tbuckley/cabot-search huggingface dataset:
Cost Utility of Lifelong Immunoglobulin Replacement Therapy vs Hematopoietic Stem Cell Transplant to Treat Agammaglobulinemia
Authors: Di Sun, Jennifer R. Heimall, Matthew J. Greenhawt, Nancy J. Bunin, Marcus S. Shaker, Neil Romberg
Journal: JAMA Pediatrics (2021)

Lifelong immunoglobulin replacement therapy (IRT) is standard-of-care treatment for congenital agammaglobulinemia but accrues high annual costs ($30 000-$90 000 per year) and decrements to quality of life over patients' life spans. Hematopoietic stem cell transplant (HSCT) offers an alternative 1-time therapy, but has high morbidity and mortality.To evaluate the cost utility of IRT vs matched sibling donor (MSD) and matched unrelated donor (MUD) HSCT to treat patients with agammaglobulinemia in the US.This economic evaluation used Markov analysis to model the base-case scenario of a patient aged 12 months with congenital agammaglobulinemia receiving lifelong IRT vs MSD or MUD HSCT. Costs, probabilities, and quality-of-life measures were derived from the literature. Microsimulations estimated premature deaths for each strategy in a virtual cohort. One-way sensitivity and probabilistic sensitivity analyses evaluated uncertainty around parameter estimates performed from a societal perspective over a 100-year time horizon. The threshold for cost-effective care was set at $100 000 per quality-adjusted life-year (QALY). This study was conducted from 2020 across a 100-year time horizon.Immunoglobulin replacement therapy vs MSD or MUD HSCT for treatment of congenital agammaglobulinemia.The primary outcomes were incremental cost-effectiveness ratio (ICER) expressed in 2020 US dollars per QALY gained and premature deaths associated with each strategy.In this economic evaluation of patients with congenital agammaglobulinemia, lifelong IRT cost more than HSCT ($1 512 946 compared with $563 776 [MSD] and $637 036 [MUD]) and generated similar QALYs (20.61 vs 17.25 [MSD] and 17.18 [MUD]). Choosing IRT over MSD or MUD HSCT yielded ICERs of $282 166 per QALY gained over MSD and $255 633 per QALY gained over MUD HSCT, exceeding the US willingness-to-pay threshold of $100 000/QALY. However, IRT prevented at least 2488 premature deaths per 10 000 microsimulations compared with HSCT. When annual IRT price was reduced from $60 145 to below $29 469, IRT became the cost-effective strategy. Findings remained robust in sensitivity and probabilistic sensitivity analyses.In the US, IRT is more expensive than HSCT for agammaglobulinemia treatment. The findings of this study suggest that IRT prevents more premature deaths but does not substantially increase quality of life relative to HSCT. Reducing US IRT cost by 51% to a value similar to IRT prices in countries implementing value-based pricing may render it the more cost-effective strategy.
Survival Analysis of Patients with T-Cell Lymphoma or T-Cell Large Granular Leukemia and Concomitant Plasma Cell Dyscrasias
Authors: Zachary Braunstein, Miguel Ruiz, Eric McLaughlin, Naresh Bumma, Don M Benson, Srinivas Devarakonda, Maria Chaudhry, Abdullah Khan, Francesca Cottini, John C. Reneau, Pierluigi Porcu, Anjali Mishra, Ashley E. Rosko, Jonathan E Brammer
Journal: Blood (2021)
Treatment-Free Remission in Patients with Chronic Myeloid Leukemia Following the Discontinuation of Tyrosine Kinase Inhibitors
Authors: Fadi Haddad, Hagop Kantarjian, Elias J. Jabbour, Ghayas C. Issa, Guillermo Garcia-Manero, Farhad Ravandi, Marina Konopleva, Alessandra Ferrajoli, Tapan M. Kadia, Naveen Pemmaraju, Koichi Takahashi, Yesid Alvarado, Musa Yilmaz, Gautam Borthakur, Courtney D. DiNardo, Nitin Jain, Naval Daver, Nicholas J. Short, Sherry A. Pierce, Jorge E. Cortes, Koji Sasaki
Journal: Blood (2021)
Abstract PO-125: The role of KDM6A in pancreatic cancer immune microenvironment
Authors: Lin Jin, Jing Yang, Zhujun Yi, Hong S. Kim, Feng Tian, Jiaqi Shi
Journal: Cancer Research (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States, with a 10% 5-year survival rate. Immunosuppressive myeloid cells, including tumor-associated neutrophils (TANs), contribute to tumor development and treatment resistance. Lysine (K)-specific demethylase 6A (KDM6A) is one of the most frequently mutated epigenetic genes and a tumor suppressor in PDAC. However, the molecular mechanisms by which KDM6A contributes to PDAC development and whether KDM6A impacts the tumor immune microenvironment are unknown. This study established a genetically engineered pancreas-specific Kdm6a-knockout Ptf1aCre;LSL-KrasG12D/+;LSL-p53R172H/+ (KPC) PDAC mouse model to investigate the influence of KDM6A loss on PDAC development and tumor immune microenvironment. We found that KDM6A loss accelerated PDAC progression and increased metastases. Pancreata of mice with Kdm6a deficiency developed aggressive undifferentiated PDACs. Additionally, KDM6A loss led to increased infiltration of TANs and neutrophil extracellular traps (NETs) formation. Mechanistically, we used Bru-seq technology to investigate the impact of KDM6A on nascent RNA transcription. We demonstrated that many chemotactic cytokines related to neutrophil recruitment, specifically CXCL1, were upregulated in KDM6A-knockout PDAC cells. We further confirmed increased CXCL1 mRNA and protein levels in KDM6A-deficient human and mouse PDAC cells. In addition, immunohistochemical staining also confirmed the upregulated CXCL1 expression in both human and murine PDAC cells with KDM6A loss. TANs were found to express CXCR2, the receptor of CXCL1, by immunofluorescent analysis. To further confirm that cancer cells with KDM6A loss can attract neutrophils in vitro, we performed chemotaxis assays using both human neutrophils derived from PLB-985 cells and mouse primary neutrophils isolated from bone marrow and conditioned media from KDM6A- knockout or knockdown PDAC cells. We found that PDAC cells with KDM6A loss promoted neutrophil recruitment in vitro compared to KDM6A-retained PDAC cells. Furthermore, the CXCL1 neutralizing antibody reversed the chemotactic property of KDM6A-deficient PDAC cells, confirming that CXCL1 is the primary chemokine mediating the neutrophil recruitment. In summary, these findings shed light on the mechanism by which KDM6A loss promotes PDAC development, regulates tumor immune microenvironment, and suggests that the CXCL1-CXCR2 axis may be a candidate target for the treatment of PDAC, especially those with KDM6A mutations. Citation Format: Lin Jin, Jing Yang, Zhujun Yi, Hong S. Kim, Feng Tian, Jiaqi Shi. The role of KDM6A in pancreatic cancer immune microenvironment [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-125.
Pseudoxanthoma Elasticum With Cutis Laxa-Like Features
Authors: Meredith Gaufin, Michael A. Cardis
Journal: JAMA Dermatology (2021)

