tbuckley/cabot-search huggingface dataset:
Abstract 10311: Increasing Inpatient Palliative Care Referrals for Veterans with Heart Failure: A Quality Improvement Initiative
Authors: Jadry Gruen, Naseema Merchant, Sarah Gillespie-Heyman, Tracy Shamas, Samuel Adelman, Margaret Bauer, Andrea Ruskin, Parul Gandhi
Journal: Circulation (2021)

Background: Heart failure (HF) portends significant morbidity and mortality. Integrating palliative care (PC) with HF management may improve quality of life, communication, and preparedness planning. At the VA hospital in West Haven, CT, PC was utilized in 6.5% of patients admitted with HF from October 2019 to September 2020. We sought to increase the percentage of referrals to PC from 6.5% to 20% by May 2021. Methods: PC referral criteria were developed and used to screen all patients admitted to the medical service with HF between October 2020 and May 2021. Patient-centered education on the benefits of PC was delivered initially to medical teams caring for patients who met PC referral criteria and subsequently to all teams. Changes were tested using Plan-Do-Study-Act (PDSA) cycles. Results were analyzed using run charts. Results: Between November 2020 and May 2021, there were 109 HF admissions in patients who were not already followed by PC. Thirty-one (28%) received a new PC consult. The mean age was 83 ± 9.5 years, median B-type natriuretic peptide was 1202 pg/mL, and mean hospital length of stay was 8 ± 5 days. Kansas City Cardiomyopathy Questionnaire-12 was performed on 15 of the 31 patients with a mean score of 60 ± 22. After our intervention, a shift in the percentage of referrals was demonstrated with 6 consecutive data points above the fixed baseline median (Figure). During the index hospitalization, 5 patients died, 4 of whom had a PC consult. Conclusion: Through multiple PDSA cycles, referrals to PC for patients admitted with HF increased from 6.5% to 28%. Patient-centered education was an effective tool to teach medical teams about the benefits of PC. Furthermore, inpatient teams more consistently and independently considered PC for patients with HF, representing a cultural shift. This Quality Improvement model may serve as a paradigm to improve the care of HF patients.
Impact on aerosol generation during upper endoscopy of mouthpiece designed to reduce COVID-19 droplet spread: single-center randomized controlled trial
Authors: I-Hsuan Huang, Pieter Sinonquel, Wout Verbeure, Chelsea Camps, Herman Devriese, Lieselot Holvoet, Bram Verstockt, Hilde Willekens, Hideki Mori, Raf Bisschops, Jan Tack
Journal: Endoscopy (2021)

For nearly 2 years, the COVID-19 pandemic has continued to pose a major public health crisis. COVID-19 spreads through the generation of aerosols and droplets [1]. A growing number of studies have confirmed that esophagogastroduodenoscopy (EGD) is an aerosol-generating procedure [2] [3]. While numerous approaches to decreasing the amount of aerosol have been reported, most of them may reduce patient comfort and entail additional procedure time and personnel. During the pandemic, a droplet-shielding mouthpiece (B1 mouthpiece, MPC-ST; Fujifilm, Tokyo, Japan) was launched. This device is used similarly to the conventional mouthpiece but has a double sponge with slits incorporated into the mouthpiece orifice, and a transparent plastic drape shield ( [Fig. 1]).
