tbuckley/cabot-search huggingface dataset:
Abstract 13173: Early Determination of Residual Inflammatory Risk and Its Association With Adverse Clinical Events in East Asian Patients Treated With Percutaneous Coronary Intervention
Authors: Jong-Hwa Ahn, Tantry Udaya, Min Gyu Kang, Hyun Woong Park, Jin-sin Koh, Jae Seok Bae, Sang Young Cho, Kye-Hwan Kim, Jeong Yoon Jang, Jeong Rang Park, Yongwhi Park, Markus Schlaich, Choong Hwan Kwak, Jin-Yong Hwang, Paul A. Gurbel, Young-hoon Jeong
Journal: Circulation (2021)

Background: East Asian population has substantially low level of inflammation compared with Western population. It remains uncertain that early determination of residual inflammatory risk (RIR) and its clinical impact in East Asian patients with coronary artery disease (CAD). Methods: This was a cohort analysis with CAD patients (n=5,840) undergoing percutaneous coronary intervention (PCI) with serial assessment of inflammatory status from East Asian registry. Inflammatory status was determined by measuring high-sensitivity C-reactive protein (hs-CRP) at on-admission and 1-month follow-up. Patients were stratified into 4 groups according to hs-CRP criteria (≥2 mg/L): (1) persistent low RIR (51.0%); (2) fortified RIR (low on-admission -high 1-month ) (10.3%); (3) attenuated RIR (high on-admission -low 1-month ) (12.1%); and (4) persistent high RIR (18.3%). Primary endpoint was defined as a composite of CV death, non-fatal MI, and non-fatal stroke. Results: With a median follow-up of 37.0 (IQR: 19.9, 72.9) months, primary endpoint was occurred in 11.4% of the cohort. Levels of hs-CRP were decreased over time (on-admission vs. 1-month: median 1.3 vs. 0.9 mg/L; P &lt;0.001), which association with primary outcome appeared incremental. Risk of primary endpoint was significantly different across the groups (log-rank test, P &lt;0.001). After adjustment, patients with persistent high RIR showed a higher risk of primary endpoint compared to subjects with persistent low RIR (adjusted HR, 1.41; 95% confidence interval, 1.12 to 1.78; P &lt;0.001). Conclusion: About one-fifth of East Asian patients with CAD have persistent high RIR, which impact on ischemic events appears robust. Unique RIR profile of these patients may explain their better clinical outcomes compared with Western populations.
Dose Modification Dynamics of Ponatinib in Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) from the PACE and Optic Trials
Authors: Elias J. Jabbour, Michael W. Deininger, Elisabetta Abruzzese, Jane F Apperley, Jorge E. Cortes, Charles Chuah, Daniel J. DeAngelo, John F. DiPersio, Andreas Hochhaus, Jeffrey H. Lipton, Franck E. Nicolini, Javier Pinilla Ibarz, Delphine Rea, Gianantonio Rosti, Philippe Rousselot, Michael J. Mauro, Neil P Shah, Moshe Talpaz, Alexander Vorog, Vickie Lu, Hagop Kantarjian
Journal: Blood (2021)
NCOG-14. REAL-WORLD RETROSPECTIVE ANALYSIS OF TUMOR TREATING FIELDS IN THE TREATMENT OF HIGH-GRADE GLIOMA BASED ON CHINESE POPULATION
Authors: Lingchao Chen, Junrui Chen, Kun Song, Jingtao Nie, Dongxiao Zhuang, Yang Wang, Yu Yao, Jinsong Wu, Zhiyong Qin
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVES Tumor Treating Fields (TTFields) has been approved for the treatment of newly diagnosed and relapsed glioblastoma（GBM）in China in 2020. Only few TTFields data in Asia patients were reported. This retrospective analysis is aimed at investigating the efficacy, safety and the potential relationship with biomarkers of TTFields treatment in the real-world clinical practice of the Chinese glioma population. METHODS High-grade glioma patients who were under TTFields treatment from May 2019 to May 2021 in Shanghai Huashan Hospital were analyzed, including baseline data, efficacy data and incidence of adverse events. RESULTS Eighty-two patients (median age 51.0 [26.0 - 47.0] years) with high-grade glioma were enrolled, including 60 newly diagnosed GBM, 16 recurrent GBM, and 