tbuckley/cabot-search huggingface dataset:
Abstract 13645: Contemporary Propensity-Matched Analysis Reveals Alarmingly High Risk Of Mortality, Arrhythmia And Cardiac Arrest In Nationwide Hospitalizations Of Patients With Heart Failure With Preserved Ejection Fraction And Cannabis Use Disorder
Authors: Sonali Sachdeva, Arashpreet Chhina, Rashmi Gawde, Naima A Rahim, Geethu Jnaneswaran, Athul Raj Raju, , Neha, Zainab Gandhi, Rupak Desai
Journal: Circulation (2021)

Background: Preliminary reports have suggested a link between cannabis use and heart failure (HF); however, with inconclusive literature on the subject, there exists an unmet need for contemporary data on outcomes of HF patients with cannabis use. The rising prevalence of Heart Failure with Preserved Ejection Fraction (HFpEF) incited us to assess the impact of cannabis use disorder (CUD) on in-hospital outcomes of HFpEF using nationwide multicenter data. Methods: Adult admissions related to HFpEF with vs. without CUD were identified using the National Inpatient Sample (Oct 2015-Dec 2017). Demographically matched cohorts, HFpEF-CUD+ vs. HFpEF-CUD-, were obtained and compared for comorbidities and in-hospital outcomes. Multivariable regression analyses were performed after controlling for confounders (demographic/hospital characteristics, comorbidities and substance abuse) to assess the risk of adverse outcomes including all-cause mortality, arrhythmia (atrial fibrillation/flutter, ventricular arrhythmia &amp; cardiac arrest) and stroke. Results: Of 3,835,473 HFpEF-related admissions, 10980 (0.3%) patients were cannabis users. Matched cohorts, CUD+ and CUD- were comparable for demographics (median age 55 vs. 54 years, &gt;60% male, &gt;80% white/black). The CUD+ cohort had a lower rate of comorbidities including hypertension (87.5% vs 88.5%), diabetes (33.7% vs 43.7%), hyperlipidemia (38.4% vs 42.1%), obesity (26.7% vs 36.2%), and renal failure (32.8% vs 39.8%) (Table 1). Despite a lower comorbidity burden, the CUD+ cohort was often admitted non-electively (95.2% vs. 92.8%) and had considerably higher odds of all-cause mortality (aOR 2.24, 95%CI:1.81-2.78), arrhythmia (aOR 1.15, 95%CI:1.05-1.25) and cardiac arrest (aOR 3.87, 95%CI: 2.88-5.21) (p&lt;0.05) (Fig. 1). Conclusions: This nationwide multicenter analysis revealed HFpEF admissions in patients with CUD had a significantly higher risk of adverse in-hospital outcomes despite a lower CVD risk.
CD70 Expression in Mature T-Cell Lymphomas
Authors: Mario L. Marques-Piubelli, Luisa Solis Soto, Swaminathan Padmanabhan Iyer, Jason Sagert, Minh Thu Pham, Kimberly Tipton, Wei Lu, Khaja B Khan, Leticia G Hamana Zorrilla, Jennifer R Chapman, Beenu Thakral, Jie Xu, Roberto N. Miranda, Kristofer Jennings, Francisco Vega
Journal: Blood (2021)
Efficacy of Interventions to Prevent Physical and Sexual Dating Violence Among Adolescents
Authors: Antonio Piolanti, Heather M. Foran
Journal: JAMA Pediatrics (2021)

Sexual and physical dating violence is prevalent among adolescents and is associated with adverse health effects.To conduct a systematic review and meta-analysis of randomized clinical trials to assess the efficacy of prevention programs for sexual and physical dating violence in adolescents.Search terms were combined for dating violence, adolescents, and randomized clinical trials in PsycINFO/Eric/PsycArticles, PubMed, and Web of Science databases from inception through April 2021.Included studies had a randomized design of any type examining the efficacy of an intervention to reduce dating violence among adolescents and provided at least 1 measure of sexual or physical dating violence.Data extraction coded characteristics of trials, participants, and interventions and assessed risk of bias using the Revised Cochrane Collaboration Risk of Bias tool. Outcomes were pooled using a random-effects model. Subgroup and meta-regression analyses were performed to explore the target population and intervention factors associated with positive outcomes.The odds ratio (OR) was calculated for 3 different outcomes: (1) sexual dating violence, (2) physical dating violence, and (3) composite measures of sexual and physical dating violence. For each outcome, separate analyses were conducted for survivorship and perpetration scores. We also