Abstract 12088: Coronary Angiography and Revascularization After Out-of-Hospital Cardiac Arrest in Coronary Artery Disease Patients Without ST-segment Elevation
Authors: Giichi Nitta
Journal: Circulation (2021)

Introduction: The emergent coronary angiography and revascularization after out-of-hospital cardiac arrest (OHCA) in coronary artery disease (CAD) patients without ST-segment elevation remains controversial. Methods: There were 2391OHCA patients transferred to 2 hospitals. We included 405 cardiovascular arrest patients, who got return of spontaneous circulation (ROSC) from January 2015 to December 2018. Among them, 110 patients were diagnosed CAD with no ST-segment elevation in electro-cardiogram (51%: multi-vessel disease, 33%: chronic total occlusion). To predict mortality in hospital and neurological outcome at 1-year, we investigated basic patients’ characteristics, pre-hospital information, post-hospital care including coronary angiography (CAG) and revascularization. Results: In the Cox proportional hazards model, emergent coronary angiography (hazards ratio; HR: 0.90, 95%confidence interval (CI) 0.45-1.79, P=0.758) and emergent coronary revascularization (HR: 1.51, 95%CI 0.87-2.61, P=0.142) were not associated to predict the mortality. At 1-year, VF survivor (P=0.004), younger age (P=0.010), without ECMO support (P&lt;0.001), pre-hospital ROSC (P&lt;0.001), and low lactate level on admission (P&lt;0.001) were associated with low mortality. The higher number of coronary vessel disease (P=0.020) such as multi-vessel disease (P=0.019), the coronary lesion of LAD (P=0.043), and larger infarct size (max CK level; P=0.014, max CK-MB level; P&lt;0.001) were associated with high 1-year mortality. Zero-vessel disease (VSA, P=0.007) had lower mortality. Conclusions: Emergent coronary assessment and revascularization were not associated with the prognosis.
Abstract 9751: Combined Cardiomyopathy and Arrhythmia Genetic Testing Identifies Clinical Management Implications and Unexpected Results
Authors: Lisa Dellefave-Castillo, Allison Cirino, Tom E Callis, Ed Esplin, Kathryn Hatchell, Britt Johnson, Ana Morales, Ellen Regalado, Susan Rojahn, Matteo Vatta, Robert Nussbaum, Elizabeth McNally
Journal: Circulation (2021)

Introduction: Genetic testing for heritable cardiomyopathy and arrhythmia syndromes has evolved rapidly and is now recommended by cardiology professional societies to establish a genetic etiology, guide clinical management, and identify at-risk family members through cascade screening. However, the advantages of comprehensive, multi-condition gene panels versus condition-specific gene panels are debated. Objective: To assess the yield and clinical management implications of combined cardiomyopathy and arrhythmia genetic testing in a diverse cohort of patients referred for a suspected inherited cardiomyopathy or arrhythmia using a no-charge, sponsored genetic testing program. Methods: De-identified clinical histories and genetic test results were reviewed from a no-charge cardiomyopathy and arrhythmia genetic testing program. Up to 150 genes associated with cardiomyopathies and arrhythmias were evaluated, and positive findings were compared to provider diagnoses at the time of testing request. Results: In a cohort of 4,782 patients, a positive result (molecular diagnosis) was observed in 961 (20%). Of the positive results, 670/961 (70%) conferred clinical management implications, including genes associated with targeted therapy (6%; 57/961) or increased risk of ventricular arrhythmia (18%; 169/961). Positive results for 11% (75/691) of evaluable patients would have been missed by condition-specific panels based on clinician-provided diagnoses. Conclusions: Combined cardiomyopathy and arrhythmia genetic testing identified clinically-relevant variants for 1 in 5 patients suspected of a cardiomyopathy or arrhythmia. Over two-thirds of positive findings had clinical management implications. Combined disease testing captures &gt;10% of patients who would be missed with condition-specific panels and this greater clinical utility may outweigh the burden of uncertain results.