6 WHO grade III gliomas. The median time was 9.9 (4.6-15.7) months for follow-ups, median time for TTFields treatment was 4.3(1.1-20.35) months. The median compliance rate was 90% (40%-97%). For newly diagnosed GBM (n=60) and recurrent GBM (n=16), the 6-month PFS rate were 78.4% (95%CI: 63.9-87.6) and 46.7% (95%CI: 21.2- 67.8) respectively. The 10-month OS rate were 86.3% (95%CI: 69.6- 94.2) and 60.0% (95%CI: 12.6- 88.2) respectively. The 6-month PFS rate in the IDHw/TERTm population was 69.9% (95%CI: 45.9-84.9) and 78.3% (95%CI: 46.5-92.5) in the IDHw/TERTw patients with newly diagnosed GBM. 59(72%) patients had skin-related adverse reactions, and majority are grade 1-2 (grade 1-2, 69.5%; grade 3, 2.5%). CONCLUSIONS This is the 1st retrospective analysis done using TTFields in the treatment of high-grade gliomas in the Chinese population with the largest sample size. From our short follow up, TTFields appears good efficacy among GBM patients. The incidence of skin adverse reactions is higher comparable to published data, but mainly consisted of grade1-2. Long-term efficacy data need to be further followed-up.
CHOP but Not Bendamustine Reverses <i>EZH2</i> Y641 Mutation Induced MHC-I/II Loss in Human Lymphoma Models
Authors: Louisa Catharina Adolph, Quentin Fichaux, Carolin Dorothea Strobl, Martina Antoniolli, Verena Passerini, William David Keay, Vindi Jurinovic, Axel Lechner, Daniel J. Hodson, Michael von Bergwelt, Marion Subklewe, Martina Rudelius, Oliver Weigert
Journal: Blood (2021)
Abstract 11548: The Strongest Sex Difference in Myocarditis Prevalence Occured in Young Adult Patients - A Descriptive, Multi-Center Cohort Study in 7,031 Patients Over 22 Years
Authors: Tharusan Thevathasan, Megan A Kenny, Fabian Schreiber, DeLisa Fairweather, Leslie T Cooper, Jana Last, Finn Jasper J Krause, Julia Paul, Wolfgang C Poller, Carsten Skurk, Ulf Landmesser, Felix Balzer, Bettina Heidecker
Journal: Circulation (2021)

Introduction: Studying the clinical nature of myocarditis on a broad scale across age and sex groups is required to investigate risk factors and patterns of disease. This study aimed to examine patient- and hospital-centered characteristics of patients being hospitalized for myocarditis. Hypothesis: Sex differences in myocarditis prevalence are dependent on age. Methods and Results: We included all patients being hospitalized in three tertiary care centers between 1999 and 2021 with a diagnosis of acute or chronic myocarditis. We utilized Chi-square, T-test, Fisher exact or Wilcoxon-Mann-Whitney U tests. 7,031 patients with acute or chronic myocarditis were included in total. 231 (3.3%) were of pre-pubescent age (&lt;13 years if male, &lt;11 years if female), 410 (5.8%) were adolescent patients (&lt;18 years), 2,089 (29.7%) young adults (18-35 years), 2,535 (36.1%) middle-aged adults (35-54 years) and 1,766 (25.1%) patients were over 54 years (post-menopausal age). The diagnosis of myocarditis was confirmed by endomyocardial biopsy in 1,337 patients (19%), while it was based on clinical parameters and/or magnetic resonance imaging in the remaining patients. Adolescent patients had the highest levels of procalcitonin (6.98 ±44.6 μg/l), troponin T (450 ±1,550 ng/l) and creatine kinase (360 ±677U/l), while pre-pubescent patients had the highest levels of anti-streptolysin antibody (320 ±470 kU/l) and NT-proBNP (14,000 ±20,800ng/l) compared to all other age groups. Left-ventricular ejection fraction decreased over age groups from 60 ±4% in adolescent patients to 44.0 ±16% in senior patients. The strongest sex difference in myocarditis frequency was observed in young (608 female vs. 1,481 male; P&lt;0.001) and middle-aged adults (1,025 female vs. 1,510 male; P&lt;0.001) (see Figure 1). Conclusion: Strong sex differences in myocarditis prevalence were particularly observed in young and middle-aged patients. Sex hormones may determine the risk of developing myocarditis.