combined the scores of physical/sexual violence and perpetration/survivorship of teen dating violence into a single composite overall outcome including all studies.Eighteen trials (22 781 adolescents) were included. Overall, interventions were associated with reduced physical and sexual dating violence (OR, 0.78; 95% CI, 0.69-0.89; P < .001). Separate analyses further indicated that this association was significant for physical violence perpetration (OR, 0.74; 95% CI, 0.59-0.92; P = .01) and survivorship (OR, 0.78; 95% CI, 0.64-0.95; P = .01). For sexual violence, the association was not statistically significant. Exploratory subgroup analyses revealed that trials targeting at-risk youth, older adolescents (age >15 years), and trials involving parents in the intervention reported significantly larger effect sizes. Meta-regression analyses did not show any significant associations between intervention effect sizes and length or intensity of the programs. Publication bias was observed, but the adjusted ORs remained significant. Three studies reported iatrogenic associations.Findings from this study suggest that prevention programs may be effective in reducing physical teen dating violence, but there is unclear evidence of the effect on sexual violence outcomes. Further research assessing the active ingredients of interventions, especially in the area of sexual dating violence, is warranted.
Mavorixafor, an Oral CXCR4 Antagonist, for Treatment of Patients with WHIM Syndrome: Results from the Long-Term Extension of the Open-Label Phase 2 Study
Authors: David C. Dale, Frank Caleb Firkin, Audrey Anna Bolyard, Weihua Tang, Honghua Jiang, Richard MacLeod, Diego Cadavid, Yanping Hu
Journal: Blood (2021)
NIMG-46. SYSTEMATIC LITERATURE REVIEW OF ARTIFICIAL INTELLIGENCE ALGORITHMS USING PRE-THERAPY MR IMAGING FOR GLIOMA MOLECULAR SUBTYPE CLASSIFICATION
Authors: Jan Lost, Tej Verma, Niklas Tillmanns, W R Brim, Harry Subramanian, Ichiro Ikuta, Richard Bronen, William Zucconi, Ming Lin, Khaled Bousabarah, Michele Johnson, Jin Cui, Ajay Malhotra, Michael Sabel, Mariam Aboian
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Identifying molecular subtypes in gliomas has prognostic and therapeutic value, traditionally after invasive neurosurgical tumor resection or biopsy. Recent advances using artificial intelligence (AI) show promise in using pre-therapy imaging for predicting molecular subtype. We performed a systematic review of recent literature on AI methods used to predict molecular subtypes of gliomas. METHODS Literature review conforming to PRSIMA guidelines was performed for publications prior to February 2021 using 4 databases: Ovid Embase, Ovid MEDLINE, Cochrane trials (CENTRAL), and Web of Science core-collection. Keywords included: artificial intelligence, machine learning, deep learning, radiomics, magnetic resonance imaging, glioma, and glioblastoma. Non-machine learning and non-human studies were excluded. Screening was performed using Covidence software. Bias analysis was done using TRIPOD guidelines. RESULTS 11,727 abstracts were retrieved. After applying initial screening exclusion criteria, 1,135 full text reviews were performed, with 82 papers remaining for data extraction. 57% used retrospective single center hospital data, 31.6% used TCIA and BRATS, and 11.4% analyzed multicenter hospital data. An average of 146 patients (range 34-462 patients) were included. Algorithms predicting IDH status comprised 51.8% of studies, MGMT 18.1%, and 1p19q 6.0%. Machine learning methods were used in 71.4%, deep learning in 27.4%, and 1.2% directly compared both methods. The most common algorithm for machine learning were support vector machine (43.3%), and for deep learning convolutional neural network (68.4%). Mean prediction accuracy was 76.6%. CONCLUSION Machine learning is the predominant method for image-based prediction of glioma molecular subtypes. Major limitations include limited datasets (60.2% with under 150 patients) and thus limited generalizability of findings. We recommend using larger annotated datasets for AI network training and testing in order to create more robust AI algorithms, which will provide better prediction accuracy to real world clinical datasets and provide tools that can be translated to clinical practice.
