tbuckley/cabot-search huggingface dataset:
TAMI-58. TARGETING GLIOBLASTOMA BY ACTIVATING VIRAL SPECIFIC TISSUE-RESIDENT MEMORY T CELLS
Authors: Jianfang Ning, Noah Gavil, Shaoping Wu, Jun Ma, Ming Li, Florina Grigore, Sanjay Dhawan, David Masopust, Clark Chen, Pamela Rosato
Journal: Neuro-Oncology (2021)

Abstract Immunotherapy with the success of checkpoint blockade brings hope for cancer treatment with enduring or complete responses in various types of advanced malignancies, however, it has not benefited a number of so called “cold tumors”, such as glioblastoma multiforme (GBM), the most common and aggressive adult brain cancer. GBM is invariably lethal with a median survival of less than 15 months and characterized by a highly immunosuppressive tumor microenvironment, which desires new means of GBM immune-reactivation. Tissue-resident memory CD8+ T (TRM) cells are non-recirculating memory T cell subpopulation that resides permanently in peripheral tissues. TRM cells provide long-lived protective immunity against not only local pathogen infection but also tumor development through immediate effector function and recruitment of circulating immune cells upon antigen re-exposure. In this study, we found that memory T cells specific to some common human viruses that have infected almost everybody exist in clinical GBM specimens and can be activated by viral peptides, which are MHC I restricted CD8+ T cell epitopes derived from those viruses. In orthotopic GBM immunocompetent mouse models, we detected abundant virus specific TRM cells in the tumor microenvironment of GBMs intracranially established in mice that were previously exposed to the virus. Excitingly, intratumoral injection of viral peptides stimulated the reactivation of TRM cells, indicated by secretion of immuno-stimulatory cytokines, and demonstrated significant anti-tumor efficacy. This study provides proof of principle for TRM cell-based GBM therapy, which is a novel therapeutic paradigm with the translational potential for this deadly malignancy.
Is nature truly healing itself? Spontaneous remissions in Paroxysmal Nocturnal Hemoglobinuria
Authors: Carmelo Gurnari, Simona Pagliuca, Tariq Kewan, Waled Bahaj, Minako Mori, Bhumika J. Patel, Valeria Visconte, Jaroslaw P. Maciejewski
Journal: Blood Cancer Journal (2021)
Abstract 11665: Does the Benefit of Secondary Prevention Implantable Cardioverter-Defibrillators Vary Based on the Estimated Proportional Risk of Sudden Death?
Authors: Molly E Kelly, Kenneth C Bilchick, Todd F Dardas, Ramin Shadman, Neal A Chatterjee, Wayne C Levy
Journal: Circulation (2021)

Introduction: The Seattle Proportional Risk Model (SPRM) is a validated model developed in systolic heart failure patients without implantable cardioverter-defibrillators (ICDs) to estimate the proportion of all-cause mortality (ACM) due to sudden death. This study aims to ascertain if SPRM has utility in risk stratification for secondary prevention ICD. Methods: The AVID (Antiarrhythmics Versus Implantable Defibrillators) trial was a multicenter, randomized clinical trial in which 1,016 patients presenting with ventricular fibrillation or sustained, symptomatic ventricular tachycardia were randomized to ICD or antiarrhythmic (AA) drug therapy. Using routine clinical variables, we applied the SPRM to patient-level data (n=995 with complete data) and assessed if the ICD benefit for ACM varied with SPRM-predicted probability of sudden death. Results: SPRM was predictive of sudden death vs. non-sudden death in patients without an ICD (logistic regression p=0.005). The ICD hazard ratio for ACM was 0.59. ICD survival benefit varied with SPRM for ACM (p=0.013) with benefit (ICD HR≤0.80) seen in patients with SPRM&gt;40%. ICD benefit trended higher in patients with a history of heart failure (HF) vs no HF (HR=0.52 vs. 0.81, interaction p=0.13) (Figure 1). In comparison to the AA group, patients with either HF or SPRM&gt;51% (median) had a meaningful ICD benefit (HR=0.60, p=0.017), and patients with both HF and SPRM&gt;51% had the greatest ICD benefit (HR=0.38, p&lt;0.001). There was no ICD benefit if no HF and SPRM&lt;51% (HR=1.17). Conclusions: In a population of patients with VF or sustained VT, secondary prevention ICDs decreased ACM by 41%. ICD survival benefit varied with SPRM-predicted proportion of sudden death, and trended higher in patients with HF. SPRM may therefore provide a useful tool for risk stratifying patients for secondary prevention ICD. Figure 1: Survival benefit for ICD therapy varies with SPRM-estimated proportion of sudden death, and HF versus no HF.
Abstract 6905: Implementing, Launching and Sustaining a Quality Improvement Initiative in the Era of COVID-19: Challenges and Successes
Authors: Kun Xiang, David McManus, Christina Catalano, Sue Ash, Patrick Fry, Jose Morales, kyeesha Becoats, Sebastian Mikulic, Andres Martinez, Jose Rivas, Anne Marie Smith, Mary Martin Lowe, Almaz Araia, Alok Kapoor, John N Catanzaro
Journal: Circulation (2021)