Targeting up-regulated notch signaling in the CD133+ stem cells within the protected niche of the lymphovascular embolus of inflammatory breast cancer
Authors: Sanford Barsky, Yi Xiao, Yin Ye
Journal: Cancer Research (2007)

721  Inflammatory breast cancer (IBC) is a type of human breast cancer with high metastasis due to the presence of florid lymphovascular tumor emboli. We have recapitulated this phenotype in a human xenograft of IBC(MARY-X). In this xenograft, the tumor emboli (spheroids) are mediated by overexpressed E-cadherin. When the spheroids were disrupted with anti-E-cadherin, the disadhered  underwent apoptosis. When undisrupted, these emboli resist the apoptosis-inducing effects of chemotherapy/radiotherapy. We found specific markers (Stellar, H19, Rex-1, Nestin) known associated with embryonal/neural   to be highly expressed within the MARY-X spheroids. In addition, RT-PCR analyses of MARY-X revealed the expression of OCT4, SOX2, and Nanog, transcriptional determinants essential for the pluripotency and self-renewal of  cells. Most importantly, CD133, a surface marker for human leukemic/gliomic  cells, was also strongly expressed by 60% of the  of the MARY-X spheroids and the lymphovascular emboli of human IBC. Only this CD133+ subpopulation expressed both the  cell transcriptional determinants mentioned previously as well as the capacity for self-renewal and tumorigenicity. Tumorigenicity capacity could be observed within spheroids with as few as 50  or within single  if grown in Matrigel. This CD133+ subpopulation however did not show any fewer genomic alterations by array CGH than the CD133- subpopulation. These findings suggest that MARY-X and therefore IBC contain a high percentage of CD133+ cells,  which seem to be functionally but not hierarchically  cell in nature. Their large number, their tumorigenic potency, their lack of genomic stability and their ability to survive only within the protective niche of the lymphovascular embolus support these conclusions. Because it is uncertain whether selective targeting of E-cadherin on tumor v normal  could successfully and safely disadhere tumor emboli in vivo, we investigated other signaling pathways that we discovered to be up-regulated within the CD133+  of the lymphovascular embolus that might be more amenable to selective targeting. Increased expression of both notch receptors and their ligands were detected. Increased notch signaling was also detected by the upregulation of the notch target genes: HES-1, HES-5. In addition, gamma-secretase inhibitors, inhibitors which block notch signaling pathways caused marked apoptosis of the CD133+ IBC cells, even when they were cytoprotected within their embolic niche. Our results suggest that activation of notch signaling pathways are essential for the maintenance of viable tumor emboli and CD133+ stem cells in particular and that inhibiting these notch pathways with gamma-secretase inhibitors may achieve selective targeting and ultimately a novel and effective therapy for IBC.
Abstract 11219: Impact of Echocardiographic Assessment During First Outpatient Cardiology Consultation on Patient Management
Authors: Raed Aladham, Tasneem Z Naqvi
Journal: Circulation (2021)

Background: Goal directed point of care echo (POCE) has emerged as a quick, bedside tool to assess cardiac structure and function. However, impact of physician performed POCE during cardiac consultation on immediate patient diagnosis, downstream testing and management has not been assessed. Purpose: To study the impact of POCE performed by consulting cardiologist (CC) during initial cardiology consult. Methods: 69 study patients (pts) underwent examination by an expert imaging CC from Jan 2014-May 2016. During 1-hour consultation, medical records were reviewed, medical history and physical exam was performed followed by cardiologist-performed POCE (Philips CX50). We included a matched control group of 65 pts seen by 3 different CCs during the same time period who underwent standard echo (Secho) up to 3 months after the initial visit. Results: Baseline characteristics were comparable between the two groups for age (mean of 62 ) , cardiac risk factors, and referral diagnoses. POCE findings and Secho (mean delay of 17.2 days after visit) are shown in Table1 and diagnostic tests ordered following initial visit in both groups in Figure 1. POCE had greater yield of echo abnormalities and led to less referral for noninvasive stress testing, more cardiovascular medication changes (15.3 vs 5.7% pts) and more advanced cardiac testing (21 vs 9% pts) compared to the control group after the initial visit. Conclusion: Focused echo at time of consultation leads to more medication adjustments, less referral for noninvasive stress testing, earlier referral for advanced cardiac diagnostic imaging and shortens time to advanced diagnostic workup by about two weeks.