Abstract 13647: Genetic Deletion of Interleukin-22 Prevents Angiotensin II-Induced Cardiac Diastolic Dysfunction in Mouse
Authors: Mai Yamamoto, Hideo Yasukawa, Jinya Takahashi, Shoichiro Nohara, Tomoko Minami, Tatsuhiro Shibata, Toshiyuki Yanai, Kota Okabe, Daiki Akagaki, Yoshihiro Fukumoto
Journal: Circulation (2021)

Introduction: Interleukin-22 (IL-22) is a member of the IL-10 cytokine family, which promotes STAT3 activation in targets cells. Although it has been shown that persistent activation of STAT3 causes myocardial hypertrophy and fibrosis, little is known about the effect of IL-22 in the pathogenesis of cardiac diastolic dysfunction. Hypothesis: We hypothesized that IL-22 would be a factor that cardiac diastolic dysfunction. Methods and Results: We used angiotensin II (AngII) infusion mouse model, which has been reported to increase serum IL-22 levels, to cause cardiac diastolic dysfunction. We first investigated the effect of IL-22 deletion to cardiac function. Wild-type (WT) mice and IL-22 deficient (IL-22 KO) mice were compared cardiac function after 2 weeks AngII infusion. Echocardiographic analysis showed no decrease in systolic function as indicated by EF in both groups. However, In WT mice, E/e' was significantly increased compared to before AngII infusion. In contrast to WT mice, E/e' was not increased in IL-22KO mice by AngII infusion. These results suggested that AngII- induced cardiac diastolic dysfunction was prevented in IL-22KO mice. Next, we analyzed the effect of IL-22 deletion to histological changes. Compared to WT mice, ventricular weight to body weight ratio was significantly smaller in IL-22KO mice after 2 weeks AngII infusion. Echocardiographic analysis also showed that ventricular wall thickness was suppressed in IL-22KO mice. Sirius red staining revealed no difference in myocardial fibrosis between WT mice and IL-22KO mice after 2weeks AngII infusion. Conclusions: These results suggest that IL-22 plays an important role in the pathogenesis of AngII- induced cardiac diastolic dysfunction and cardiac hypertrophy.