Introduction: Only 60% of atrial fibrillation (AF) patients with elevated stroke risk receive anticoagulation (AC). Closing this gap in AC use is particularly challenging in the face of the COVID-19 pandemic. Electronic health record (EHR) alerts integrated into in-person and telehealth visits have the potential to close the gap. Hypothesis: A triad approach consisting of interventions at the practice provider at patient level could improve anticoagulation rates in patients with atrial fibrillation. Methods: In collaboration with the Heart Rhythm Society Quality Improvement Committee and UMass, University of Florida (UFL) Jacksonville launched a 2020 quality improvement (QI) intervention, including several Plan-Do-Study-Act (PDSA) cycles, centered around an outpatient, electronic health record (EHR) alert linked to an order set for AC meds, labs, and specialty referrals. The alert fired when cardiologists or primary care physicians saw AF patients in clinic with a CHA 2 DS 2 -VASc score of ≥2 who were not on AC. Due to COVID-19, several of the PDSA interventions required adjustments due to redeployment of information technology staff mobilized to generate COVID-19 reports, a pivot for clinicians and patients to telehealth visits, and a change in clinician and patient priorities from routine cardiovascular/preventive care to COVID-19 diagnosis and prevention. To assess intervention effectiveness, the change in AC use as a function of time was measured using a weighted least squares linear regression. Results: At time of launch, 2357 of 3555 eligible patients (56.3%) were on AC. At study end, six months later, the percentage of patients on AC increased by 1.5% to 57.8 %. Based on the population of untreated patients at UFL and the stroke rate for untreated patients (available from large registry data), and assuming absence of any competing/secular trend to explain the growth in AC use, we calculated that a 1.5% increase in the AC treatment percentage could result in the prevention of 1.5 strokes over one year. Conclusion: We demonstrated that an EHR alert can raise the rate of AC use in patients with AF after several rounds of PDSAs. In future efforts, we plan to reassess the AC percentage in our population and confirm the sustainability of our QI efforts as attention focuses back from the pandemic to routine cardiovascular/ preventive care.
EPID-24. TRANSCRIPT: A cenTRAl NERVOUS SYSTEM CANCER CLINICAL tRIals PostmorTem
Authors: Yeonju Kim, Terri Armstrong, Mark Gilbert, Orieta Celiku
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Despite the growing number of neuro-oncology clinical trials, there have been limited advances in the treatment of malignant primary central nervous system tumors. We surveyed the landscape of past, ongoing, and planned trials to assess trends in their interventions, outcomes, and design considerations to guide future studies. METHODS Data on interventional trials on ClinicalTrials.gov were accessed programmatically using AACT and R. Neuro-oncology trials were isolated using primary malignant brain tumor classification terms. Instrument names from PROQOLID were used to identify clinical outcome assessment (COA) use. Linear regression was used to assess chronological trends; power analyses utilized CBTRUS survival rates among trials investigating overall survival. RESULTS We identified 3039 interventional brain tumor trials that started between 1966 and 2025. Trials were most frequently phase II (43%), completed (40%), non-blinded (92%), single-group assignment (65%), non-randomized (51%) studies targeting glioblastoma (45%). Planned outcomes were reported by 93% of trials; this included adverse event or toxicity (54%), overall/x-year survival (44%), progression free survival (43%), maximum tolerated dose (16%), and objective response rate (14%). Evaluating the anticipated and actual trial enrollment, we estimate that only 10% and 8% of trial arms, respectively, were sufficiently powered to assess overall survival endpoints. 21% of trials mentioned the use of a COA (first trial initiated in 1992), majority of which were patient-reported outcomes. Among these, 25% and 58% reported COA as a primary or secondary outcome, respectively. The rate of COA use increased linearly over time at 1.1%/year but remained less than 5 trials per year until 2003. Ongoing work is investigating treatment mechanisms of actions and evidence of preclinical efficacy among brain tumor studies. CONCLUSIONS Low randomization rates and underpowered trial design may impede interpretability of efficacy. Increasing trends in COA use suggests cumulative influence of advocacy efforts to holistically evaluate net clinical benefit of interventions.
Abstract 13609: Impact of Frailty on Hospital-Related Outcomes of Elective Left Atrial Appendage Closure
Authors: Weijia Li, Saul Rios, Lingling Wu, Chengyue Jin
Journal: Circulation (2021)

