tbuckley/cabot-search huggingface dataset:
Abstract 9472: Multicenter Comparison of Staged vs. Complete Repair in Young Infants With Tetralogy of Fallot with Pulmonary Atresia and Confluent Branch Pulmonary Arteries
Authors: Katerina Boucek, Christopher Mastropietro, Jonathan Beall, Everette Keller, Asaad Beshish, Saul Flores, Meghan Chlebowski, Andrew R Yates, Tarif Choudhury, Dana Mueller, David M Kwiatkowski, Karl Migally, Karan Karki, Renee Willett, Monique R Radman, Chetana Reddy, Kurt Piggott, Christine Capone, Yamini Kapileshwarkar, Niranjan Vijayakumar, Elizabeth Prentice, Sukumar Suguna Narasimhulu, Renee H Martin, John M Costello
Journal: Circulation (2021)

Introduction: Optimal management of neonates with tetralogy of Fallot and pulmonary atresia (TOF/PA) with confluent pulmonary arteries is unknown. We sought to compare outcomes for patients who underwent primary complete repair vs. initial surgical palliation followed by delayed repair. Methods: We conducted a retrospective study at 20 centers within CoRe-PCICS (Collaborative Research from the Pediatric Cardiac Intensive Care Society). Data were collected on infants undergoing initial surgical intervention at 0 - 60 days of age with TOF/PA from 2009 to 2018, excluding patients with MAPCAs or those undergoing ductal stenting (n=22). The primary outcome was days alive and out of hospital in first year of life (DAOH). Secondary outcomes were 1 year mortality and a composite major complication outcome (similar to that in prior STS-CHSD studies), defined as occurrence of ≥ 1 of the following: renal failure requiring dialysis, stroke/seizure, permanent pacemaker, ECMO, or diaphragm paralysis during a palliation and/or repair hospitalization, or unplanned reoperation in the first year. Multivariable modeling with generalized estimating equations were utilized to compare outcomes between groups. Results: Of 210 subjects, 79 underwent primary complete repair and 131 underwent surgical palliation. Patients who underwent palliation had greater use of preoperative mechanical ventilation at first procedure (26% vs. 8%, p = 0.002). Other baseline characteristics were similar between groups (p &gt; 0.05 for all). There was no statistically significant difference in DAOH between the palliation and primary repair groups [median (25%,75% IQR): 319 (280,336) vs. 338 (314,348 days), adjusted p = 0.20]. Nine (7%) patients who underwent palliation died in the first year of life vs. 4 (6 %) who underwent primary repair (adjusted OR: 1.1, 95% CI: 0.3-4.5; p = 0.9). At least one major complication occurred in 35% of patients who underwent palliation vs. 18% of patients who underwent primary repair (adjusted OR: 2.5, 95% CI: 1.4-4.4, p = 0.001). Conclusions: For infants with TOF/PA with confluent pulmonary arteries, a strategy of surgical palliation or primary complete repair resulted in similar DAOH and early mortality, whereas the morbidity incidence favored primary repair.
