tbuckley/cabot-search huggingface dataset:
Invasive Field Radiotherapy Combined with Rituximab Versus Rituximab Alone for Consolidation Therapy in Stage III Follicular Lymphoma Patients Response to R-CHOP Chemotherapy: A Randomized Clinical Study
Authors: Tongyu Lin, He Huang, Xiaoqian Li, Huangming Hong, Liqun Zou, Liling Zhang, Zhihui Zhang, Zhongjun Xia, Yongchang Chen, Meiting Chen, Zegeng Chen, Xiaojie Fang, Hongqiang Guo, Ke Xie, Ying Tian, Suxia Lin, Wei Zhang, Yuyi Yao, Fei Pan, Huawei Weng
Journal: Blood (2021)
Isoform Selective HDAC8 Inhibitor (OCH3) Shows Potency in Selectively Targeting Primary AML Cells
Authors: Amal Mechaal, Amudha Ganapathy, Dolores Mahmud, Taha Y Taha, Rajeev Ranjan, Irum Khan, Pavel Petukhov, Nadim Mahmud
Journal: Blood (2021)
Abstract 9172: Feasibility and Efficacy of Targeted Cardiac NF-kB Inhibition in Experimental Diastolic Dysfunction Using Drug-Delivery Technology: A Proof-of-Concept Study
Authors: Alejandro R Chade, Alfonso Eirin, Gene L Bidwell
Journal: Circulation (2021)

Introduction: Elastin-like polypeptides (ELP) are novel drug delivery vectors that can be fused to therapeutic agents and cell penetrating peptides (CPPs), slowing their plasma clearance and increasing uptake by target tissues. We developed a CPP-ELP fusion to a specific inhibitor of the p50 subunit of NF-kB (SynB1-ELP-p50i). We developed a swine model of chronic kidney disease (CKD) that also fosters hypertension, cardiac remodeling, and diastolic dysfunction, and observed that cardiac abnormalities associate with increased cardiac expression of NF-kB, a ubiquitous transcription factor that modulates cardiac inflammation, fibrosis, and vascular remodeling. Hypothesis: We aimed to define the feasibility and efficacy of intra-coronary (IC) SynB1-ELP-p50i administration to test whether a targeted inhibition of NF-kB can improve cardiac abnormalities in CKD. Methods: We first performed a biodistribution study (BDS) in 3 pigs, 4 hours after IC injection of fluorescently labeled SynB1-ELP-p50i (10 mg/kg). Then, CKD was induced in 6 pigs (bilateral renovascular disease and dyslipidemia), treated with a single IC SynB1-ELP-p50i or placebo at 6 weeks and observed for 8 more weeks. Cardiac morphology and function were quantified before/after treatment by echocardiography. After completion of the studies, pigs were euthanized and hearts excised for ex vivo studies. Results: Using IVIS technology, the BDS showed significant retention of SynB1-ELP-p50i in the heart. In the efficacy study, a single IC administration of IC SynB1-ELP-p50i reduced cardiac NF-kB expression, improved cardiac relaxation, and remodeling compared to untreated CKD (Figure). Conclusions: We show for the first time the feasibility of a targeted inhibition of cardiac NF-kB using ELP technology in a translational model of CKD and diastolic dysfunction. Our study may set the stage for a new therapeutic strategy using unique drug-delivery technology never tested before to protect the heart.
Traction-assisted hybrid endoscopic submucosal dissection for small rectal neuroendocrine tumors
Authors: Takayuki Nasu, Mitsuru Esaki, Yoshihisa Shoguchi, Xiaopeng Bai, Yosuke Minoda, Haruei Ogino, Eikichi Ihara
Journal: Endoscopy (2021)

Endoscopic resection is conducted as a first-line treatment for localized small rectal neuroendocrine tumors (NETs) [1] [2] [3]. However, NETs involve the deep mucosa and submucosa; a sufficient tumor-free vertical margin is required for R0 resection in endoscopic treatment. Recently, we developed the traction-assisted hybrid endoscopic submucosal dissection (ESD) procedure for gastrointestinal tumors [4]. Herein, we present a case of a small rectal NET successfully treated by traction-assisted hybrid ESD ([Video 1]).