Changes in household food and drink purchases following restrictions on the advertisement of high fat, salt, and sugar products across the Transport for London network: a controlled interrupted time series analysis
Authors: Amy Yau, Nicolas Berger, Cherry Law, Laura Cornelsen, Robert Greener, Jean Adams, Emma J Boyland, Thomas Burgoine, Frank de Vocht, Matt Egan, Vanessa Er, Amelia A Lake, Karen Lock, Oliver Mytton, Mark Petticrew, Claire Thompson, Martin White, Steven Cummins
Journal: The Lancet (2021)
Abstract 11358: A Standardized Heart Failure Bundle to Provide Better Patient Care and Reduce Readmissions
Authors: Tara Torres, Diane Collins
Journal: Circulation (2021)

In adults, heart failure (HF) is associated with increased morbidity and mortality, with projected health care costs of 70 billion by 2030. Evidence-based care identifies that early evaluation and management improves lives and is cost-effective. Streamlining strategies to facilitate care delivery can assist heart failure patients in sustaining their complex lifestyles and behavioral modifications while preventing readmissions. Utilizing a standardized heart failure bundle with evidence-based heart failure care across health systems can provide better care and reduce the 30-day readmission rate. An interdisciplinary team identified a shared need and worked together to set the patient up for success providing a seamless transition of care from inpatient to outpatient. A literature review of evidence-based heart failure care was completed. An Information Systems (IS) team was engaged in creating an HF dashboard to measure interventions and show a return of investments. A Physician Champion was brought into the team to lead the group. A nurse coordinates the initiative while ensuring all aspects are met before discharge. The bundle includes standardized patient education, pharmacy medication reconciliation (MR) before discharge, medication counseling, and HF clinic visit within 10-days of discharge.The Standardized HF bundle begins with identifying heart failure admissions utilizing a readmissions risk report. Next, ensuring medication reconciliation is completed before discharge, as well as medication counseling. A self-management tool engaged patients in care as well. Finally, ensuring the patient has a follow-up appointment within 14 days of discharge. Process metrics evaluated include scheduling and completing follow-up (F/U) appointments and completing medication reconciliation by pharmacy. Before the HF bundle, 72% of F/U appointments were scheduled, and 34.3% were completed in March 2020. MR was 55%. After the HF bundle’s implementation, 95.9% of f/U appointments were scheduled, and 69.2% were completed in March 2021. In addition, mr was 77%. The Outcomes data includes HF readmission rates. The HF readmission rates were 30.4% in early 2020. After the implementation of the HF bundle, the HF readmission rate is 18.5%.
Pembrolizumab Added to First-Line Cyclophosphamide, Bortezomib and Dexamethasone in Newly Diagnosed Transplant Non-Eligible Myeloma Patients: A Phase 2A Open Label, Multi Centre Study
Authors: Rami Kotb, Engin Gul, Nizar Abdel-Samad, Ibraheem Othman, Michel Pavic, Donna E. Reece
Journal: Blood (2021)
Nano-designed CO donor ameliorates bleomycin-induced pulmonary fibrosis via macrophage manipulation
Authors: Chunyu Guo, Cheng Zhang, Zhengmei Xia, Bingdong Song, Weirong Hu, Yingying Cui, Yanni Xue, Mizhen Xia, Dexiang Xu, Shichen Zhang, Jun Fang
Journal: Journal of Controlled Release (2021)
Neutrophil Cyto‐Pharmaceuticals Suppressing Tumor Metastasis via Inhibiting Hypoxia‐Inducible Factor‐1<i>α</i> in Circulating Breast Cancer Cells
Authors: Ying Zhang, Cong Wang, Weishuo Li, Wei Tian, Chunming Tang, Lingjing Xue, Ziming Lin, Guilai Liu, Dongfei Liu, Ying Zhou, Qianqian Wang, Xu Wang, Lutz Birnbaumer, Yong Yang, Xianjing Li, Caoyun Ju, Can Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract Circulating tumor cells (CTCs) are reported as the precursor of tumor metastases, implying that stifling CTCs would be beneficial for metastasis prevention. However, challenges remain for the application of therapies that aim at CTCs due to lack of effective CTC‐targeting strategy and sensitive therapeutic agents. Herein, a general CTC‐intervention strategy based on neutrophil cyto‐pharmaceuticals is proposed for suppressing CTC colonization and metastasis formation. Breast cancer 4T1 cells are infused as the mimic CTCs, and 4T1 cells trapped are first elucidated in neutrophil extracellular traps (NETs) expressing high levels of hypoxia‐inducible factor‐1 α (HIF‐1 α ) due to NET formation and thus promoting tumor cell colonization through enhanced migration, invasion and stemness. After verifying HIF‐1 α as a potential target for metastasis prevention, living neutrophil cyto‐pharmaceuticals (CytPNEs) loaded with HIF‐1 α inhibitor are fabricated to therapeutically inhibit HIF‐1 α . It is demonstrated that CytPNEs can specially convey the HIF‐1 α inhibitor to 4T1 cells according to the inflammatory chemotaxis of neutrophils and down‐regulate HIF‐1 α , thereby inhibiting metastasis and prolonging the median survival of mice bearing breast cancer lung metastasis. The research offers a new perspective for understanding the mechanism of CTC colonization, and puts forward the strategy of targeted intervention of CTCs as a meaningful treatment for tumor metastasis.