PATH-28. RE-DEFINING CLONALITY OF THE TERT PROMOTER MUTATION WITH DEEP SEQUENCING AND MAXIMAL SAMPLING OF NEWLY DIAGNOSED AND RECURRENT GBM AND OLIGODENDROGLIOMA
Authors: Christina Appin, Abigail K Suwala, Stephanie Hilz, Radhika Mathur, Ivan Smirnov, Chibo Hong, Nicholas Stevers, Anny Shai, Mitchel Berger, Susan Chang, Joanna Phillips, Joseph Costello
Journal: Neuro-Oncology (2021)

Abstract TERT promoter mutation (TPM), found in over 80% of IDH-wildtype glioblastomas (GBMs) and oligodendrogliomas, leads to reactivation of telomerase and consequently tumor cell immortalization, which is potentially reversible. TERT could therefore serve as an effective target in treating tumors with TPM, if TPM is present throughout the tumor. Previous studies using a single sample or minimal sampling per tumor have shown potentially conflicting results, suggesting TPM is clonal in some cases and subclonal in others. Here we use spatially mapped tumor samples representing maximal tumor sampling to address this critical issue. Sanger sequencing was performed on 311 newly diagnosed and recurrent tumor samples from 19 IDH-wildtype GBMs and 10 oligodendrogliomas. To validate Sanger sequencing and resolve potentially ambiguous samples, deep amplicon sequencing was performed on 164 samples. To determine tumor purity and TERT expression levels, whole exome sequencing (164 samples) and RNA-Seq (129 samples) data sets were analyzed computationally. Sanger and amplicon sequencing showed that TPM was present in 305 of 311 samples (98.1%). TPM was not detected in 6 samples which had tumor purity estimates too low to be accurately determined by FACETS and lacked evidence of any driver mutation. Variant allele frequencies (VAFs) of TPM showed high positive correlation with those of clonal alterations in GBMs (r(90) = .93, p &amp;lt; .0001) and oligodendrogliomas (r(48) = .96, p &amp;lt; .0001). TPM VAFs also showed high positive correlation with tumor purity in both GBMs (r(112) = .92, p &amp;lt; .0001) and oligodendrogliomas (r(48) = .89, p &amp;lt; .0001). TPM VAF showed a moderate positive correlation with TERT expression in GBMs (r(78) = .40, p &amp;lt; .001) and oligodendrogliomas (r(47) = .49, p &amp;lt; .001). Therefore, TPM is a tumor-wide, clonal mutation in both newly diagnosed and recurrent GBMs and oligodendrogliomas. TPM VAF is moderately correlated with TERT expression.
High-resolution ex vivo analysis of the degradation and osseointegration of Mg-xGd implant screws in 3D
Authors: Diana Krüger, Silvia Galli, Berit Zeller-Plumhoff, D.C. Florian Wieland, Niccolò Peruzzi, Björn Wiese, Philipp Heuser, Julian Moosmann, Ann Wennerberg, Regine Willumeit-Römer
Journal: Bioactive Materials (2021)

Biodegradable magnesium (Mg) alloys can revolutionize osteosynthesis, because they have mechanical properties similar to those of the bone, and degrade over time, avoiding the need of removal surgery. However, they are not yet routinely applied because their degradation behavior is not fully understood. In this study we have investigated and quantified the degradation and osseointegration behavior of two biodegradable Mg alloys based on gadolinium (Gd) at high resolution. Mg-5Gd and Mg-10Gd screws were inserted in rat tibia for 4, 8 and 12 weeks. Afterward, the degradation rate and degradation homogeneity, as well as bone-to-implant interface, were studied with synchrotron radiation micro computed tomography and histology. Titanium (Ti) and polyether ether ketone (PEEK) were used as controls material to evaluate osseointegration. Our results showed that Mg-5Gd degraded faster and less homogeneously than Mg-10Gd. Both alloys gradually form a stable degradation layer at the interface and were surrounded by new bone tissue. The results were correlated to in vitro data obtained from the same material and shape. The average bone-to-implant contact of the Mg-xGd implants was comparable to that of Ti and higher than for PEEK. The results suggest that both Mg-xGd alloys are suitable as materials for bone implants.
MEK Inhibition Demonstrates Activity in Relapsed, Refractory Patients with Juvenile Myelomonocytic Leukemia: Results from COG Study ADVL1521
Authors: Elliot Stieglitz, Mignon L. Loh, Julia Meyer, Chujing Zhang, Donald A Barkauskas, David Hall, Elizabeth Fox, Brenda J. Weigel
Journal: Blood (2021)
Aberrant CDK7 Activity Drives the Cell Cycle and Transcriptional Dysregulation to Support Multiple Myeloma Growth: An Attractive Molecular Vulnerability
Authors: Yao Yao, Woojun D Park, Eugenio Morelli, Mehmet K. Samur, Nicholas P Kwiatkowski, Ryosuke Shirasaki, Yan Xu, Chandraditya Chakraborty, Behnam Nabet, Marta Chesi, Nathaniel Gray, Richard A. Young, Kenneth C. Anderson, Constantine S. Mitsiades, Lin Charles, Nikhil C. Munshi, Mariateresa Fulciniti
