tbuckley/cabot-search huggingface dataset:
Assessing the Role of BCOR/BCORL1 and Other Historically Low-Frequency Somatic Mutations in Myelodysplastic Syndromes
Authors: Taha Alrifai, Natasha Edwin, Dale L. Bixby, Adam John Hockenberry, Emmanuel Okeke, Brett Mahon, Duane C Hassane, Sari Heitner Enschede, Melissa Larson, Jamile M. Shammo
Journal: Blood (2021)
Abstract 11161: Comparison of Percutaneous Mitral Valve Repair in Patients with Normal vs Severely Reduced Ejection Fraction
Authors: Konstantinos Voudris, Caleb Chiang, Clifford J Kavinsky, Hussam Suradi
Journal: Circulation (2021)

Introduction: Percutaneous mitral valve repair (PMVR) has been established as a suitable alternative to mitral valve surgery in patients with severe mitral regurgitation (MR). Patients with severely decreased ejection fraction (EF≤ 30%) constitute a higher risk group for adverse outcomes and peri-operative mortality. Hypothesis: We sought to examine the efficacy and safety of MitraClip implantation in severe heart failure patients in comparison to patients with preserved LV function. Methods: Single-center, retrospective study of patients undergoing PMVR between January 2015 and December 2020. All patients were followed up for 30 days. Baseline and procedural characteristics as well as short term outcomes of all-cause mortality, heart failure hospitalizations, stroke, new atrial fibrillation, new pacemaker placement, and improvement in MR severity ≥2 grades and NYHA class were assessed. Results: Among 86 patients undergoing PMVR, 26 had severely decreased EF. Patients with severely decreased EF were younger and more likely to have diabetes and mixed pathology MR. Additionally they received guideline directed medical therapy at higher rates. Characteristics of the population are shown in Table 1. At 30 days, no significant difference was observed between the two groups in regards to all-cause mortality, HF hospitalization, stroke, new atrial fibrillation, new pacemaker placement, and improvement in MR severity ≥2 grades and NYHA class. Conclusions: PMVR with the MitraClip system is feasible and a safe option for patients with MR and severely reduced EF.
Abstract 11099: <i>Treml4</i> , Snps and Regulatory Mirnas in the Diagnosis of Subclinical Atherosclerosis
Authors: VICTOR HUGO REZENDE R DUARTE, KARLA SIMONE C COSTA DE SOUZA, Mariana Lopes, Renata C Freitas, Adriana Bertolami, Rosario Hirata, Mario Hirata, Andre D Luchessi, Vivian N Silbiger
Journal: Circulation (2021)

Considering the multifactorial nature of the development of coronary artery calcificatioN (CAD), and the difficulty in making its early diagnosis, this study sought to investigate the role of the TREML4 in the development of atherosclerotic lesions by genotyping of two main variants associated with this gene (rs2803495 and rs2803496), mRNA expression and identification of its regulatory miRNAs. 329 patients with Subclinical atherosclerosis (AS) were recruited. The results with AS patients stratified according to the Duke score demonstrated an association of the Duke score with increased expression of mRNA of the TREML4 in peripheral blood leukocytes (OR. = 3.173, 95% CI = 1.29-7, 78, p = 0.012). Furthermore, genotyping revealed that the SNP genotype combination rs2803495 (AG + GG) (OR = 9,007, 95% CI = 4.1-19.8, p &lt;0.001) and rs2803496 (CT + CC) ( OR = 11.1, 95% CI = 4.8-25.4, p = 0.011), favor the expression of TREML4 mRNA. Patients with AS and carriers of the SNP G alleles rs2803495 (AG + GG) (OR = 13.31, 95% CI = 5, 79-30.61, p &lt;0.001) and C allele rs2803496 (CT + CC) (OR = 18.99, 95% CI = 7.60-47.44, p &lt;0.001) are more likely to express TREML4 . Once again, the C allele was associated with higher levels of mRNA expression (OR = 3.98, 95% CI = 1.67-9.48, p = 0.002). The rs2803495 (AG + GG) and rs2803496 (CT + CC) variants were not related to the development of type 2 Diabetes Mellitus (DM2; p&gt; 0.05). However, patients who express TREML4 and are DM2 have higher levels of expression of TREML4 when compared to the control group (OR = 2.6, 95% CI = 1.19-5.72, p &lt;0.001). Patients with DM2 and rs2803495 (AG + GG) genotypes are more likely to express TREML4 (OR = 20.77, 95% CI = 2.29-188.41, p = 0.007). In silico analyzes showed that 8 miRNAs (hsa-miR-181a-5p, hsa-miR-200b-3p, hsa-miR-24-3p, hsa-miR-296-5p, hsa-miR-361-5p, hsa-miR- 423-5p, hsa-miR-486-3p and hsa-miR-708-5p) are expected to interact with TREML4 mRNA.The results suggest that mRNA expression of the TREML4 is associated with the presence of SNPs and increased in patients with AS with DM2 and that miRNAs may be involved in the regulation of the TREML4 being directly or indirectly involved in the pathophysiology of CVD being potential circulating biomarkers for early detection and/or individualized treatment of AS and CAD.
Abstract 11854: Longitudinal Improvement in Patient Reported Outcome Measures Following Supervised Exercise Therapy for Symptomatic Peripheral Artery Disease
Authors: Mohsin Chowdhury, Sahana Natesan, Alec Schmaier, Aishwarya Raja, Brett Carroll, Anna Krawisz, Betsy Rose, Eric A Secemsky
Journal: Circulation (2021)