Updated Survival and Response Analyses from a Phase 1 Study of Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an <i>IDH1</i> or <i>IDH2</i> Mutation
Authors: Eytan M. Stein, Courtney D. DiNardo, Amir T. Fathi, Alice S. Mims, Michael R. Savona, Anthony S. Stein, Richard M. Stone, Eric S. Winer, Christopher S. Seet, Hartmut Döhner, Daniel A. Pollyea, James K McCloskey, Olatoyosi Odenike, Bob Lowenberg, Gert J. Ossenkoppele, Prapti Patel, Mikhail Roshal, Mark G. Frattini, Frederik Lersch, Salah Nabhan, Caroline Almon, Duygu Saatcioglu, Vickie Zhang, Michael Cooper, Hagop Kantarjian, Martin S. Tallman
Journal: Blood (2021)
Phase 1b Study of Lower-Dose CPX-351 Plus Venetoclax As First-Line Treatment for Patients with AML Who Are Unfit for Intensive Chemotherapy: Preliminary Safety and Efficacy Results
Authors: Geoffrey L. Uy, Vinod A. Pullarkat, Praneeth Baratam, Robert K. Stuart, Stefan Faderl, Vijayalakshmi Chandrasekaran, Qi Wang, Divya Chakravarthy, Ronald S. Cheung, Tara L. Lin
Journal: Blood (2021)
Follow-up Analysis of Ixazomib, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Routine Clinical Practice
Authors: Jiri Minarik, Jakub Radocha, Alexandra Jungova, Jan Straub, Tomas Jelinek, Tomas Pika, Ludek Pour, Petr Pavlicek, Lubica Harvanova, Lenka Capkova, Petra Krhovska, Katerina Machalkova, Pavel Jindra, Ivan Spicka, Hana Plonkova, Martin Stork, Martin Mistrik, Jaroslav Bacovsky, Vladimir Maisnar, Roman Hajek
Journal: Blood (2021)
Characteristics Associated with Disparities in Survival between Hispanic and Non-Hispanic White Patients with Multiple Myeloma: A Matched Cohort Study
Authors: Jing Dong, Zhuping Garacci, Christopher Staffi Buradagunta, Meera Mohan, Anita D'Souza, Ashley Cunningham, Siegfried Janz, Binod Dhakal, Parameswaran Hari
Journal: Blood (2021)
Treatment of Delirium During Critical Illness
Authors: Niall T. Prendergast, Perry J. Tiberio, Timothy D. Girard
Journal: Annual Review of Medicine (2021)

Delirium, an acute disturbance in mental status due to another medical condition, is common and morbid in the intensive care unit. Despite its clear association with multiple common risk factors and important outcomes, including mortality and long-term cognitive impairment, both the ultimate causes of and ideal treatments for delirium remain unclear. Studies suggest that neuroinflammation, hypoxia, alterations in energy metabolism, and imbalances in multiple neurotransmitter pathways contribute to delirium, but commonly used treatments (e.g., antipsychotic medications) target only one or a few of these potential mechanisms and are not supported by evidence of efficacy. At this time, the optimal treatment for delirium during critical illness remains avoidance of risk factors, though ongoing trials may expand on the promise shown by agents such as melatonin and dexmedetomidine.