Journal: Blood (2021)
Abstract 9917: Stroke Survivors with Asthma Have Worse Cardiovascular Outcomes
Authors: Stavros Zinonos, Deep Vakil, Wenting Wang, William J Kostis, Javier Cabrera, John B Kostis
Journal: Circulation (2021)

Introduction: Studies have shown that asthmatics have higher risk for cardiovascular (CV) disease and all-cause mortality than non-asthmatics. However, only a few studies have examined the role asthma has on CV outcomes of stroke survivors. Hypothesis: Stroke survivors with asthma have higher risk of CV outcomes (1- and 5-year all-cause mortality, 1- and 5-year admission for stroke recurrence, first occurrence of MI, or HF) than matched stroke survivors without asthma. Methods: A total of 271,260 patients, 18-years-old and older, with index stroke and without a history of HF, MI, or COPD from January 1, 1995 to December 31, 2015 were identified in the Myocardial Infarction Data Acquisition System, a database of all admissions to non-federal hospitals in New Jersey. A matched analysis was performed by separating the cohort into asthmatics (n=11,702) and non-asthmatics (n=34,950) and matched 1 asthmatic up to 3 non-asthmatics. Data was analyzed by matching patient and clinical characteristics. The association of asthma with each of the above outcomes was assessed using logistic regression, log-rank test, and Cox models. Results: There was no difference in 1-and 5-year all-cause mortality (p=0.102 and p=0.488, respectively). Patients with asthma were more likely to be readmitted for stroke within 1 year (hazard ratio (HR)= 1.08, 95% CI 1.00-1.16, p=0.041) and had first admission for HF at 1 year (HR 1.38, 95% CI 1.09-1.73, p=0.006) compared to matched controls. Also, they were more likely to be readmitted for stroke within 5 years (HR 1.08, 95% CI 1.02-1.15, p=0.007) and to be admitted for first HF within 5 years (HR 1.27, 95% CI 1.12-1.44, p&lt;0.001) (Figure). There were no significant differences in 1-year and 5-year first MI admissions. Conclusion: Stroke survivors with asthma have higher risk for stroke readmission and first HF admission compared to matched controls. Randomized studies are needed to confirm these findings and stimulate focused efforts to mitigate this risk.
Abstract 11132: Impact of Obesity and Underweight Status by Body Mass Index on Mortality Among Hospitalized Patients with Hypertrophic Cardiomyopathy
Authors: Jayakumar Sreenivasan, Amanda Lloji, Risheek Kaul, Mohammad S Khan, Aaqib H Malik, Wilbert S Aronow, Erin D Michos, Srihari S Naidu
Journal: Circulation (2021)

Introduction: Even though obesity is associated with increased phenotypic expression in patients with hypertrophic cardiomyopathy (HCM), the effect of body mass index (BMI) on in-hospital mortality among hospitalized patients with HCM has not been established. Hypothesis: We hypothesized that among hospitalized patients with HCM, obesity and underweight status are associated with increased mortality Methods: We evaluated the National Inpatient Sample database to identify all adults (age ≥18 years) with HCM hospitalized for any cardiac illness between 2008 and 2017. Using ICD codes for BMI, the study cohort was stratified into underweight (BMI ≤19.9 kg/m 2 ), non-obese (BMI 20.0-29.9 kg/m 2 ), class I obesity (BMI 30.0-34.9 kg/m 2 ), class II obesity (BMI 35.0-39.9 kg/m 2 ) and class III (BMI ≥40.0 kg/m 2 ). Multiple logistic regression analysis was used to analyze the independent association of various BMI categories and in-hospital mortality adjusted for age, sex and medical comorbidities. Results: The survey-weighted sample included a total of 2,392,325 hospitalizations with a mean age of 66.1±12.2 years and 42.0% were females. The patients with class III obesity [adjusted mortality rate (AMR) 3.3%, adjusted odds ratio (AOR) 1.53, 95% confidence interval (CI)-1.29-1.82, p &lt;0.001] and underweight patients (AMR 4.4%, AOR 2.07, 95% CI-1.74-2.46, p &lt;0.001) had higher in-hospital mortality whereas patients with class I obesity (AMR-0.8%, AOR 0.35, 95% CI-0.27-0.45, p &lt;0.001) and patients with class II obesity (AMR-0.8%, AOR 0.34, 95% CI-0.26-0.45, p &lt;0.001) had lower mortality compared to non-obese patients (AMR-2.2%) Conclusions: Among patients with HCM, BMI has a non-linear U-shaped relationship with in-hospital mortality. The patients who were underweight and morbidly obese had significantly higher mortality, whereas those patients with class I and class II obesity had lower mortality compared to non-obese patients.