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Rates and Predictors of Visits to Primary Care Physicians during and after Treatment of Childhood Acute Lymphoblastic Leukemia: A Population-Based Cohort Study
Authors: Vicky R. Breakey, Paul Nathan, Serina Patel, Laura Wheaton, Qing Li, Rinku Sutradhar, Mylene Bassal, Paul J. Gibson, Jason Pole, Uma H. Athale, Sumit Gupta
Journal: Blood (2021)
Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia: Why Do Adolescents and Young Adults Outcomes Differ from Those of Children? a Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)
Authors: Audrey Grain, Fanny Rialland, Patrice Chevallier, Nicolas Blin, Jean-Hugues Dalle, Gerard Michel, Nathalie Dhedin, Regis Peffault De Latour, Cecile Pochon, Ibrahim yakoub Agha, Yves Bertrand, Anne Sirvent, Charlotte Jubert, Edouard Forcade, Anna Berceanu, Virginie Gandemer, Pascale Schneider, Jacques-Olivier Bay, Pierre Simon Rohrlich, Eolia Brissot, Catherine Paillard, Dominique Plantaz, Stephanie Nguyen Quoc, Fanny Gonzales, Natacha Maillard, Lucie Planche, Andre Baruchel
Journal: Blood (2021)
The impact of public–private partnerships for roadway projects on traffic safety: An exploratory empirical analysis of crash frequencies
Authors: Sarvani Sonduru Pantangi, Grigorios Fountas, Md Tawfiq Sarwar, Abhishek Bhargava, Satish B. Mohan, Peter Savolainen, Panagiotis Ch. Anastasopoulos
Journal: Analytic Methods in Accident Research (2021)
Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression
Authors: Cuiqin Fan, Ye Li, Tian Lan, Wenjing Wang, Yifei Long, Shu Yan Yu
Journal: Molecular Therapy (2021)

