples
Authors: Hangang Yu, Gina Sizemore, Katy Smoot, Peter Perrotta
Journal: Circulation (2021)

Introduction: SARS-CoV-2 has been found in the heart of COVID-19 patients. It is unclear how the virus passes from the upper respiratory tract to the myocardium. Hypothesis: SARS-CoV-2 is present in the blood of COVID-19 infected patients. Methods: We targeted two viropotins, Orf3a and E, in SARS-CoV-2. Orf3a and E form non-voltage-gated ion channels. A combined fluorescence potassium ion assay with three channel modulators (4-aminopyridine, emodin-Orf3a channel blocker, gliclazide-E channel blocker) was developed to detect SARS-CoV-2 Orf3a/E channel activity. In blood samples, we subtracted the fluorescence signals in the absence and presence of emodin/gliclazide to detect Orf3a and E channel activity. Results: In lentivirus spiked samples, we detected significant channel activity of Orf3a/E based on increase in fluorescence induced by 4-aminopyridine, and this increase in fluorescence was inhibited by emodin and gliclazide. In 18 antigen/PCR positive samples, our test results found 15 are positive, demonstrating 83.3% concordance. In 24 antigen/PCR negative samples, our test results found 21 are negative, showing 87.5% concordance. Conclusions: We developed a cell-free, rapid, and high-throughput test that can detect Orf3a/E channel activity of SARS-CoV-2 in blood samples from COVID-19 infected individuals, which provides a likely explanation that the virus spreads to the heart via blood circulation.
Pre-Clinical Development of a Highly Efficient TALEN ®-Based Correction of the β-Globin Gene in Patient-Derived Hematopoietic Stem and Progenitor Cells (HSPCs) to Treat Sickle Cell Disease
Authors: Arianna Moiani, Patrick Hong, Gil Letort, Sabrina Lizot, Alexa Chirinos, Sonal Temburni-Blake, Sara Nik, Louisa Mayer, Sophie Leduc, Noemie Pinard, Chloe Foray, Alex Boyne, Selena Kazancioglu, Giacomo Frati, Tristan Felix, Anne Chalumeau, Annarita Miccio, Mathilde Dusseaux, Agnès Gouble, Mark G. Frattini, Carrie Brownstein, Aymeric Duclert, Cecile Shiffer-Mannoui, Alexandre Juillerat, Philippe Duchateau, Julien Valton
Journal: Blood (2021)