Background: Symptomatic peripheral artery disease (PAD) is associated with severe morbidity and poor quality of life. Although data suggest that supervised exercise therapy (SET) may improve symptoms, few studies have evaluated longitudinal changes in patient reported outcomes among a real-world PAD population. Methods: Consecutive patients with symptomatic PAD treated at a single tertiary care center and referred for SET were enrolled. Patient reported outcomes were assessed at baseline and at 30 days, 6-months, and 1-year post-treatment through an electronic survey. The primary outcome was the change in the Peripheral Artery Questionnaire (PAQ) summary score from baseline to each time point. A change in PAQ summary score of &gt;8 has been established as clinically meaningful improvement. Results: Twenty-nine patients enrolled in the study received SET who had a mean baseline PAQ score 46.9±16.5. Following treatment, the mean PAQ score at 30 days, 6 months and 1 year were 61.0 ±20.7, 70.4 ±16.2 and 67.0 ±13.9, respectively (Figure 1), corresponding to a 14.1 point, 23.5 point and 20.1 point improvement in PAQ score. Conclusion: In this real-world assessment of patient reported outcomes following SET for the management of symptomatic PAD, treatment demonstrated consistent long-term improvement in patient reported outcomes as measured by the PAQ. Future work assessing the long-term durability of these changes is ongoing.
Abstract 12439: Sex-Specific Associations Between Adipose Depots With Subclinical Coronary Atherosclerosis and Cardiovascular Risk
Authors: Tasveer Khawaja, Sanjay Rajagopalan, Ian J Neeland, Sadeer Al-Kindi
Journal: Circulation (2021)

Introduction: Ectopic fat deposition (dysfunctional adipose tissue) is associated with atherosclerotic cardiovascular disease (ASCVD) risk. The value of adding fat distribution information to coronary artery calcium (CAC) score to predict ASCVD risk is unknown. Additionally, whether the association between fat distribution and CVD risk differs by sex is not well understood. Hypothesis: There are sex-specific relationships between adipose depots and CVD risk. Methods: We identified all participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent computed tomography of the chest and abdomen. We used machine learning models (logistic regression) to evaluate associations in men and women separately between 14 fat depot measurements encompassing visceral, subcutaneous, and ectopic fat (mean liver attenuation, total visceral, epicardial, intermuscular, intramuscular [paraspinous, rectus, psoas] and subcutaneous) and sex, non-zero CAC, and CVD risk using 10-fold cross-validation. Results: A total of 3163 individuals were included (1790 women and 1373 men). A model incorporating all fat depot variables had excellent discrimination of sex (AUROC = 0.88). In the entire cohort, our fat depot model had modest discrimination of non-zero CAC (0.69) and CVD events (0.58). The performance of CAC to predict CVD improved with the addition of fat depots (0.65 to 0.71). Women had higher AUROC for fat depots to predict non-zero CAC (0.63 vs 0.58) and CVD events (0.58 vs 0.52), which remained consistent in a model that includes CAC and fat (0.69 vs 0.66). Fat improved discrimination of CAC to predict CVD events more in women vs men (0.06 vs 0.03). The strength of association between various fat depots and sex differed between men and women (Figure). Conclusions: Visceral ectopic fat depots are associated with CAC and CV risk more strongly in women vs men. Future studies should focus on the sex-specific pathophysiology of cardiometabolic disease.
Abstract 10545: Hospital Teaching Status Increases the Frequency of Measurement of Right Heart Pressures in Patients Hospitalized for Heart Failure: A Nationwide Analysis
Authors: Jose S Aguilar-gallardo, Francisco ROMEO, Ashish A Correa, Johanna P Contreras
Journal: Circulation (2021)