CSIG-22. Cd95l/Cd95 GENE DELETION DECREASES MOUSE GLIOMA TUMORIGENESIS THROUGH THE INHIBITION OF NON-CANONICAL CD95L/CD95-MEDIATED CELL GROWTH AND IMMUNOSUPPRESSION
Authors: Clara Quijano-Rubio, Michael Weller
Journal: Neuro-Oncology (2021)

Abstract CD95 is a transmembrane receptor with potential to promote both cell death and growth. Initially described to trigger apoptosis upon ligand (CD95L) engagement, CD95 may also prompt cell proliferation, invasion and stemness. CD95 stimulation to induce cancer cell apoptosis has been proved clinically impracticable. However, in tumors expressing both CD95 and CD95L, strategically inhibiting CD95-CD95L interactions to simultaneously block cancer cell growth and apoptotic cell death in tumor microenvironment components, including CD95-expressing antitumor immune effector cells, may represent an alternative therapeutic strategy. Here we characterized the expression of CD95 and CD95L in murine glioma models in vitro and in vivo. To fully disrupt CD95-CD95L interactions, we deleted Cd95 or Cd95l by CRISPR-Cas9-mediated knockout (KO) and assessed the consequences on cell growth and tumorigenicity in immunocompetent and immunocompromised mice. CD95 expression was identified in selected murine glioma cell lines. In vitro, expression of the canonical, membrane-bound, form of CD95L was not detected but cell lines expressed a shorter non-canonical, soluble, Cd95l variant. Tumors generated upon implantation of the same cells in vivo expressed both Cd95l variants. Upon Cd95l KO, all investigated cell lines exhibited reduced growth in vitro. Cell growth reduction upon Cd95 KO in SMA-497 murine glioma cells was rescued upon Cd95 re-transfection, validating CD95 specificity of the phenotype. Cd95-overexpression in Cd95-expressing cells did not increase growth. In vivo, Cd95 or Cd95l KO cell implantation in syngeneic mice generated smaller tumors than wildtype cells, resulting in prolonged survival. While 40% Cd95l KO cell-implanted immunocompetent mice did not develop tumors, all immunodeficient mice did. Altogether, these data reveal a growth-promoting role of non-canonical CD95L-CD95 interactions in murine gliomas, which blockade through gene KO results in decreased tumorigenicity. Furthermore, our data suggest the contribution of CD95L-mediated immunosuppression to the reduction of Cd95l KO-associated tumorigenicity.
A Phase I Study of Asciminib (ABL001) in Combination with Dasatinib and Prednisone for BCR-ABL1-Positive ALL in Adults
Authors: Marlise R. Luskin, Kristen E. Stevenson, Lourdes M. Mendez, Eunice S. Wang, Martha Wadleigh, Jacqueline S. Garcia, Richard M. Stone, Hyun Hwan An, Ella Hagopian, Ilene Galinsky, Lindsey Rae, Rebecca Leonard, Daniel J. DeAngelo, Mark A. Murakami
Journal: Blood (2021)
Abstract 12874: Impact of Calcified Nodule in Patients Undergoing Rotablator Atherectomy
Authors: Ploy Pengchata, Nattawut Wongpraparut, Namthip Wongsawangkit, Rungtiwa Pongakasira
Journal: Circulation (2021)

Introduction: Impact on clinical outcome of the patient with calcified nodule remain unknown. Calcified nodule may cause suboptimal stent expansion, stent mal-apposition. Hypothesis: We hypothesized that the presence of calcified nodule in the heavy calcified lesion undergoing rotablator atherectomy (RA) assisted percutaneous coronary intervention (PCI) increased device-oriented composite endpoint (DoCE). Methods: We retrospective reviewed consecutives patient with heavy calcified lesion underwent RA assisted intravascular ultrasound (IVUS) guidance PCI between August 2016-April 2020. Pre-procedural IVUS imaging was