Introduction: Atrial fibrillation as the most common arrhythmia worldwide results in a significantly elevated risk of cardioembolic stroke. Left atrial appendage (LAA) closure has been advocated and supported by randomized clinical trials as an alternative treatment in patients with atrial fibrillation who have contraindications for anticoagulation. The safety of this procedure in patients who are considered frail remains unknown since they have been underrepresented in most clinical studies. Our study aims to investigate the impact of frailty on hospital-related outcomes in patients undergoing elective LAA closure. Methods: We reviewed the National Inpatient Sample database from January 2016 to December 2017 to identify patients that underwent elective percutaneous LAA closure using the ICD-10 code 02L73DK for the procedure. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. An individual is considered frail if they present &gt;=1 diagnosis within the indicator. The outcomes include in-hospital mortality, hemorrhage requiring blood transfusion, respiratory failure, sepsis, length of stay, and total hospitalization cost. Multivariate logistic or linear regression was adopted to determine the impact of frailty on the outcomes while reducing the effect of possible confounding baseline characteristics. Results: From the period of January 2016 to December 2017, a total of 14795 patients underwent elective LAA closure. Of those patients, 830 were determined to meet the criteria for frailty, while 13965 were considered non-frail. The frail group is older than the non-frail group with a mean age of 78.77 years old than 75.53 years old. Frailty was associated with an increased risk of hemorrhage requiring transfusion (odds ratio 2.82, p=0.030) and a longer length of stay (2.10 vs 1.30 days, p=0.003). The frail group appears to have higher hospitalization costs, but the result was not statistically significant ($122668.2 vs $114295.3, p=0.091). Conclusions: The presence of frailty was associated with an increased risk of hemorrhage requiring transfusion and a longer length of hospital stay after elective left atrial appendage closure.
Estimating averted COVID-19 cases, hospitalisations, intensive care unit admissions and deaths by COVID-19 vaccination, Italy, January−September 2021
Authors: Chiara Sacco, Alberto Mateo-Urdiales, Daniele Petrone, Matteo Spuri, Massimo Fabiani, Maria Fenicia Vescio, Marco Bressi, Flavia Riccardo, Martina Del Manso, Antonino Bella, Patrizio Pezzotti
Journal: Eurosurveillance (2021)

We assessed the impact of COVID-19 vaccination in Italy, by estimating numbers of averted COVID-19 cases, hospitalisations, ICU admissions and deaths between January and September 2021, by age group and geographical macro areas. Timing and speed of vaccination programme implementation varied slightly between geographical areas, particularly for older adults. We estimated that 445,193 (17% of expected; range: 331,059-616,054) cases, 79,152 (32%; range: 53,209-148,756) hospitalisations, 9,839 ICU admissions (29%; range: 6,434-16,276) and 22,067 (38%; range: 13,571-48,026) deaths were prevented by vaccination.
Abstract 11060: Clinical Impact of the Barthel Index/Blood Urea Nitrogen Ratio to Predict the Post-Discharge Prognosis in Patients with Acute Decompensated Heart Failure
Authors: Koichi Ohashi, Daisuke Abe, Riki Nagatomo, Taichi Kato, Mikiko Okouchi, Takunori Aoyama, Hitoshi Hirano, Akira Takayama, Akira Kimata, Ai Hattori, Norihiro Kuroki, Kou Suzuki
Journal: Circulation (2021)