382 The synthetic long peptide cancer vaccine UV1 in combination with ipilimumab induces a CD4+ Th1 anti-hTERT immune response and an inflammatory tumor microenvironment in patients with melanoma
Authors: Espen Ellingsen, Iliana Kerzeli, Irantzu Anzar, Nadia Mensali, Trevor Clancy, Sara Mangsbo, Steinar Aamdal, Elin Aamdal, Tormod Guren, Else-Marit Inderberg-Suso, Eivind Hovig, Gustav Gaudernack
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Checkpoint inhibitors (CPIs) have revolutionized the treatment of malignant melanoma. Although melanoma patients may experience deep and durable clinical responses to CPI treatment, the majority develop disease progression requiring additional therapy. Combining CPIs with therapeutic cancer vaccines may augment the anti-tumor immune response and thus improve clinical outcomes. UV1 is a therapeutic cancer vaccine based on synthetic antigens derived from the tumor-associated antigen telomerase reverse transcriptase (hTERT). hTERT is activated in 85–90% of all cancers and leads to replication of telomeric DNA, an essential mechanism for increased proliferation, immortality, and invasiveness of cancer cells. In this phase I/IIa study combining UV1 with ipilimumab in patients with melanoma ( NCT02275416 ), we hypothesized that UV1 and ipilimumab might provide synergy in the expansion of vaccine-induced T cells. Furthermore, an augmented CD4+ Th1 immune response targeting a shared tumor antigen may increase T cell infiltration in the tumor microenvironment, promoting immune-mediated cancer cell death. Methods The immune response dynamics were assessed by longitudinal immunomonitoring for up to 5 years using a standard proliferation assay. The phenotype and functionality of vaccine-induced T cells were assessed by patient-derived T cell cloning and subsequent in vitro characterization by flow cytometry, peptide stimulation, and cytokine release assays. On available biopsies harvested at baseline and 12 weeks after treatment initiation, the tumor microenvironment was assessed based on whole-exome sequencing, RNA sequencing, and immunohistochemistry. Results Twelve patients with metastatic melanoma were enrolled in the study and received up to 9 vaccine doses over a 20-week period. A persistent (up to 5 years) vaccine-induced immune responses were demonstrated in 91% of evaluable patients (10/11). Vaccine-specific T cell clones were polyfunctional CD4+ Th1 cells, producing both IFN-γ and TNF-α upon in vitro peptide stimulation. Differential gene expression analysis and immunohistochemical characterization of biopsies at baseline and 12 weeks showed induction of an inflammatory ”hot” tumor microenvironment in clinical responders with available paired biopsies. Conclusions UV1 in combination with ipilimumab leads to robust and long-lasting CD4+ Th1 anti-hTERT immune responses sculpting the local tumor microenvironment. Trial Registration NCT02275416 Ethics Approval The study was approved by Regional Ethical Committee South East (ID number 25 165). The patients provided their written informed consent to participate in the study.
Abstract 9481: Inhibition of Apoptosis and Ferroptosis Signaling Pathways Alleviates Myocardial Ischemia-Reperfusion Injury in Rats Through Modulation of Mitochondrial Function
Authors: Ying Luo, Suchan Liao, Jun Wu, Chayodom Maneechote, Busarin Arunsak, Nattayaporn Apaijai, Juthipong Benjanuwattra, Siriporn Chattipakorn, Nipon Chattipakorn
Journal: Circulation (2021)

Introduction: Apoptosis and ferroptosis have been implicated in cardiac ischemia/reperfusion (I/R) injury. Inhibitors of apoptosis (Z-VAD) and ferroptosis (FER-1) have been shown to protect the heart in several cardiovascular disorders. However, the impacts of Z-VAD, FER-1, and combined therapy during cardiac I/R injury have not been elucidated. Hypothesis: Z-VAD and FER-1 provide cardioprotection by reducing myocardial cell injury and improving cardiac function. The combined treatment exerts better benefits than either single regimen. Methods: Male rats (n=25) were equally divided into 5 groups: sham, vehicle, Z-VAD at 3.3 mg/kg, FER-1 at 2 mg/kg, and combined FER-1 and Z-VAD. All treatments were intravenously injected to the rats 15 min before ischemia. Left anterior descending coronary was ligated for 30 min, followed by 120-min reperfusion in all animals except the sham group. Left ventricular ejection fraction (LVEF), infarct size, mitochondrial reactive oxygen species (ROS) production, and protein expressions of apoptosis and ferroptosis were determined. Results: Cardiac I/R injury led to cardiac mitochondrial dysfunction and cell death, contributed to infarct size expansion and LV dysfunction (Fig 1A-D). Z-VAD, FER-1 and combined treatments markedly increased %LVEF, reduced ROS levels and infarct size (the %reduction is 42.9%, 41.4%, and 47.7%, respectively, compared with vehicle). Cleaved caspase 3 (apoptosis) and ACSL4 (ferroptosis) expression levels were also reduced in those rats. The combined treatment did not show a significant advantage, compared with either single regimen (Fig 1A-D). Conclusions: Inhibitors of either apoptosis or ferroptosis similarly reduced cardiac mitochondrial dysfunction, apoptosis and ferroptosis, resulting in decreased infarct size, and finally leading to improved LV function. These findings indicate that ferroptosis could be a novel therapeutic target for cardioprotection in cardiac I/R injury.