Pathogenic Mechanisms Underlying Idiopathic Pulmonary Fibrosis
Authors: Benjamin J. Moss, Stefan W. Ryter, Ivan O. Rosas
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

The pathogenesis of idiopathic pulmonary fibrosis (IPF) involves a complex interplay of cell types and signaling pathways. Recurrent alveolar epithelial cell (AEC) injury may occur in the context of predisposing factors (e.g., genetic, environmental, epigenetic, immunologic, and gerontologic), leading to metabolic dysfunction, senescence, aberrant epithelial cell activation, and dysregulated epithelial repair. The dysregulated epithelial cell interacts with mesenchymal, immune, and endothelial cells via multiple signaling mechanisms to trigger fibroblast and myofibroblast activation. Recent single-cell RNA sequencing studies of IPF lungs support the epithelial injury model. These studies have uncovered a novel type of AEC with characteristics of an aberrant basal cell, which may disrupt normal epithelial repair and propagate a profibrotic phenotype. Here, we review the pathogenesis of IPF in the context of novel bioinformatics tools as strategies to discover pathways of disease, cell-specific mechanisms, and cell-cell interactions that propagate the profibrotic niche.
Effectiveness and adverse events of endoscopic clipping versus band ligation for colonic diverticular hemorrhage: a large-scale multicenter cohort study
Authors: Katsumasa Kobayashi, Naoyoshi Nagata, Yohei Furumoto, Atsushi Yamauchi, Atsuo Yamada, Jun Omori, Takashi Ikeya, Taiki Aoyama, Naoyuki Tominaga, Yoshinori Sato, Takaaki Kishino, Naoki Ishii, Tsunaki Sawada, Masaki Murata, Akinari Takao, Kazuhiro Mizukami, Ken Kinjo, Shunji Fujimori, Takahiro Uotani, Minoru Fujita, Hiroki Sato, Sho Suzuki, Toshiaki Narasaka, Junnosuke Hayasaka, Mitsuru Kaise
Journal: Endoscopy (2021)

Abstract Background Prior studies have shown the effectiveness of both endoscopic band ligation (EBL) and clipping for colonic diverticular hemorrhage (CDH) but have been small and conducted at single centers. Therefore, we investigated which was the more effective and safe treatment in a multicenter long-term cohort study. Methods We reviewed data for 1679 patients with CDH who were treated with EBL (n = 638) or clipping (n = 1041) between January 2010 and December 2019 at 49 hospitals across Japan (CODE BLUE-J study). Logistic regression analysis was used to compare outcomes between the two treatments. Results In multivariate analysis, EBL was independently associated with reduced risk of early rebleeding (adjusted odds ratio [OR] 0.46; P &lt; 0.001) and late rebleeding (adjusted OR 0.62; P &lt; 0.001) compared with clipping. These significantly lower rebleeding rates with EBL were evident regardless of active bleeding or early colonoscopy. No significant differences were found between the treatments in the rates of initial hemostasis or mortality. Compared with clipping, EBL independently reduced the risk of needing interventional radiology (adjusted OR 0.37; P = 0.006) and prolonged length of hospital stay (adjusted OR 0.35; P &lt; 0.001), but not need for surgery. Diverticulitis developed in one patient (0.16 %) following EBL and two patients (0.19 %) following clipping. Perforation occurred in two patients (0.31 %) following EBL and none following clipping. Conclusions Analysis of our large endoscopy dataset suggests that EBL is an effective and safe endoscopic therapy for CDH, offering the advantages of lower early and late rebleeding rates, reduced need for interventional radiology, and shorter length of hospital stay.