Immunogenicity trends 1 and 3 months after second BNT162B2 vaccination among healthcare workers in Israel
Authors: Yael Shachor-Meyouhas, Khetam Hussein, Halima Dabaja-Younis, Moran Szwarcwort-Cohen, Ronit Almog, Avi Weissman, Michal Mekel, Gila Hyams, Nethanel A. Horowitz, Vardit Gepstein, Itamar Netzer, Hagar Cohen Saban, Neta Petersiel, Jalal Tarabeia, Michael Halberthal
Journal: Clinical Microbiology and Infection (2021)
Acute Myeloid Leukemia in the Context of Previous History of Cancer with or without Exposure to Chemotherapy or Radiotherapy
Authors: Kebede H. Begna, Mithun V. Shah, Naseema Gangat, Hassan B. Alkhateeb, Mrinal M. Patnaik, Aref Al-Kali, Michelle A. Elliot, William J Hogan, Mark R. Litzow, C. Christopher Hook, Abhishek A. Mangaonkar, Rong He, Dong Chen, Animesh Pardanani, Rhett P. Ketterling, Ayalew Tefferi
Journal: Blood (2021)
Abstract 9857: Epicardial Hdac3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway
Authors: Jihyun Jang, Deqiang Li
Journal: Circulation (2021)

Growth cues from epicardium-derived cells (EPDCs) such as Insulin growth factors (IGFs) and Fibroblast Growth Factors (FGFs) are required for compact myocardial growth, although it is unclear whether/how their expression is regulated by chromatin modifications during this process. To understand the potential function of Histone deacetylase 3 (Hdac3) in the developing epicardium, we conditionally inactivated Hdac3 in the EPDCs. Strikingly, deletion of Hdac3 in the epicardium led to ventricular myocardial wall hypoplasia along with the reduction of EPDCs. To identify disrupted growth signals sending from epicardium to myocardium, we deleted Hdac3 in cultured mouse epicardial cells (MECs) by CRISPR/CAS9 and performed RNA Seq analyses. We found that IGF2 and FGF9 were significantly down regulated in Hdac3 knockout (KO) MECs, which can be rescued by re-expression of intact Hdac3 but not by catalytically dead Hdac3. Importantly, the proliferation of cultured primary embryonic cardiomyocytes was significantly decreased when treated with Hdac3 KO MEC supernatant as compared to those treated with control MEC supernatant, and this proliferation decrease was rescued by supplementation of IGF2 or FGF9. Next, we sought to understand how Hdac3 regulates the expression of IGF2 or FGF9. Interestingly, we found that miR-322/503 was significantly upregulated in Hdac3 KO MECs and Hdac3 epicardial KO hearts. Overexpression of miR-322/503 repressed the expression of IGF2 and FGF9, while knockdown of miR-322/503 restored the expression of IGF2 and FGF9 in Hdac3 KO MECs. Altogether, our findings suggest that Hdac3 in the developing epicardium promotes compact myocardial growth by stimulating IGF2 expression through repressing miR-322/503. Our findings shed light on the potential novel mechanisms of congenital heart defects, and new strategies for myocardial regeneration.
Abstract 13767: Reaching the LDL-Cholesterol Target Recommended by the Guidelines: Be Ambitious to Get the Maximum Benefit
Authors: Matteo Casula, Ivan Taietti, Marco Galazzi, Iris Zeqaj, Federico Fortuni, Stefano Cornara, Alberto Somaschini, Sergio Leonardi, Rita Camporotondo, Rossana Totaro, Marco Ferlini, Massimiliano Gnecchi
Journal: Circulation (2021)

Introduction: There is no agreement among international guidelines (GL) on the recommended therapeutic target for LDL cholesterol in secondary prevention (SP). Hypothesis: The aim of this study was to determine the risk of major adverse cardiovascular events (MACE) during follow-up in a real-world SP population according to the achievement of a purely numerical threshold (i.e. LDL&lt;1.8mmol/L [Canadian 2021 GL], group A) or a target that also considers a relative reduction in LDL levels (i.e. LDL reduced ≥50% from baseline and &lt;1.8mmol/L [AHA/ACC 2018 GL] or &lt;1.4 mmol/L [ESC 2019 GL], group B). Methods: We conducted a retrospective analysis of a monocentric observational registry prospectively enrolling patients admitted for STEMI between 2011 and 2019. The combined endpoint of MACE included all-cause death, non-fatal MI, non-fatal stroke, and unplanned revascularization. The lowest LDL value collected between 1 and 12 months after the index event was used to define the achievement of the target. We conducted a Kaplan-Meier analysis comparing patients who achieved different GL-recommended targets. Results: A total of 1199 patients (23% female) were included. Median age was 63 (54-72) years, 56% had hypertension, 17% diabetes, and 38% were smoker. Baseline LDL was 3.2 (2.5-3.8) mmol/L; 83% of patients were treated with statin therapy alone, and 17% with the addition of ezetimibe. Median follow-up was 53 (32-70) months. The Canadian, AHA/ACC and ESC targets were achieved in 842 (70%), 506 (42%) and 308 (26%) patients respectively; MACE-free analysis based on the target achieved is presented in FigA. The net incidence of MACE was 29% in group A vs 15% in group B (HR 1.97; 95%CI 1.36-2.85; P log-rank=0.0003; NNT=7; FigB). Conclusions: Our data from a real-world cohort of secondary prevention patients emphasize the importance of achieving a guideline-recommended target that also considers a relative reduction in LDL levels (i.e. LDL ≤50% from baseline) in order to reduce MACE.