A novel C-terminal heat shock protein 90 inhibitor that overcomes STAT3-Wnt-β-catenin signaling-mediated drug resistance and adverse effects
Authors: Ho Jin Lee, Hye-Young Min, Young-Sik Yong, Jihyae Ann, Cong Truong Nguyen, Minh Thanh La, Seung Yeob Hyun, Huong Thuy Le, Hyewon Kim, Hyukjin Kwon, Gibeom Nam, Hyun-Ju Park, Jeewoo Lee, Ho-Young Lee
Journal: Theranostics (2021)

The heat shock protein (Hsp) system plays important roles in cancer stem cell (CSC) and non-CSC populations. However, limited efficacy due to drug resistance and toxicity are obstacles to clinical use of Hsp90 inhibitors, suggesting the necessity to develop novel Hsp90 inhibitors overcoming these limitations.
<i>In Situ</i> Vaccination with Combination of Class B and Class C Toll-like Receptor 9 Agonist CpG Immune Adjuvant Nanoparticles to Induce a Systemic Anti-Lymphoma Response
Authors: Adam Yuh Lin, Jonathan Scott Rink, Colby Shad Thaxton, Leo I. Gordon
Journal: Blood (2021)
Use of Transtracheal Oxygen following Decannulation of Pediatric Tracheostomy
Authors: Ujjwal Kumar Chowdhury
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Purpose: Uninterrupted sustained oxygenation is paramount in neonates and infants with cyanotic/acyanotic congenital heart diseases (CHD) undergoing closed or open heart surgeries and tracheostomy tube decannulation to avoid hypoxic events. Description: We describe here-in a new device, permitting uninterrupted delivery of oxygen through the tracheostomy stoma, allowing continuation of enteral feeds and suctioning of the endotracheal secretions through the tracheostomy stoma. Evaluation: Eighty-four neonates and infants with a median age of four months (IQR:23 days-9 months) undergoing different closed and open heart surgeries for cyanotic/acyanotic CHD with or without pulmonary arterial hypertension were treated with a device permitting uninterrupted oxygenation following tracheostomy tube decannulation. There were 11 (13.1%) deaths due to multifactorial etiologies, and one was lost to follow-up. Seventy-two children were successfully decannulated using this protocol. At a median follow-up of 166(IQR:82.5-216) months, the actuarial survival was 86.61% (SE±0.04%; 95% CI: 77.1-92.3). Conclusions: Transtracheal oxygenation through the tracheostomy stoma via a thin catheter allows uninterrupted oxygenation following tracheostomy tube decannulation, continuation of enteral feeds, and allows intermittent endotracheal suctioning, thus avoiding post decannulation hypoxic events.