Enhancing neurogenesis within the hippocampal dentate gyrus (DG) is critical for maintaining brain development and function in many neurological diseases. However, the neural mechanisms underlying neurogenesis in depression remain unclear. Here, we show that microglia transfer a microglia-enriched microRNA, miR-146a-5p, via secreting exosomes to inhibit neurogenesis in depression. Overexpression of miR-146a-5p in hippocampal DG suppresses neurogenesis and spontaneous discharge of excitatory neurons by directly targeting Krüppel-like factor 4 (KLF4). Downregulation of miR-146a-5p expression ameliorates adult neurogenesis deficits in DG regions and depression-like behaviors in rats. Intriguingly, circular RNA ANKS1B acts as a miRNA sequester for miR-146a-5p to mediate post-transcriptional regulation of KLF4 expression. Collectively, these results indicate that miR-146a-5p can function as a critical factor regulating neurogenesis under conditions of pathological processes resulting from depression and suggest that microglial exosomes generate new crosstalk channels between glial cells and neurons.
14q32 MicroRNA Inhibition Reduces Atherosclerotic Lesion Formation, Increases Plaque Stability and Lowers Cholesterol Levels
Authors: A. Wezel, S. Welten, W. Razawy, M. Lagraauw, de Vries, , M., E. Kandimalla, J. Kuiper, P. Quax, I. Bot, Y. Nossent
Journal: Circulation (2013)
A Novel Machine Learning-Derived Molecular Classification Scheme with Prognostic Significance
Authors: Tariq Kewan, Arda Durmaz, Hassan Awada, Carmelo Gurnari, Waled Bahaj, Simona Pagliuca, Laila Terkawi, Ramsha Ahmed, Suresh Kumar Balasubramanian, Bhumika J. Patel, Hetty E. Carraway, Valeria Visconte, Torsten Haferlach, Jaroslaw P. Maciejewski
Journal: Blood (2021)
Abstract 9070: Use of Commercial Outpatient Monitoring for Near-Real-Time, Acute- and Subacute-Care Telemetry Like Monitoring in Covid-19 Pandemic
Authors: Jian Tan, Jonathan Krathen, Krystal Hunter, John A Andriulli, Matthew Ortman, Andrea M Russo
Journal: Circulation (2021)

Introduction: Limited data exist on the role of commercial mobile cardiac telemetry (MCT) monitoring with QT capability as a near-real-time inpatient monitoring tool for COVID-19 stable patients. Our aim was to determine whether outpatient MCT monitoring could be adapted for near-real-time inpatient arrhythmia and QT monitoring during the COVID-19 pandemic. Methods: We conducted a prospective observational study on patients ≥18 years old with confirmed COVID-19 who required hospitalization between June and December 2020. Data including baseline characteristics and laboratory data were collected. Cardiac rhythms monitored using the MCT monitors (Medilynx Pocket ECG) were analyzed (beat-to-beat analysis). Off-site technicians monitored for arrhythmias 24/7 and notified the physician based on the pre-defined events (QTc ≥500 ms with QRS &lt;120 ms or QTc &gt;520 ms with QRS ≥120 ms or atrial and/or ventricular tachyarrhythmia ≥5 beats). Primary endpoint was the detection of any of the pre-defined events. Results: 29 patients were enrolled in this study. 65.5% were female. There were no significant differences except age in baseline characteristics and laboratory data between those with and without events. Patient age was a significant predictor of events at multivariable analysis [odds ratio 1.08, 95% CI (1.01 - 1.15); P = 0.023]. Table 1 showed the overall number and events recorded on the MCT monitors. Two patients had new-onset atrial fibrillation (AF) and 5 patients had AF with heart rate &gt;100 bpm. In retrospective analysis, these findings correlated with the 12-lead ECGs performed during their hospital stays. Two patient had significant QTc prolongation noted on the MCT monitor. No adverse events occurred in any of the monitored patients. Conclusions: Our results showed that commercial MCT monitoring can potentially provide a system for detecting clinically relevant arrhythmias and QT prolongation, especially if there is a subsequent shortage of telemetry monitors.
Second Line Treatment Strategies in Multiple Myeloma: A Referral-Center Experience
Authors: Sarah Goldman-Mazur, Alissa Visram, S Vincent Rajkumar, Prashant Kapoor, Angela Dispenzieri, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, Suzanne R. Hayman, David Dingli, Taxiarchis Kourelis, Wilson I Gonsalves, Rahma M Warsame, Eli Muchtar, Nelson Leung, Robert A. Kyle, Shaji Kumar
Journal: Blood (2021)
A multifunctional nanotheranostic agent potentiates erlotinib to EGFR wild-type non-small cell lung cancer
Authors: Duo Wang, Jun Zhou, Weimin Fang, Cuiqing Huang, Zerong Chen, Meng Fan, Ming-Rong Zhang, Zeyu Xiao, Kuan Hu, Liangping Luo
Journal: Bioactive Materials (2021)