Abstract 14253: Combining History Of Present Illness With Risk Stratification Scores To Predict Intensive Care Admission For Suspicious Acute Coronary Syndrome Patients In The Emergency Department
Authors: Diyang Xue, Stephanie O Frisch, Adam N Frisch, Zhendong Wang, Zhimeng Luo, He Daqing
Journal: Circulation (2021)

Introduction: Patient symptom data are recorded in free text notes in the electronic health records and are difficult to extract. Natural language processing (NLP) is a technique that can be used to mine key patient symptoms that can be combined with risk stratification tools to improve patient outcomes. Hypothesis: Adding symptom data to the National Early Warning Score (NEWS) and quick sequential organ failure assessment score (qSOFA) will improve the area under the receiver operating curve (AUC) performance. Methods: NEWS scores and qSOFA scores were calculated with assistance from an emergency medicine physician for each patient with suspicion of acute coronary syndrome at initial emergency department (ED) assessment. Independent reviewers annotated the outcome of admission to the intensive care unit as a binary outcome (yes/no). The Apache clinical Text Analysis Knowledge Extraction System (cTAKES), an open access NLP platform, was used to preprocess and run analysis on patient free text ED history of present illness notes. Patient symptom data were extracted and used as patient features/input variables and combined with variables from the NEWS and qSOFA scores. Logistic regression model was used to do prediction. We used DeLong’s test to determine the statistical difference between each scores’ AUC. Results: 70 patients out of 1195 had an intensive care admission. The AUC for the NEWS and qSOFA scores were 0.75 and 0.67, respectively. After adding symptoms features, the AUCs improved to 0.81 and 0.79, respectively. There were statistical differences between the AUCs between each score. Conclusion: Adding patient symptom data improves performance of both the NEWS and qSOFA risk stratification scores. Enhanced risk stratification scores with symptom data could identify those at high risk for clinical deterioration and could help augment accurate decision making at ED disposition.
Isocitrate Dehydrogenase (IDH) 1 and 2 Mutation Is an Independent Predictor of Better Outcome in Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Study of the ALWP of EBMT
Authors: Razan Mohty, Abdul Hamid Bazarbachi, Myriam Labopin, Jordi Esteve, Nicolaus Kröger, Jan J. Cornelissen, Didier Blaise, Gerard Socie, Sébastien Maury, Arnold Ganser, Jean-Henri Bourhis, Claude-Eric Bulabois, Ibrahim Yakoub-Agha, Stephanie Nguyen, Patrice Chevallier, Ali Bazarbachi, Arnon Nagler, Mohamad Mohty
Journal: Blood (2021)
Novel Evidence That Alternative Activation Pathway of Complement Cascade (ComC) Regulates Optimal Homing and Engraftment of Hematopoietic Stem/Progenitor Cells (HSPCs) in Reactive Oxygen Species (ROS) - Nlrp3 Inflammasome-Dependent Manner
Authors: Mateusz Adamiak, Andrzej Ciechanowicz, Kamila Bujko, Katarzyna Brzeźniakiewicz-Janus, Janina Ratajczak, Magda Kucia, Mariusz Z Ratajczak
Journal: Blood (2021)
Pretreatment in the Setting of Non–ST-Elevated Acute Coronary Syndrome—When It Is Time to Change
Authors: Michel Zeitouni, Jean-Philippe Collet
Journal: JAMA Network Open (2021)

Luke P. Dawson, MBBS, MPH; David Chen; Misha Dagan, MMed(ClinEpi), MD; Jason Bloom, MBBS; Andrew Taylor, MBBS, PhD; Stephen J. Duffy, MBBS, PhD; James Shaw, MBBS, PhD; Jeffrey Lefkovits, MBBS; Dion Stub, MBBS, PhD
Abstract 9516: Comparison of Mortality Rates Among Rate Control Agents in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Angkawipa Trongtorsak, Jakrin Kewcharoen, Sakditad Saowapa, Natchaya Polpichai, Sittinun Thangjui, Leenhapong Navaravong