Introduction: Measurement of right heart pressures is a useful, yet non-routine diagnostic tool whose indications in heart failure are not standardized. In this study, we investigated teaching status as an independent predictor of measurement of right heart pressures. Methods: This was a retrospective cohort study using the 2018 Nationwide Inpatient Sample that included adult patients with a primary diagnosis of heart failure that were admitted to urban hospitals. Rural hospitals were excluded. The primary outcome was measurement of right heart pressures. Secondary outcomes included performance of coronary angiogram, length of stay, total hospitalization charges. Multiple regression analysis was used to adjust for hospital bed size, region, and type of ownership, as well as the patient’s age, type of insurance, income quartile, Charlson Comorbidity Index, chronic obstructive pulmonary disease, pulmonary hypertension, and other relevant comorbidities with a p-value &lt;0.2 in univariate screen. Statistical analysis was performed using Stata 17.0. Results: A total of 1,117,134 (weighted) heart failure hospitalizations were studied, of which a total of 31,085 underwent measurement of right heart pressures. Multivariate regression analysis revealed that hospital teaching status was associated with a greater frequency of measurement of right heart pressures with an odd ratio (OR) 3.03 (95% CI, 2.38 to 3.89, p=0.000). The secondary outcomes of coronary angiogram, length of stay, and total hospitalization charges were also increased. Conclusions: Teaching status increases the frequency of measurement of right heart pressures in heart failure hospitalizations. This might highlight the need to standardize indications applicable across the spectrum of hospital settings.
TAMI-04. OLFACTORY RECEPTOR 5B21 DRIVES BREAST CANCER BRAIN METASTASIS THROUGH STAT3/NFΚB/CEBPΒ PATHWAY
Authors: Mao Li, Markus Schweiger, Daniel Ryan, Ichiro Nakano, Litia Carvalho, Bakhos Tannous
Journal: Neuro-Oncology (2021)

Abstract Olfactory receptors (ORs), responsible for the sense of smell, play an essential role in various physiological processes outside the nasal epithelium, including cancer. In breast cancer, however, the expression and function of ORs remain understudied. We established a breast cancer metastasis model by intracardiac injection of MDA-MB-231 (231P) in immunocompromised mice and produced a series of derivative cell lines from developed metastatic sites, including the brain-seeking clone (231Br). We examined the significance of ORs transcript abundance in primary and metastatic breast cancer to different tissues, including the brain, bone, and lung. While 20 OR transcripts were differentially expressed in distant metastases, OR5B21 displayed high expression in all three metastatic sites with respect to the primary tumor, especially in brain metastasis with 13 fold higher than the primary site. Metastatic clones showed distinguishing higher invasion biological characteristics compared to parental cells in vivo and in vitro. Knockdown of OR5B21 significantly decreased the invasion and migration of MDA-MB-231 Brain-seeking metastatic cell as well as metastasis to different organs, including the brain, while overexpression of OR5B21 had the opposite effect. Mechanistically, OR5B21 expression was associated with epithelial to mesenchymal transition through the STAT3/NFkB/CEBPβ signaling pathway. We propose OR5B21 (and potentially other ORs) as a novel oncogene contributing to breast cancer brain metastasis and a potential target for adjuvant therapy.
Chris Bartlett: expert in legionnaire’s disease and director of the Communicable Disease Surveillance Centre
Authors: Penny Warren
Journal: BMJ (2021)

Photo credit: Louise Bartlett

In January 1977 senior registrar Chris Bartlett arrived at a Portakabin in Colindale, north London, to start his new job. It was the unlikely headquarters of the new Communicable Disease Surveillance Centre (CDSC). Its staff of three (Bartlett, director Spence Galbraith, and a secretary) were tasked with the colossal job of infectious disease control for England and Wales. Bartlett became its director in 1988, overseeing its rapid growth to more than 250 staff and several regional centres. He trained a new generation of epidemiologists and public health doctors, managed emerging diseases such as legionnaire’s disease and AIDS, and set up crucial training links with Europe.