Purpose: Several clinical models and scales have been reported to predict prognosis of patients who have hospitalized due to acute decompensated heart failure (ADHF). It is known that high blood urea nitrogen (BUN) levels and low activities of daily living are associated with a worse prognosis in patients with HF. Barthel Index (BI) is an ordinal scale used to measure performance in activities of daily living and functional independence in the domains of personal care and mobility. The aim of this study was to investigate the association between BI/BUN ratio and the incidence of clinical outcomes in patients with ADHF. Methods: A cohort of 76 patients admitted to our institution from August 2019 to December 2019 due to ADHF was enrolled. We investigated the characteristics of these patients and BI at their discharge. Clinical outcome was major adverse cardiovascular event (MACE) which include cardiovascular death and re-hospitalization for worsening HF. We performed ROC analysis for MACE. Results: The patients had a mean age of 78.0 years and 61.8% were male. Incidence of MACE was 51.3% in entire patients. We explored the association between BI/BUN ratio and post-discharge MACE. Area under the curve of BI/BUN ratio for MACE was 0.66(95% CI: 0.54-0.78) and the cut off value was 2.01 (specificity 0.784, sensitivity 0.538). We divided patients into 2 groups according to cut off value; high BI/BUN (&gt;2: n=48) and low BI/BUN (&lt;2: n=28). During the follow up periods (193±118 days), incidence of MACE was significantly higher in low BI/BUN group than in high BI/BUN group (71.4% vs. 39.6%, p=0.007). Kaplan-Meier curve of MACE showed high BI/BUN was better outcome compared with low BI/BUN (p=0.002, between log-rank test). After adjustment of multiple cofounders, BI/BUN ratio was a negative independent predictor for MACE (OR: 0.26 per increase, 95% confidence interval: 0.13-0.54, p=0.0003). Conclusion: We suggest that low BI/BUN ratio predicts poor prognosis in patients admitted due to ADHF.
Drug hypersensitivity in SARS-coV-2 patients with skin lesions during the first wave of infection
Authors: I. P. Allegue, V. C. Guzman, R. C. Hernandez, A. C. Herrero, L. P. Quintanilla, D. F. Nieto, M. F. Guarino, D. O. Quijano, C. Moreno, A. D. Martin, E. S. Solares, D. G. De Olano, B. D. Caballer
Journal: Allergy (2021)
Better modelling of infectious diseases: lessons from covid-19 in China
Authors: Yongyue Wei, Feng Sha, Yang Zhao, Qingwu Jiang, Yuantao Hao, Feng Chen
Journal: BMJ (2021)

Better modelling of infectious diseases: lessons from covid-19 in ChinaMore timely, accurate, and relevant data and methodological innovation could exploit the full power of modelling, argue
Abstract 13454: Cardiac Abnormalities in a Large Student Athletes Screening Cohort in Central Texas
Authors: Yousuf Ahmed, Matthew Seghers, Michelle Garcia, Arnold L Fenrich, George Rodgers, Silvana M Molossi
Journal: Circulation (2021)

Introduction: Sudden cardiac death (SCD) in the young is a rare but devastating event. Pre-participation evaluation is required prior to competitive sports. The Texas Adolescent Athlete Heart Screening Registry (TAAHSR) performs screening events including history, ECG and limited echocardiogram (ECHO). Hypothesis: Cardiac abnormalities are identified in athlete screening and challenges exist in long-term follow up. Methods: The TAAHSR database of 4309 participants between 2013-2020 was analyzed and follow up data obtained from phone and electronic medical records. Screening results were classified as: I - no abnormality (abnl) identified, II - abnl identified and further evaluation but no activity restriction recommended, level III - abnl identified and further evaluation with activity restriction recommended if concern for SCD. Results: Of 4309 participants, 218 (5%) screened positive on either ECG, ECHO, or both. ECG abnl were seen in 117/4309 (2.7%) level II and 23/4309 level III (0.5%). ECHO abnl were seen in 73/4309 (1.7%) level II and 13/4307 (0.3%) level III. The most frequent abnl in 218 positive screenings included: ECG - right ventricular hypertrophy (27, 12%), right bundle branch block (26, 12%), T-wave abnormalities (23, 10%), left ventricular hypertrophy (22, 10%), left axis deviation (17, 8%), Wolff-Parkinson-White (8, 4%); ECHO - bicuspid aortic valve (15, 7%), mitral valve prolapse (9, 4%), increased left ventricular trabeculations (9, 4%). The most frequent positive history in the cohort (218) was family history of heart disease (56, 25%), racing or skipped beats (30, 14%), chest pain after exercise (28, 13%), family history of SCD before age 50 (21, 10%). Follow up data was obtained, to date, in 130/218 (60%) positive screening participants and 72/130 (55%) had the suspected diagnosis confirmed. Of 130, 42 (32%) were reached and are alive at median follow up of 5.3 years. Conclusions: Our data shows 3.2% ECG and 2% ECHO positive screening for suspected cardiovascular abnl. Screening results may improve with better utilization of ECG criteria in athletes and lower referral based on ECHO findings that may represent normal pattern in certain populations. Follow up remains a challenge to determine long term outcomes of athlete screening.
Abstract 13309: Differences in Clinical Characteristics and Hospitalizations Between Midrange, Reduced and Preserved Heart Failure
Authors: Nathan Wheeler, Naga Dharmavaram, Furqan Rajput, Timothy Hess, Aurangzeb Baber, Farhan Raza, Ravi Dhingra
Journal: Circulation (2021)