Journal: Circulation (2021)

Introduction: Rate control strategy is an effective treatment strategy for patients with atrial fibrillation (AF). However, data supporting the selection of rate-control medications is still lacking. We conducted a systematic review and meta-analysis to evaluate and compare mortality rate among beta-blocker (BB), calcium channel blocker (CCB), and digoxin for patients with AF undergoing rate control strategy. Methods: We searched MEDLINE, and EMBASE databases from inception to May 2021 to identify studies that compared all-cause mortality among patients who received single rate-control medication (BB, CCB, or digoxin). Data from each study were combined using the random-effects model to calculate pooled relative risk (RR) with 95% confidence interval (CI). Results: Five studies (2 randomized control trial and 3 retrospective cohort studies) with a total of 105,129 patients (45,910, 19,241, and 39,978 patients were in BB, CCB, and digoxin groups respectively) were included. Patients in digoxin group had higher mortality rates when compared to the BB group (pooled RR=0.55, 95%CI 0.5-0.61, p=&lt;0.001) and the CCB group (pooled RR=0.73, 95%CI 0.56-0.95, p=0.018). There was a trend favoring BB when comparing BB to CCB, but failed to reach statistical significance (pooled RR=0.76, 95%CI 0.57-1, p=0.052). Conclusions: Our meta-analysis showed that rate control strategy in AF patients with digoxin was associated with higher mortality rates, but there was no statistical difference of the survival outcome between BB and CCB.
Propensity Score Matching Analysis Comparing Ruxolitinib Vs Historical Controls in 2 nd Line or Beyond Treatment for Chronic Gvhd after Therapy Failure
Authors: Igor Novitzky-Basso, Swe Mar Linn, Jennifer White, Mohamed Elemary, Anargyros Xenocostas, Nada Hamad, Sui Tan, Samantha Culos, Arjun Law, Dennis Dong Hwan Kim
Journal: Blood (2021)
Metabolically Reprogrammed Polyclonal Autologous Rapa-201 Cell Therapy Yields a Promising Safety and Efficacy Profile in Relapsed and Refractory Multiple Myeloma (RRMM)
Authors: Binod Dhakal, Tania Felizardo, Lawrence G. Lum, Anita D'Souza, Saurabh Chhabra, Taylor Keaton, Meera Mohan, Jee H Park, Daniel H Fowler, Parameswaran Hari
Journal: Blood (2021)
Metformin for Treatment of Cytopenias in Children and Young Adults with Fanconi Anemia
Authors: Jessica A. Pollard, Elissa M. Furutani, Shanshan Liu, Erica B. Esrick, Laurie Cohen, Jacob Bledsoe, Kun Lu, Maria Jose Ramirez, Jordi Surrallés, Maggie Malsch, Ashley Kuniholm, Ashley Galvin, Myriam Armant, Annette S. Kim, Kaitlyn Ballotti, Lisa Moreau, Yu Zhou, Daria V. Babushok, Farid Boulad, Clinton Carroll, Helge Hartung, Amy Hont, Taizo A. Nakano, Timothy S. Olson, Sei-Gyung K. Sze, Alexis A Thompson, Marcin W. Wlodarski, Towia A Libermann, Alan D. D'Andrea, Markus Grompe, Edie A. Weller, Akiko Shimamura
Journal: Blood (2021)
Feasibility of Using Real-world Data to Emulate Postapproval Confirmatory Clinical Trials of Therapeutic Agents Granted US Food and Drug Administration Accelerated Approval
Authors: Joshua D. Wallach, Audrey D. Zhang, Joshua J. Skydel, Victoria L. Bartlett, Sanket S. Dhruva, Nilay D. Shah, Joseph S. Ross
Journal: JAMA Network Open (2021)

Joshua D. Wallach, PhD, MS; Reshma Ramachandran, MD, MPP; Till Bruckner, PhD; Joseph S. Ross, MD, MHS
Ibrutinib Treatment in CLL Interrupts CD40 Signaling Capacity and Sensitizes CLL Cells to Venetoclax
Authors: Karoline Kielbassa, Marco Haselager, Danique Bax, Julie Dubois, Mark-David Levin, Peter E. Westerweel, Rebecka Svanberg, Carsten Utoft Niemann, Arnon P. Kater, Eric Eldering
Journal: Blood (2021)
Update of Multicenter, Retrospective Evaluation of Overall Response and Failure Free Survival Following Ruxolitinib Therapy for Heavily Pre-Treated Chronic Gvhd Patients with Steroid-Failure: A Proposal of Risk Score Model for Failure-Free Survival