With an expansion of air travel in the 1970s, the UK population was vulnerable to infectious agents from beyond its borders. In the 1970s the numbers of malaria cases in the UK increased rapidly, and authorities were worried that new diseases—such as Lassa fever in west Africa—might reach our shores. Against this backdrop, an unnerving outbreak of smallpox occurred in London …
IMMU-29. B-CELL-BASED VACCINE PRODUCES GLIOBLASTOMA-REACTIVE ANTIBODIES THAT CONTRIBUTE TO TUMOR CLEARANCE
Authors: Brandyn Castro, Mark Dapash, David Hou, Aida Rashidi, Deepak Kanojia, Peng Zhang, Aurora Lopez-Rosas, Yu Han, Irina Balyasnikova, Roger Stupp, Jason Miska, Maciej Lesniak, Catalina Chang
Journal: Neuro-Oncology (2021)

Abstract Glioblastomas (GBM) are characterized by a strong immunosuppressive environment, contributing to their poor prognosis and limited therapeutic response to immunotherapies. B-cells represent a unique opportunity to promote immunotherapy due to their potential to kill tumors by both cellular and humoral immunity. To generate our B-cell-based vaccine (BVax) platform, we activated 41BBL+ B cells from tumor bearing mice or GBM patient blood with BAFF, CD40, and IFNg. We have previously demonstrated that BVax potentiates radiation therapy, temozolomide and checkpoint blockade in murine models of GBM via enhancement of CD8+ T-cell based immunity. The aim of this current study is to evaluate the humoral effector functions of BVax. We examined the antibody (Ab) repertoire in vivo from serum of tumor-bearing B-cell knockout mice treated with BVax or by ex vivo stimulation of patient-derived BVax. Upon systemic administration, BVax infiltrates the tumor where it differentiates into plasmablasts. Murine BVax- and BNaive-derived serum immunoglobulin generated in vivo showed that the majority of murine BVax-derived Ab were IgG isotype, while BNaive mainly produced IgM isotype. Transfer of IgG from BVax treated mice directly into tumors of recipient animals significantly prolonged their survival, demonstrating anti-tumor cytotoxicity directly through humoral immunity. Patient-derived BVax activated ex vivo showed a plasmablast phenotype and the Ab repertoire supports the previous findings seen in our murine model. Our work suggests BVax-derived IgGs role in antibody-dependent cellular cytotoxicity and improved survival in murine models. This function, in addition to its role in cellular immunity against GBM, renders BVax a potentially effective alternative immunotherapeutic option for GBM patients.
Abstract 10337: Initiative for Timely Acquisition of ECGs in Non-ICU Hospital Areas
Authors: Arjun S Patel, Jensen GALVIS, James Ruggero, Olivia Schanz, Truong-An Ho, Deepanjali Jain, Sara Peterson, Isha Mehta
Journal: Circulation (2021)

Introduction: In-hospital patients are a unique patient population with numerous co-morbidities and often atypical presentations for common cardiac problems. Delay in obtaining STAT ECGs on non-ICU (Intensive Care Unit) floors can have consequences ranging from delays in patient care to catastrophic morbidity and mortality for delayed diagnosis and treatment. Hypothesis: We hypothesize that there is high variability in the timely acquisition of obtaining inpatient EKGs in non-ICU areas regardless of whether there is a STAT or routine indication. Methods: We retrospectively reviewed 75 randomly selected non-ICU inpatient encounters for ECGs between January 2020 and March 2021. Of the 75 cases, 46 encounters met the criteria as non-ICU ECG encounters. The final data set included 24 routine ECG orders and 22 STAT ECG orders. Data gathered included time stamps for time of order, intended time for order to be completed, completion time and upload time in the EMR (electronic medical record). Results: STAT ECGs took a median of 1 hour and 42 minutes with times from the first and third quartiles ranging from 36 minutes to 2 hours and 58 minutes. Routine ECGs took a median of 3 hours and 17 minutes with times from the first and third quartiles ranging from 1 hour and 17 minutes to 4 hours and 30 minutes (Graph 1). Conclusion: Our results confirm that the acquisition of inpatient EKGs is highly variable and often delayed. Inpatient acquisition of ECGs should be standardized for patient safety and optimal outcomes. A protocol driven and multidisciplinary approach should be implemented to improve timely ECG acquisition.
Abstract 13697: Predictors of Prolonged Hospitalization (>48 Hours) and In-Hospital Mortality Among the Patients Admitted With Acute Pulmonary Embolism
Authors: Parth V Desai, Tauseef Akhtar, Axi Patel, Parth Shah, Sovik De Sirkar, Kevin Walsh, Nicolas Krepostman, Matthew Collins, Jawed Fareed, Amir Darki
Journal: Circulation (2021)