Outcomes with "Off the Shelf" Allogeneic CD19 Chimeric Antigen Receptor T Cell Therapy for Hematological Malignancies: A Systematic Review and Meta-Analysis
Authors: Muhammad Umair Mushtaq, Moazzam Shahzad, Ali Hussain, Amna Y Shah, Raheel S Siddiqui, Muhammad Salman Faisal, Iqra Anwar, Sibgha Gull Chaudhary, Ghulam Rehman Mohyuddin, Ramesh Balusu, Aung M Tun, Rajat Bansal, Haitham Abdelhakim, Marc Hoffmann, Anurag K. Singh, Leyla Shune, Sunil Abhyankar, Joseph P. McGuirk, Nausheen Ahmed
Journal: Blood (2021)
Intestinal microbial communities and<i>Holdemanella</i>isolated from HIV+/− men who have sex with men increase frequencies of lamina propria CCR5<sup>+</sup>CD4<sup>+</sup>T cells
Authors: Eiko Yamada, Casey G. Martin, Nancy Moreno-Huizar, Jennifer Fouquier, C. Preston Neff, Sara L. Coleman, Jennifer M. Schneider, Jonathan Huber, Nichole M. Nusbacher, Martin McCarter, Thomas B. Campbell, Catherine A. Lozupone, Brent E. Palmer
Journal: Gut Microbes (2021)

Men who have sex with men (MSM), regardless of HIV infection status, have an intestinal microbiome that is compositionally distinct from men who have sex with women (MSW) and women. We recently showed HIV-negative MSM have elevated levels of intestinal CD4+ T cells expressing CCR5, a critical co-receptor for HIV. Whether elevated expression of CCR5 is driven by the altered gut microbiome composition in MSM has not been explored. Here we used in vitro stimulation of gut Lamina Propria Mononuclear Cells (LPMCs) with whole intact microbial cells isolated from stool to demonstrate that fecal bacterial communities (FBCs) from HIV-positive/negative MSM induced higher frequencies of CCR5+ CD4+ T cells compared to FBCs from HIV-negative MSW and women. To identify potential microbial drivers, we related the frequency of CCR5+ CD4+ T cells to the abundance of individual microbial taxa in rectal biopsy of HIV-positive/negative MSM and controls, and Holdemanella biformis was strongly associated with increased frequency of CCR5+ CD4+ T cells. We used in vitro stimulation of gut LPMCs with the type strain of H. biformis, a second strain of H. biformis and an isolate of the closely related Holdemanella porci , cultured from either a HIV-positive or a HIV-negative MSM stool. H. porci elevated the frequency of both CCR5+ CD4+ T cells and the ratio of TNF-α/IL-10 Genomic comparisons of the 3 Holdemanella isolates revealed unique cell wall and capsular components, which may be responsible for their differences in immunogenicity. These findings describe a novel mechanism potentially linking intestinal dysbiosis in MSM to HIV transmission and mucosal pathogenesis.