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as Erlotinib, have demonstrated remarkable efficacy in the treatment of non-small cell lung cancer (NSCLC) patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type (wt) EGFR tumours has been shown to be marginal. Methods that can sensitize Erlotinib to EGFR wild-type NSCLC remain rare. Herein, we developed a multifunctional superparamagnetic nanotheranostic agent as a novel strategy to potentiate Erlotinib to EGFR-wt NSCLCs. Our results demonstrate that the nanoparticles can co-escort Erlotinib and a vascular epithermal growth factor (VEGF) inhibitor, Bevacizumab (Bev), to EGFR-wt tumours. The nanotheranostic agent exhibits remarkable effects as an inhibitor of EGFR-wt tumour growth. Moreover, Bev normalizes the tumour embedded vessels, further promoting the therapeutic efficacy of Erlotinib. In addition, the tumour engagement of the nanoparticles and the vascular normalization could be tracked by magnetic resonance imaging (MRI). Collectively, our study, for the first time, demonstrated that elaborated nanoparticles could be employed as a robust tool to potentiate Erlotinib to EGFR-wt NSCLC, paving the way for imaging-guided nanotheranostics for refractory NSCLCs expressing EGFR wild-type genes.
Quality measures in HCC care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases
Authors: Sumeet K. Asrani, Marwan S. Ghabril, Alexander Kuo, Raphael B. Merriman, Timothy Morgan, Neehar D. Parikh, Nadia Ovchinsky, Fasiha Kanwal, Michael L. Volk, Chanda Ho, Marina Serper, Shivang Mehta, Vatche Agopian, Roniel Cabrera, Victoria Chernyak, Hashem B. El‐Serag, Julie Heimbach, George N. Ioannou, David Kaplan, Jorge Marrero, Neil Mehta, Amit Singal, Riad Salem, Tamar Taddei, Anne M. Walling, Elliot B. Tapper
Journal: Hepatology (2021)

Abstract The burden of HCC is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process‐based measures and patient‐reported outcomes (PROs) along the HCC care continuum. We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13‐member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate PROs based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha‐fetoprotein [AFP]) every 6 months, need for surveillance in high‐risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging‐Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high‐risk population.
Second <i>Versus</i> First Wave of COVID-19 in Patients with MPN
Authors: Tiziano Barbui, Alessandra Iurlo, Arianna Masciulli, Alessandra Carobbio, Arianna Ghirardi, Greta Carioli, Marta Sobas, Elena Maria Elli, Elisa Rumi, Valerio De Stefano, Francesca Lunghi, Monia Marchetti, Rosa Daffini, Mercedes Gasior Kabat, Beatriz Cuevas, Laura Maria Fox, Marcio Andrade, Francesca Palandri, Paola Guglielmelli, Giulia Benevolo, Claire N. Harrison, Maria Angeles Foncillas, Massimiliano Bonifacio, Alberto Alvarez-Larran, Jean-Jacques Kiladjian, Estefanía Bolaños, Andrea Patriarca, Keina Quiroz, Martin Griesshammer, Valentín Garcia Gutierrez, Alberto Marin Sanchez, Elena Magro, Marco Ruggeri, Juan Carlos Hernandez Boluda, Santiago Osorio, Gonzalo Carreño Gomez-Tarragona, Miguel Sagüés, Rajko Kusec, Begoña Navas, Anna Angona, Blanca Xicoy, Emma Lopez Abadia, Steffen Koschmieder, Daniele Cattaneo, Cristina Bucelli, Edyta Cichocka, Anna Masternak, Fabrizio Cavalca, Oscar Borsani, Silvia Betti, Marta Bellini, Natalia Curto-Garcia, Alessandro Rambaldi, Alessandro Vannucchi
Journal: Blood (2021)
Off-the-Shelf, iPSC-Derived CAR-NK Cells Multiplexed-Engineered for the Avoidance of Allogeneic Host Immune Cell Rejection
Authors: Rina M Mbofung, Alan M Williams, Ken Hayama, Yijia Pan, Brian Groff, Thomas Dailey, Sonia Reyes, Sajid Mahmood, Ketan Mathavan, Greg Bonello, Quirin Hammer, Karl-Johan Malmberg, Tom Lee, Ryan Bjordahl, Jode P Goodridge, Bahram Valamehr
Journal: Blood (2021)
Venetoclax Plus Decitabine for Young Adults with Newly Diagnosed ELN Adverse-Risk Acute Myeloid Leukemia: Interim Analysis of a Prospective, Multicenter, Single-Arm, Phase 2 Trial
Authors: Suning Chen, Jundan Xie, Xiaofei Yang, Hongjie Shen, Jiannong Cen, Li Yao, Xiaohui Hu, Qian Wu, Jingren Zhang, Hongchun Qiu, Xiaowen Tang, Aining Sun, Shengli Xue, Ying Wang, Huiying Qiu, Depei Wu
Journal: Blood (2021)
Erratum : Obesity is associated with hypothalamic injury in rodents and humans (The Journal of Clinical Investigation (2012) 122, 1, (153-162) DOI: 10.1172/JCI59660)
Authors: Joshua P. Thaler, Chun Xia Yi, Ellen A. Schur, Stephan J. Guyenet, Bang H. Hwang, Marcelo O. Dietrich, Xiaolin Zhao, David A. Sarruf, Vitaly Izgur, Kenneth R. Maravilla, Hong T. Nguyen, Jonathan D. Fischer, Miles E. Matsen, Brent E. Wisse, Gregory J. Morton, Tamas L. Horvath, Denis G. Baskin, Matthias H. Tschöp, Michael W. Schwartz
Journal: Journal of Clinical Investigation (2012)
The REPAIR Study
Authors: Anton Vonk Noordegraaf, Richard Channick, Emmanuelle Cottreel, David G. Kiely, J. Tim Marcus, Nicolas Martin, Olga Moiseeva, Andrew Peacock, Andrew J. Swift, Ahmed Tawakol, Adam Torbicki, Stephan Rosenkranz, Nazzareno Galiè
Journal: JACC. Cardiovascular imaging (2021)

The REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study evaluated the effect of macitentan on right ventricular (RV) and hemodynamic outcomes in patients with pulmonary arterial hypertension (PAH), using cardiac magnetic resonance (CMR) and right heart catheterization (RHC). RV failure is the primary cause of death in PAH. CMR is regarded as the most accurate noninvasive method for assessing RV function and remodeling and CMR measures of RV function and structure are strongly prognostic for survival in patients with PAH. Despite this, CMR is not routinely used in PAH clinical trials. REPAIR was a 52-week, open-label, single-arm, multicenter, phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition, on RV remodeling and function and cardiopulmonary hemodynamics. Primary endpoints were change from baseline to week 26 in RV stroke volume, determined by CMR; and pulmonary vascular resistance, determined by RHC. Efficacy measures were assessed for all patients with baseline and week 26 data for both primary endpoints. At a prespecified interim analysis in 42 patients, both primary endpoints were met, enrollment was stopped, and the study was declared positive. At final analysis (n = 71), RV stroke volume increased by 12 mL (96% confidence level: 8.4-15.6 mL; P < 0.0001) and pulmonary vascular resistance decreased by 38% (99% confidence level: 31%-44%; P < 0.0001) at week 26. Significant positive changes were also observed in secondary and exploratory CMR (RV and left ventricular), hemodynamic, and functional endpoints at week 26. Improvements in CMR RV and left ventricular variables and functional parameters were maintained at week 52. Safety (n = 87) was consistent with previous clinical trials. In the context of this study, macitentan treatment in patients with PAH resulted in significant and clinically-relevant improvements in RV function and structure and cardiopulmonary hemodynamics. At 52 weeks, improvements in RV function and structure were sustained. (REPAIR: Right vEntricular remodeling in Pulmonary ArterIal hypeRtension [REPAIR]; NCT02310672)
Patients are at risk as NHS reaches unsafe “tipping point,” leaders warn government
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The NHS is now under unsustainable levels of pressure, with patients’ safety and care at risk from chronic staff shortages, healthcare leaders have warned.

A new poll of over 450 NHS leaders in England by the NHS Confederation paints a bleak picture of a service in crisis, with primary care and urgent and emergency care the greatest areas of concern.1

Official NHS figures released on 11 November show that major emergency departments treated more than 1.4 million people in October, the highest ever for this month and the third highest monthly number of all time, while ambulance staff responded to more than 82 000 …