Introduction: Prolonged hospitalization leads to worse outcomes in patients admitted with acute pulmonary embolism (PE). However, there is a scarcity of data regarding the factors predisposing to p...
Abstract 8865: Multilevel Correlates of Received Social Support Among Heart Transplant Recipients in the International Bright Study: A Secondary Analysis
Authors: Martha Abshire Saylor, Kris Denhaerynck, Juliane Mielke, Patricia Davidson, Fabienne Dobbels, Cynthia Russell, Sabina M De Geest
Journal: Circulation (2021)

Introduction: Social support is critical in follow-up of patients after heart transplant (HTx) and positively influences well-being and clinical outcomes. Hypothesis: The purpose of this secondary analysis was to 1) explore received social support variation in HTx-recipients at country and center level (emotional and practical) and 2) to assess patient-, micro-, meso- and macro-level correlates. Methods: We examined data from the multi-level cross-sectional BRIGHT study, conducted in 36 HTx-centers in 11 countries. We used an 11-item instrument to measure received social support related to medication adherence with emotional and practical sub-scales. The Conceptual Model of Social Networks and Health guided selection of patient-, micro-, meso- and macro-level factors. Descriptive statistics for multi-level variables and bivariate analysis for emotional and practical dimensions of social support were conducted. Sequential multiple ordinal mixed logistic regression analysis was used to test multi-level models. Results: A total of 1379 adult HTx-recipients were included in this study. We identified variability at country and center level for both, emotional (country: 8.2%; center: 5.3%) and practical (country: 2.1%; center: 3.4%) dimensions of received social support. Independent correlates of emotional support at the micro level were patient-perceived level of chronic illness management and trust in the HTx-team, and at the patient level were female gender, living alone and depressive symptoms. Independent correlates of practical support were patients’ (micro) and clinicians (meso) perceived level of chronic illness management, and at the patient level were age, male gender and living alone. Conclusions: Social support in HTx-recipients varies by country, center and was associated with multi-level correlates. Qualitative and longitudinal studies are needed to understand influencing factors of social support for intervention development, improvement of social support and clinical outcomes.
Abstract 13185: Emergency Department Total and Out-of-Pocket Costs for Adults With Congenital Heart Disease in the United States
Authors: Jessica M Hong, Aarthi Sabanayagam, Ian S Harris, Peter Kouretas, Vaikom S Mahadevan, Shunji Sano
Journal: Circulation (2021)

Introduction: Despite a growing emergency department (ED) burden in the aging adult congenital heart disease (ACHD) population, data regarding the cost of ED visits remains unknown. This information could help inform appropriate resource allocation to reduce costs and improve outcomes for ACHD patients. Methods: We used a national commercial insurance database (IBM MarketScan) to characterize total and out-of-pocket (OOP) ED costs for ACHD patients with one or more ED visits in the year 2016. Multivariate linear regression analysis after adjusting for age &lt;40 years, gender, primary beneficiary status, employment, ACHD severity, cardiovascular (CV) and non-CV comorbidities was performed to determine variables associated with ED costs. Results: Of 3,579 ACHD patients with at least one ED visit, 53.4% were female, mean age was 35.5±14.4 years, and 33.2% had severe ACHD. Total (median; 25th, 75th) and OOP costs per visit were $2,004.79; $992.71, $4,034.63 and $232.32; $70, $695.30, respectively. Conditions with the highest per-visit total and OOP costs were neoplasm (total $6,186.89; $4,334, $13,005.19, OOP $329.20; $120, $1799.70), endocrine (total $3,467.51; $1,620.73, $9,878.38, OOP $428.99; $154.50, $1350.25), genitourinary (total $3,433.59; $1,739.97, $7,361.57, OOP $330.16; $120, $868.04), unclassified (total $3,370.04; $1,610, $7,793.22, OOP $347.50; $114.83, $1226.74), and symptoms, signs, and ill-defined (total $3,171.34; $1,740.55, $6,404.77, OOP $340.29; $100, $862.33). Factors independently associated with ED costs included comorbidities, primary beneficiary status, and employment (Figure). Conclusions: Non-CV comorbidities and noncardiac conditions during ED visits contribute substantially to ED costs among ACHD patients. Future studies to identify a collaborative, multidisciplinary care model to manage these noncardiac problems among ACHD patients might help reduce the overall burden of ACHD-related ED costs.
Protein Profiling Identify Distinct Tumor-Tissue Protein Expression Pattern Specific for Relapsing Diffuse Large B-Cell Lymphoma
Authors: Maja Ludvigsen, Diani Wilken, Marja-Liisa Karjalainen-Lindsberg, Klaus Beiske, Lars Pedersen, Jan Delabie, Francesco d'Amore, Harald Holte, Sirpa Leppa, Judit Jørgensen, Bent Honoré
Journal: Blood (2021)