EXTH-61. MODULATION OF THE IL-27 RECEPTOR SIGNALING PATHWAY IN GLIOBLASTOMA AND ONCOLYTIC VIROTHERAPY
Authors: Eleni Panagioti, Michal Nowicki, William Goins, Jorge Jimenez Macias, Julia Escobar, Mykola Zdioruk, Shikha Saini, Keith Ligon, Ana Carrizosa Anderson, Vijay Kumar Kuchroo, Sean Lawler, E Antonio Chiocca
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with median overall survival of 14-16 months. Glioblastoma progression involves multiple immunosuppressive pathways hindering the success of cancer immunotherapy. Oncolytic virotherapy is a promising approach to reprogram the glioblastoma microenvironment and restore anti-tumor immunity. Interleukin (IL)-27 receptor signaling pathway regulates development of effector T cells, IL-10 producing T regulatory type 1 (Tr1) cells and induction of co-inhibitory receptors associated with T cell exhaustion in cancer. In this study, we sought to tackle local and systemic GBM-induced immunosuppression using the novel rQNestin34.5v2 oncolytic herpes simplex virus type-1 (HSV-1), engineered to selectively replicate in glioma cells together with genetic disruptions of the IL-27 receptor signaling pathway. The antitumor activity of HSV-1 rQNestin34.5v2 was evaluated in IL-27ra-/- and wild-type C57BL/6 mice harboring orthotopic CT-2A and GL261 glioblastoma and in athymic nude mice harboring orthotopic patient derived glioblastoma xenografts (PDXs) selected from patients that had been treated in a clinical trial of intratumoral administration of HSV-1 rQNestin34.5v2 (ClinicalTrials.gov: NCT03152318). HSV-1 rQNestin34.5v2 exhibited superior capacity to infect glioma cells in vitro triggering release of proinflammatory cytokines and inducing immunogenic cell death in infected cells. Immune phenotyping of GL261 and CT-2A gliomas revealed astrocytes and microglia express the highest levels of IL-27R. Lack of IL-27R signaling decreased expression of the co-inhibitory receptors PD-1 and Tim-3 on circulating CD4+ T cells suggesting altered CD4+ T cell responses. In the tumor microenvironment, lack of IL-27R signaling decreased immune suppression as evidenced by reduced interleukin (IL)-10 secretion by glioma cells. Despite positive functional modifications on CD4+ T cells, global lack of IL-27R signaling promoted tumor growth accompanied by increased circulating myeloid derived suppressor cells (MDSCs) in the GL261 model. Experiments to address the immunoregulatory role of IL-27R signaling during HSV-1 rQNestin34.5v2 virotherapy-induced glioma tissue destruction are ongoing.
EPID-27. GEOGRAPHIC BURDEN OF CNS TUMORS AND DENSITY OF NEURO-ONCOLOGISTS IN THE UNITED STATES
Authors: Timothy Gregory, Jerome Graber
Journal: Neuro-Oncology (2021)

Abstract CNS cancer care relies heavily on exam and imaging interpretation skills distinctive to a neurology-trained oncologist, and access to this subspecialty is increasingly more essential as targeted molecular therapies evolve. We sought to explore the supply of neuro-oncologists in terms of geographic CNS tumor incidence. Using the UCNS online directory, we generated a heat map representing the location (set to 75-mile radius) and density of active neuro-oncologists. We overlaid this data upon yearly incidence of CNS tumors per neuro-oncologist for each state using most recent CBTRUS data. We highlight the significant distance Americans outside of urban areas must travel for care and that isolation from academic centers and exclusion from clinical trials are substantial barriers to cancer care for a significant proportion of the population. Telemedicine may in part improve patient access to care and clinical trial participation, but significant state-to-state legal variability for providing telehealth services across state lines remains a national challenge. Short-term strategies for equitably meeting this subspecialty need may require policy changes that optimize employment of telemedicine, and long-term must ensure a robust fellowship pipeline with thoughtful incentivization and allocation of resources.