EPCO-27. SINGLE-CELL ANALYSIS OF ETMR PATIENT SAMPLES LINKS TRANSCRIPTIONAL PHENOTYPES TO GENETIC DRIVER ALTERATIONS AND INFORMS NOVEL THERAPEUTIC STRATEGIES
Authors: Volker Hovestadt, Alexander Beck, Sander Lambo, McKenzie Shaw, Olivia A Hack, Bernhard Englinger, Johannes Gojo, Sibylle Madlener, Sanda Alexandrescu, Stefan Pfister, Marcel Kool, Mariella G Filbin
Journal: Neuro-Oncology (2021)

Abstract Embryonal tumor with multilayered rosettes (ETMR) is a malignant brain tumor that typically occurs in children under the age of three. Most patients die within two years of diagnosis, and more effective, targeted therapies are urgently needed. To better characterize the oncogenic mechanisms of key driver alterations and identify novel therapeutic targets, we studied the cellular heterogeneity of ETMR using single-cell RNA sequencing. Analyses conducted on &amp;gt;3,000 high-quality cells collected from ten primary and relapse specimens revealed a common cellular hierarchy across all tumors: A highly proliferative neural stem cell-like population (SOX2+) gives rise to intermediate progenitors (ASCL1+) and more differentiated neuron-like cells (STMN2/4+). These malignant populations closely match histological patterns of ETMR (i.e. rosettes, neuropil), as observed by immunofluorescence microscopy. Comparison to single-cell datasets from human embryos indicates resemblance to cell populations of the developing brain, but also reveals key ETMR-specific differences, including expression of the chromosome 19 miRNA cluster (C19MC, the presumed genetic driver of most ETMRs), which is restricted to the stem cell-like population. We next investigated if targeting C19MC is a viable strategy to disrupt the cellular hierarchy of ETMR. Silencing with antisense oligonucleotides shows pronounced reduction of cell line growth for a specific subset of the 46 members of C19MC. These miRNAs share seed sequences with evolutionary conserved miRNAs that have been shown to regulate pluripotency and self-renewal of embryonic stem cells. We hypothesize that select C19MC members play similar roles in ETMR and represent bona fide targets for therapeutic targeting using antisense technology.
Abstract 10572: Efficacy and Safety of Protamine After Catheter Ablation of Atrial Fibrillation: Systematic Review and Meta-Analysis
Authors: Kuldeep Shah, Siddharth Shah, Mohit Turagam, Rahul Bhardwaj, Tahmeed Contractor, Ravi Mandapati, Andrea Natale, Dhanunjaya Lakkireddy, Jalaj Garg
Journal: Circulation (2021)

Introduction: Perioperative anticoagulation management with uninterrupted or minimally interrupted anticoagulation during atrial fibrillation (AF) ablation is thought to be critical to minimize thromboembolic complications. Protamine is often administered to neutralize the effects of heparin and expedite vascular hemostasis post-procedure. Hypothesis: To determine the efficacy and safety of protamine to expedite vascular hemostasis and ambulation in patients undergoing AF ablation. Methods: Electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through June 7, 2021, were performed. The primary outcome was time to ambulate (minutes) and hemostasis (minutes). The secondary outcome was any vascular complications or minor hematoma or cerebrovascular accidents. Results: A total of 5 eligible studies consisting of 637 patients (Protamine group: 515 and no protamine group: 497) were included in the meta-analysis. There was a significant reduction in time to ambulation {mean difference (MD): -176.60, 95% CI -266.87 - -86.32; p&lt; 0.01} and in time to hemostasis between the two groups (MD -13.72, 95% CI -22.01 - -5.44, p&lt;0.01) in the protamine group. There were no differences in the rates of vascular complications (RR 0.46 95% CI 0.17-1.24 for any vascular complication; RR 0.43, 95% CI 0.16-1.2 for minor hematoma) or cerebrovascular accidents (RR 0.62, 95% CI 0.08 - 4.98) between the two groups. Conclusions: Protamine administration was associated with reduced time to ambulation (176 minutes reduction) and time to hemostasis (13 minutes reduction) without an increase in any adverse events.