Progression Free Survival (PFS) Analysis of Daratumumab (Dara), Cyclophosphamide, Thalidomide and Dexamethasone: A Quadruplet Intensified Treatment for Transplant Eligible Newly Diagnosed Multiple Myeloma (TE NDMM) Patients
Authors: Edvan De Queiroz Crusoe, Joanna Leal, Marco Aurelio Salvino, Larissa Ferreira Lucas, Juliana Andrade Santos, Herbert Henrique de Melo Santos, Alessandro de M. Almeida, Allan de souza Santos, Marcos Chaves, Mariane Melo Santos, Sarah Queiroz Silva, Lucas de Oliveira Vieira, Cleverson Alves Fonseca, Elisangela Adorno, Vania Hungria, Maria da Gloria B. Arruda
Journal: Blood (2021)
Consensus core clinical data elements for meningiomas (v2021.1)
Authors: Farshad Nassiri, Justin Z Wang, Karolyn Au, Jill Barnholtz-Sloan, Michael D Jenkinson, Kate Drummond, Yueren Zhou, James M Snyder, Priscilla Brastianos, Thomas Santarius, Suganth Suppiah, Laila Poisson, Francesco Gaillard, Mark Rosenthal, Timothy Kaufmann, Derek S Tsang, Kenneth Aldape, Gelareh Zadeh
Journal: Neuro-Oncology (2021)

Abstract Background With increasing molecular analyses of meningiomas, there is a need to harmonize language used to capture clinical data across centers to ensure that molecular alterations are appropriately linked to clinical variables of interest. Here the International Consortium on Meningiomas presents a set of core and supplemental meningioma-specific common data elements (CDEs) to facilitate comparative and pooled analyses. Methods The generation of CDEs followed the 4-phase process similar to other National Institute of Neurological Disorders and Stroke (NINDS) CDE projects: discovery, internal validation, external validation, and distribution. Results The CDEs were organized into patient- and tumor-level modules. In total, 17 core CDEs (10 patient level and 7 tumor level) as well as 14 supplemental CDEs (7 patient level and 7 tumor level) were defined and described. These CDEs are now made publicly available for dissemination and adoption. Conclusions CDEs provide a framework for discussion in the neuro-oncology community that will facilitate data-sharing for collaborative research projects and aid in developing a common language for comparative and pooled analyses. The meningioma-specific CDEs presented here are intended to be dynamic parameters that evolve with time and The Consortium welcomes international feedback for further refinement and implementation of these CDEs.
Abstract 8955: Cardiopulmonary Phenotyping of Sex-Based Differences in a Feline Model of HFpEF
Authors: Deborah M Eaton, Remus M Berretta, Jacqueline E Lynch, Joshua G Travers, Kathleen C Woulfe, Ryan D Pfeiffer, Michelle L Hulke, Alexander R Hobby, Giana Schena, Jaslyn P Johnson, Markus Wallner, Nathan R Tucker, Timothy A McKinsey, Marla R Wolfson, Steven R Houser
Journal: Circulation (2021)

Introduction: Approximately 50% of all heart failure (HF) diagnoses can be classified as HF with preserved ejection fraction (HFpEF), which has no FDA approved therapies. HFpEF is more prevalent in females compared to males, but the underlying mechanisms for the development as a sex-based disorder are unknown. We previously described how slow progressive pressure overload (PO) in male felines recapitulates the HFpEF phenotype but have not investigated the female phenotype. Hypothesis: Females will develop a less severe HFpEF phenotype compared to males under the same pathological stress. Methods &amp; Results: Male (m) and female (f) domestic short felines (age 2mo) underwent aortic constriction (m: n=11; f: n=10) using a customized pre-shaped band or a sham procedure (m: n=7; f: n=7). Before surgery (baseline), there was no difference in body weight (BW) between groups and lung compliance was not different. Echocardiography revealed no significant difference in the ratio of left atrium to aortic root (LA/Ao), LA ejection fraction (LA EF), left ventricle (LV) ejection fraction, LV wall-thickness, and E/A ratio. By 4mo post-surgery, both males and females had developed cardiac dysfunction and decreased lung compliance. At this time, females had significantly smaller BWs than males. Despite the difference in BW, LV wall thickness and changes in E/A ratio were similar in both sexes in banded vs. shams. Importantly, LV EF did not change in any group. There was a decrease in LA EF and increased LA/Ao in all banded animals. Invasive hemodynamics at 4mo post-surgery showed no differences between sexes for the systolic pressure gradient generated by aortic banding. Banded males had higher LV end-diastolic pressure vs. banded females (m: 15.0±2.7mmHg; f: 8.1±1.9mmHg). However, there was a trend towards prolongation of tau and lower dp/dt min in banded females, suggestive of abnormal relaxation. There were no differences between banded males and females in heart weight/BW or cardiomyocyte cross-sectional area and both developed fibrosis. Conclusions: Exposure of male and female felines to PO resulted in similar cardiac hypertrophy, fibrosis, and decreased lung compliance. Females had lower LVEDP than males suggesting they may be protected from diastolic dysfunction.