Authors: Jennifer White, Mohamed Elemary, Swe Mar Linn, Igor Novitzky-Basso, Anargyros Xenocostas, Nada Hamad, Samantha Culos, Sui Tan, Arjun Law, Rajat Kumar, Jonas Mattsson, Dennis Dong Hwan Kim
Journal: Blood (2021)
Phase 1/2 Study of Nexi-002 Autologous Multi-Antigen-Specific CD8+ T Cells for the Treatment of Relapsed or Refractory Multiple Myeloma
Authors: Robert D Knight, Myo Htut, Juan C. Varela, Andrew Kin, Vineetha Edavana, Emily Lu, Sojung Kim, Lauren Suarez, Mathias Oelke, Daniel Bednarik
Journal: Blood (2021)
Molecular and clinical characterization of transient antithrombin deficiency: A new concept in congenital thrombophilia
Authors: Carlos Bravo‐Pérez, María Eugenia de la Morena‐Barrio, Belén de la Morena‐Barrio, Antonia Miñano, José Padilla, Rosa Cifuentes, Pedro Garrido, Vicente Vicente, Javier Corral
Journal: American Journal of Hematology (2021)

Abstract Antithrombin deficiency, the most severe thrombophilia, might be underestimated, since it is only investigated in cases with consistent functional deficiency or family history. We have analyzed 444 consecutive, unrelated cases, from 1998 to 2021, with functional results supporting antithrombin deficiency in at least one sample. Plasma antithrombin was evaluated by functional and biochemical methods in at least two samples. SERPINC1 gene was analyzed by sequencing and MPLA. Hypoglycosylation was studied by electrophoresis and high‐performance liquid chromatography (HPLC). In 260 of 305 cases (85.2%) with constitutive deficiency (activity &lt; 80% in all samples), a SERPINC1 ( N = 250), or N‐glycosylation defect ( N = 10) was observed, while 45 remained undetermined. The other 139 cases had normal antithrombin activity (≥ 80%) in at least one sample, what we called transient deficiency. Sixty‐one of these cases (43.9%) had molecular defects: 48 had SERPINC1 variants, with two recurrent mutations (p.Ala416Ser[Cambridge II], N = 15; p.Val30Glu[Dublin], N = 12), and 13 hypoglycosylation. Thrombotic complications occurred in transient deficiency, but were less frequent, latter‐onset, and had a higher proportion of arterial events than in constitutive deficiency. Two mechanisms explained transient deficiency: The limitation of functional methods to detect some variants and the influence of external factors on the pathogenic consequences of these mutations. Our study reveals a molecular defect in a significant proportion of cases with transient antithrombin deficiency, and changes the paradigm of thrombophilia, as the pathogenic effect of some mutations might depend on external factors and be present only at certain timepoints. Antithrombin deficiency is underestimated, and molecular screening might be appropriate in cases with fluctuating laboratory findings.
Vaccination Status and the Detection of SARS-CoV-2 Infection in Health Care Personnel Under Surveillance in Long-term Residential Facilities
Authors: Katherine Linsenmeyer, Michael E. Charness, William J. O’Brien, Judith Strymish, Sucheta J. Doshi, Sven K. Ljaamo, Kalpana Gupta
Journal: JAMA Network Open (2021)
The Prognosis of Intermediate- and High-Risk Young AML Patients Who Did Not Receive Allo-HSCT Treated with Intensive Chemotherapy Is Not Superior to That of Elderly AML Patients Treated with the D-CAG Regimen
Authors: Ming Hong, Qian Sun, Wenjie Liu, Han Zhu, Yu Zhu, Jianyong Li, Sixuan Qian
Journal: Blood (2021)
Being Present-CML: A Distress Reduction Intervention for Patients with Chronic Myeloid Leukemia Taking Tyrosine Kinase Inhibitors
Authors: Kelly L. Schoenbeck, Anand Dhruva, Albert Lee, Neha G. Goyal, Adrienne K. Yang, Sa Ra Park, Catherine C. Smith, Neil P Shah, Chloe E. Atreya
Journal: Blood (2021)