Abstract 14166: Epigenetic Biomarkers Correlate With Post-stroke Long-term Memory Recovery
Authors: Wei Guo, Xing Yin, Jonathan Claypool, Melanie Moody, Jaroslaw Aronowski, Sean Savitz, David McPherson, keith booher, Shaoling Huang
Journal: Circulation (2021)

Introduction: Epigenetic markers including 5-metylcytosine (5mC) can reflect disease severity and treatment effect. Stroke is a multifactorial disease causing aberrant DNA methylation (DNAm) and memory damage. Hypothesis: Models built for 5mC biomarker panel signatures may be useful for quantitative prediction of post-stroke long-term memory recovery in response to treatment. Methods: Stroke was induced with a middle cerebral artery occlusion (MCAO)(18 rats: sham(6), stroke(6), and stroke with treatment (6)). Xe-liposomes were intravenously administrated repetitively for 3 days after MCAO. At day 35, memory was assessed and scaled using a novel objective recognition test. Brain hippocampus and cortex tissue samples were prepared for whole-genome bisulfite sequencing (WGBS) to generate quantitative DNA methylation datasets in response to repetitive intermittent Xe administration. The resulting WGBS data were evaluated and quantitatively associated with memory recovery. Results: A post-stroke long-term memory outcome model was generated with scaled data using the following inputs: (1) good recovery, (2) moderate recovery, (3) edge, (4) light damage, and (5) severe damage. Differential DNAm 5mC analysis was performed comparing MCAO affected hemisphere with sham and Xe-treated samples. Initial 5mC differential analysis identified 6,175 (Cortex), and 9,037 (Hippocampus) CpG sites that were different between groups. Subsequently the LASSO algorithm was applied and selected 22 CpG sites that correlated with the long-term memory recovery scale. PCA analysis using the 22 CpGs demonstrated separation of memory outcomes. We have also built a predictive linear regression model of the 22 CpGs to assess memory loss or recovery in response to treatment. Analysis showed 7 out of 22 CpGs are conserved in humans (orthologs) for 30 bp regions. Conclusions: Epigenetic 5mC marker panels have the potential for quantitating post-stroke memory damages/recovery.
Interviews of Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) Enrolled in 2 Lisocabtagene Maraleucel (liso-cel) Trials on Their Treatment Experience for 3 Months after Infusion
Authors: Tanya Siddiqi, Ulrich Jaeger, Olga Moshkovich, Julia Braverman, Fei Fei Liu, Sally Lanar, Matthew Miera, Selam Shah, Jennifer Devlen, Gilles Salles
Journal: Blood (2021)
Abstract 11693: When a Parachute Fails: A Rocky Landing to Heart Transplant
Authors: Lua Jafari, Daniel Cruz, Ali Nsair, Michael C Fishbein, Meshe Chonde, Emily Schwitzer, Jessica Zhang, Eric H Yang
Journal: Circulation (2021)

A 71 year-old man with heart failure, porcelain aorta, and mitral regurgitation presented for heart transplant evaluation. He was in cardiogenic shock requiring inotropic support. An echocardiogram showed a dilated left ventricle, severely reduced systolic function, restricted mitral valve leaflet motion, an elevated mean transmitral gradient, and severe mitral regurgitation. The differential of mixed stenotic and regurgitant mitral valve pathology included rheumatic heart disease and congenital mitral valve anomaly. Hemodynamic management of cardiogenic shock in the setting of mixed mitral valve disease presented unique challenges due to a narrow therapeutic window of optimal preload, afterload reduction, inotropic support, and chronotropic control. He was not a candidate for percutaneous mitral valve interventions or surgery. A porcelain aorta made him high risk for vascular complications with mechanical circulatory support. His course was complicated by worsening shock requiring escalation of inotropes, rapid atrial fibrillation, and recurrent episodes of acute pulmonary edema. Ultimately, he underwent an orthotropic heart transplant. A transesophageal echocardiogram at the time of transplant suggested a parachute mitral valve, where all chordae appeared be originating from one papillary muscle. However, additional views revealed the presence of two papillary muscles with asymmetric, shortened anterior chordae and a hypertrophied anterior papillary muscle. Findings were consistent with a rare parachute-like asymmetric mitral valve complicated by mild mitral stenosis and severe mitral regurgitation. Examination of the explanted native heart confirmed these findings.This case highlights: 1) complex management of mixed valvular disease in the setting of cardiogenic shock, 2) echocardiographic evaluation of mixed valvular heart disease, and 3) a rare congenital malformation of a parachute-like mitral valve presenting in adulthood.