Concurrent Monitoring of Peripheral Blood Circulating Tumor DNA and Circulating Tumor Cells in Relapsed/Refractory Follicular Lymphoma Patients Post Axicabtagene Ciloleucel, a Single Center Experience
Authors: Sameh Gaballa, Julio C. Chavez, Michael D. Jain, Meghan A Menges, Kayla M Reid, David Kaldas, Bijal D. Shah, Marco L. Davila, Frederick L. Locke
Journal: Blood (2021)
Therapeutic and Immunologic Responses Elicited By <i>in Situ</i> Vaccination with CpG, Ibrutinib, and Low-Dose Radiation
Authors: Tanaya Shree, Sarah Haebe, Debra K. Czerwinski, Grady Day, Anuja Sathe, Michael S. Khodadoust, Matthew J. Frank, Sara Beygi, Richard Hoppe, Steven R. Long, Brock Martin, Hanlee P. Ji, Ronald Levy
Journal: Blood (2021)
The Eatl-001 Trial: Results of a Phase 2 Study of Brentuximab Vedotin and CHP Followed By Consolidation with High-Dose Therapy - Autologous Stem-Cell Transplantation (HDT-ASCT) in the Frontline Treatment of Patients with Enteropathy-Associated T-Cell Lymphoma
Authors: David Sibon, Sherine Khater, Julie Bruneau, Chantal Brouzes, Ludovic Lhermitte, Thierry Jo Molina, Guillaume Cartron, Veronique Morel, Georgia Malamut, Adrien Chauchet, Franck Morschhauser, Baptiste Perard, Jean-Michel Boulet, Anne-Cécile Gauchy, Nadine Cerf-Bensussan, Elizabeth A. Macintyre, Vahid Asnafi, Christophe Cellier, Olivier Hermine
Journal: Blood (2021)
Magnetic resonance linear accelerator technology and adaptive radiation therapy: An overview for clinicians
Authors: William A. Hall, Eric Paulson, X. Allen Li, Beth Erickson, Christopher Schultz, Alison Tree, Musaddiq Awan, Daniel A. Low, Brigid A. McDonald, Travis Salzillo, Carri K. Glide‐Hurst, Amar U. Kishan, Clifton D. Fuller
Journal: CA A Cancer Journal for Clinicians (2021)

Abstract Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process. This enables the adaptation of the irradiated volume to account for changes in organ and/or tumor position, movement, size, or shape that may occur over the course of treatment. The advantages and challenges of ART maybe somewhat abstract to oncologists and clinicians outside of the specialty of radiation oncology. ART is positioned to affect many different types of cancer. There is a wide spectrum of hypothesized benefits, from small toxicity improvements to meaningful gains in overall survival. The use and application of this novel technology should be understood by the oncologic community at large, such that it can be appropriately contextualized within the landscape of cancer therapies. Likewise, the need to test these advances is pressing. MR‐guided ART (MRgART) is an emerging, extended modality of ART that expands upon and further advances the capabilities of ART. MRgART presents unique opportunities to iteratively improve adaptive image guidance. However, although the MRgART adaptive process advances ART to previously unattained levels, it can be more expensive, time‐consuming, and complex. In this review, the authors present an overview for clinicians describing the process of ART and specifically MRgART.
Oral Ixazomib in Untreated Follicular Lymphoma Permits COVID-19 Vaccine Response and Its Efficacy Is Associated with Clinical Factors and Gene Expression Signatures
Authors: Solomon A. Graf, Ryan C. Lynch, Chaitra S. Ujjani, Ted A Gooley, David G. Coffey, Andrew J. Cowan, Stephen D. Smith, Mazyar Shadman, Edus H. Warren, Edward Libby, Colin D. Godwin, Alexander L Greninger, Jonathan R. Fromm, Ajay K Gopal
Journal: Blood (2021)
An Update on Outcomes Using the USC ALL Frontline Regimen (based on CCG-1882) after Further Modification of Protocol in the Era of Novel Agents in Ph-Negative ALL Patients; A Retrospective Study
Authors: Vincent Louie Mendiola, Catherine Ly, Thuy Bui, Jennifer Wang, Jack Rodman, Maria E. Vergara-Lluri, Karrune Woan, Eric Tam, Preet M. Chaudhary, Dan Douer, Abdullah Ladha, George Yaghmour
Journal: Blood (2021)