Introduction: Distinct pathophysiologic differences exist among heart failure (HF) patients depending on baseline left ventricular ejection fraction (LVEF) and degree of LVEF recovery to medical therapy; however, differences in clinical outcomes among these patients remain unclear. Hypothesis: We hypothesized that patients with HF and mid-range EF (HFmrEF) would have lower all cause and HF hospitalizations compared to HFpEF and HFrEF patients. Methods: We identified 9,428 patients between 2009-2018 with ICD diagnosis of HF with a baseline and 1-year follow-up echocardiogram. We created 9 subgroups based on initial and follow-up ejection fraction (LVEF defined as preserved &gt;50%; midrange 40-50% and reduced &lt;40%). All-cause and HF hospitalizations crude incidence rates and length of stay were calculated as per patient follow-up year. Results: A total of 424 HFmrEF patients who maintained mid-range ejection fraction at follow-up were included in our analysis. HFmrEF patients were less likely to have pulmonary hypertension and more likely to have ischemic cardiomyopathy, coronary artery disease, hyperlipidemia compared to HFrEF and HFpEF (P &lt;0.001). There were 47832 total and 18594 HF hospitalizations with a mean follow-up time of 3.89 years. Patients with HFmrEF who stay mid-range had the lowest number of total (0.97 per follow-up year, P&lt;0.001) and HF hospitalizations (0.43, P&lt;0.001) when compared to all other groups. HFmrEF who stay mid-range also had the lowest length of stay during both total and HF hospitalizations (2.85 and 1.91, P&lt;0.001). Conclusions: Patients who have mid-range ejection fraction at diagnosis and at follow-up had lower all cause and HF hospitalizations and shorter length of stay when compared to HFrEF, recovered EF, and HFpEF patients. Further research is needed to determine the proper management of this group.
Abstract 14424: Association of Beta-1 Adrenergic Receptor Autoantibodies With Heart Failure Risk in Systemic Sclerosis
Authors: Alexia A Zagouras, Thanat Chaikijurajai, Rommel Morales, Soumya Chatterjee, Wai Hong W Tang
Journal: Circulation (2021)

Introduction: Systemic sclerosis (SSc) is associated with the greatest independent risk of heart failure (HF) among systemic autoimmune diseases. Cardiac involvement in SSc also includes cardiomyopathy (CM), diastolic dysfunction (DD), and arrhythmias. Diffuse cutaneous SSc (dcSSc) is associated with greater cardiac risk than limited cutaneous SSc (lcSSc). Prior studies have examined the pathogenic roles of anti-beta-1 adrenergic receptor autoantibodies (β1AR-AAbs) and the protective role of the IgG3 subclass of β1AR-AAbs in HF. We aimed to investigate the associations between β1AR-AAb IgG/IgG3 seropositivity and disease phenotype in an SSc cohort. Methods: Serum samples were collected with informed consent from SSc patients with and without cardiac involvement, as approved by the Cleveland Clinic Institutional Review Board. Enzyme-linked immunosorbent assays were performed to investigate the presence of circulating IgG and IgG3 subtype β1AR-AAbs. Average optical density (OD) was compared between SSc and healthy control samples to establish seropositivity at the 2x control threshold level. Proportions of patients positive for β1AR-AAbs in different groups were compared using Fisher’s exact test. Results: Samples were collected from 36 SSc patients, of whom 20 (56%) had lcSSc and 15 (42%) had dcSSc. Cardiac involvement included HF, CM, DD, and arrhythmia, at least one of which was documented in 9 patients (25%). Of the total SSc cohort, 11 (31%) and 7 (19%) were positive for anti-β1AR IgG and IgG3 respectively. Between SSc patients with and without cardiac involvement, there was no significant difference in IgG or IgG3 positivity. There was a significant increase in IgG3 positivity in the lcSSc group compared to the dcSSc group at the 2x control threshold (p = 0.0125). Conclusions: High anti-β1AR IgG3 positivity is associated with less severe disease category (lcSSc vs. dcSSc) in our SSc cohort, supporting prior evidence of the protective role of the IgG3 subtype. A larger sample size will allow for further investigation of the associations between IgG/IgG3 β1AR-AAbs and cardiac involvement in SSc.