Trial in Progress: A Phase 2 Single Arm, Multicenter Trial to Evaluate the Efficacy of the BiTE ® Antibody Blinatumomab (Blincyto) and Vincristine Sulfate Liposomal Injection (Marqibo) in Adult Subjects with Relapsed/Refractory Philadelphia Negative CD19+ Acute Lymphoblastic Leukemia
Authors: David A Rizzieri, Jessica Leonard, Talha Badar, Franklin L. Chen, Bijal D. Shah, Zhiguo Li
Journal: Blood (2021)
Abstract 12207: Impact of Residual Pulmonary Stenosis on the Prognosis After Pulmonary Valve Replacement for Pulmonary Regurgitation
Authors: Yuji Tominaga, Masaki Taira, Takuji Watanabe, Moyu Hasegawa, Takayoshi Ueno, Shigeru Miyagawa, Yoshiki Sawa
Journal: Circulation (2021)

Introduction: Pulmonary valve replacement (PVR) for pulmonary regurgitation (PR) was reported to provide beneficial effects on patients late after repair of tetralogy of Fallot (TOF). However, the impact of the degree of residual pulmonary stenosis (PS) in patients with severe PR remains unclear. Furthermore, the assessment of residual PS was difficult in patients with reduced RVEF. This study aimed to identify the impact of residual PS on the incidence of cardiovascular adverse events after PVR in preserved RVEF (pEF) or reduced RVEF (rEF) patients with PR late after repair of TOF. Methods: This was a single-center, retrospective review of 64 patients (56 repaired TOF-PS and 8 repaired TOF-pulmonary atresia) who underwent PVR for moderate to severe PR between 2003 and 2020. The threshold dividing pEF and rEF was 40%. Regarding residual PS, the definition the pressure gradient at the pulmonary valve in PSR group was 25 mmHg or more and less than 50mmHg. Patients were divided into 4 groups according to RVEF and the degree of residual PS (20 in PR-pEF, 12 in PSR-pEF, 25 in PR-rEF, 7 in PSR-rEF). Cardiovascular adverse events included cardiac death, prosthetic valve dysfunction, arrhythmia requiring treatment, and hospitalization for heart failure. Based on the above, the influence of hemodynamic parameters before PVR was analyzed. Results: The median follow-up period was 6.1 years [interquartile range 2.7-10]. There was no cardiac death and prosthetic valve dysfunction. Two patients died due to non-cardiac reason. Twenty-two (34%) patients showed cardiovascular adverse events. The cardiovascular adverse event-free rates were the highest in PSR-pEF group (100% at 5 years) and the lowest in PSR-rEF group (43% at 5 years) after PVR (log-rank p &amp;lt; 0.01), and 60% in PR-pEF and 70% in PR-rEF. In comparison between PSR groups, PSR-rEF had higher RVEDP (8±2 vs 13±2 mmHg, p &amp;lt; 0.01) and larger RAVI (71±25 vs 105±42 ml/m 2 , p=0.043). Conclusion: Patients with PSR-rEF had a high incidence of cardiovascular adverse events, high RVEDP, and large RAVI, suggesting RV adverse remodeling. The association between the degree of residual PS and RVEF should be taken into consideration on deciding the timing of PVR for PR.
Adverse Prognostic Role of IDH2 Mutations at Diagnosis and during Follow-up in Patients with Acute Myeloid Leukemia and Normal Karyotype
Authors: Erika Borlenghi, Diego Bertoli, Chiara Cattaneo, Margherita Sciumé, Elisa Cerqui, Chiara Pagani, Nicola Bianchetti, Margherita Oberti, Rossella Leopaldo, Cecilia Carbone, Silvana Archetti, Giuseppe Rossi, Alessandra Tucci
Journal: Blood (2021)