mandatory. Calcified nodule was defined as convex shape of luminal surface and luminal side of calcium with protruding in the coronary artery lumen that assessed by IVUS. Primary outcome was cumulative 5-year composite device-oriented composite endpoint (DoCE), define as composite of CV death, myocardial infarction and clinically-driven target lesion revascularization (CDTLR). Results: Two-hundred consecutives patient with heavy calcified lesion underwent RA assisted intravascular ultrasound (IVUS) guidance PCI was enrolled. Calcified nodule was found in 87 patients (43.5%) with heavily calcified lesions. Cumulative 5-year DoCE was significantly higher in the presence of calcified nodule group than in the non-calcified nodule group (20.7% vs 8.8%, P=0.02). Calcified nodule group has the higher incidence of under-expansion and asymmetrical expansion of stent. The patient who had calcified nodule with eccentric calcification has significantly higher cumulative 5-year DoCE compared to calcified nodule with concentric calcification (p&lt;0.01). Conclusions: The presence of calcified nodule in the heavily calcified lesion underwent RA assisted PCI increased with cumulative 5-year DoCE.
EXTH-52. SYSTEMIC AND BRAIN PHARMACOKINETICS OF THE AMP-ACTIVATED PROTEIN KINASE SELECTIVE INHIBITOR SBI-0206965 AS A POTENTIAL THERAPEUTIC AGENT FOR THE TREATMENT OF GLIOBLASTOMA MULTIFORME
Authors: Janki Desai, Mruniya Gawali, Aniruddha Karve, Gary Gudelsky, Larry Sallans, Biplab Dasgupta, William Seibel, Pankaj Desai
Journal: Neuro-Oncology (2021)

Abstract PURPOSE AMP-activated protein kinase (AMPK) is a molecular hub for cellular metabolic control. Recent evidence suggests that AMPK is a “druggable” novel target for the treatment of Glioblastoma Multiforme (GBM). However, AMPK-inhibitory compounds are largely limited to compound C, which has a poor selectivity profile. SBI-0206965 is a diaminopyrimidine derivative that directly inhibits AMPK with 40-fold greater potency and markedly lower kinase promiscuity than compound C. The current studies provide insights into systemic pharmacokinetics and plasma to brain partitioning of SBI-0206965. METHODS We conducted an intracerebral microdialysis study employing jugular vein-cannulated Sprague Dawley rats (males, 6- 8 weeks). Serial brain extracellular fluid (ECF) and venous blood samples were collected up to 10 hrs following intraperitoneal administration of SBI-0206965 (25 mg/kg). These samples were then quantitated for SBI-0206965 levels using a LC/MS method (Thermo Scientific LTQ-FT™, Ionization: Electrospray Ionization; positive ion). PK analysis was performed using the Non–Compartmental Analysis (Phoenix® WinNonlin 8.2 Certara USA, Inc.). RESULTS Plasma and ECF peak concentrations (Cmax) were 7.15 µM and 0.68 µM, whereas the time to peak (Tmax) were 0.5 and 1 hr, respectively. The plasma and brain ECF elimination half-lives were 1.5 and 3 hours, respectively. Plasma protein binding of SBI-0206965 was 82%. A comparison of the brain ECF Cmax and area under the curve (AUC) to corresponding plasma values suggested that the brain partitioning of the compound was 10-18%. When corrected for unbound fraction in plasma the AUC ratio was 0.86. Thus, these studies show that SBI-0206965 has adequate brain penetration. Further studies are now in progress to assess selectivity of SBI-0206965 for AMPK expressing cell lines, efficacy against patient-derived GBM and PK in tumor-bearing mice. CONCLUSION Results from this study will help to design optimal dosing regimen of SBI-0206965 in our efforts to explore AMPK as a GBM-specific drug target.