tbuckley/cabot-search huggingface dataset:
Abstract 11424: SARS-CoV-2 B.1.1.7 Variants Do Not Increase Risk of Subsequent Cardiovascular Disease
Authors: Stacey Knight, Gabriel Larsen, Will Sinclair, Ryan Rupper, Tami L Bair, Heidi T May, Bert K Lopansri, John F Carlquist
Journal: Circulation (2021)

Background: The SARS-CoV-2 B.1.1.7 variant, also known as the UK or alpha variant, carries the spike 69/70 deletion mutation and has been reported to be more contagious and possibly more virulent than other variants. This study examines follow-up cardiovascular outcomes for patients infected with deletion-carrying SARS-CoV-2 alpha variant. Methods: From October 2020 to May 2021, all positive SARS-CoV-2 samples at Intermountain Healthcare were tested for the 69/70 deletion (n=92822). Patient characteristics, COVID-19 treatments, and follow-up outcomes were extracted from Intermountain records. Cox hazard regression analysis with multivariable adjustment was used to determine risk of subsequent major cardiovascular adverse event outcomes (MACE), which included all-cause death, heart failure (HF), and hospitalization for coronary artery disease (CAD) or atrial fibrillation (AF). Results: Overall, 4.2% of patients testing positive for the SARS-CoV-2 virus carried the deletion mutation with prevalence increasing with time, ranging from 1.3% in October to 61.0% in May. Baseline characteristics, treatments, and outcomes stratified by non-mutant and deletion mutation status are shown in the Table. While the mutation did result in higher rates of COVID hospitalization (adjusted OR=1.68, p&lt;0.001), there was no difference in overall MACE after adjustment by baseline characteristics and risk factors. There was a non-significant trend toward an increased rate of all-cause death in patients carrying the mutant variant (adjusted HR=1.90, p=0.12). Conclusions: The SARS-CoV-2 deletion mutant, while resulting in an increased risk of COVID hospitalization and a trend toward increased death, did not increase the risk of subsequent CVD. Because of the recent emergence of the variant the long-term effects are not known. Thus, it remains important to minimize risk of exposure. Moreover, long-term surveillance of subsequent CVD risk is warranted.
Abstract 11890: Timing of Surgery for Infective Endocarditis: A Network Meta-Analysis
Authors: Surya Aedma, Anant Naik, Mounika Reddy Vadiyala, pranav mahajan, Raja S Jadav, Rahul Gupta, Sugandhi Mahajan, Keirthana Aedma, Sanjay Mehta, Arun K Kanmanthareddy
Journal: Circulation (2021)

Introduction: Infective endocarditis (IE) is associated with in-hospital mortality of 15-30%. Surgery is recommended in approximately 50%. The best available evidence from meta-analyses has demonstrated benefit of early surgical intervention (SI) for the management of IE. However, the timing of surgery has not been further sub-stratified and internally compared Methods: We performed a frequentist network meta-analysis adhering to PRISMA Guidelines. Observational studies comparing SI for infective endocarditis at different time points - SI performed &lt;48 hours of diagnosis, 2-7 days, 7-14 days, 14-28 days, 28+ days - were included for analysis. In-hospital mortality, all-cause mortality, in-hospital embolic events, and recurrence of endocarditis were used as outcome variables. All analysis was performed on R, using the open-source net meta-package. Results: A total of 28 studies met our inclusion criteria. Figure 1A shows forest plots for each outcome. SI at any time period improved all-cause mortality. However, only Surgery &gt; 21 days resulted in improved in-hospital mortality (OR = 0.19 (0.04-0.85)). Intervention at any specific surgical window did not improve in-hospital embolic events or recurrence of endocarditis. Figure 1B shows SUCRA-dependent hierarchical ranking. Surgery greater than 21 days (S = 0.9443), followed by Surgery &lt; 48 hours (S = 0.7133) was superior to other intervention windows. Surgery &lt; 48 hours also was found to have a higher rank for in-hospital embolic events (S = 0.947). Conclusions: Our results supplement the existing society consensus statements and guidelines to opt for early SI, by positing the value of SI within 48 hours. If the patient is stable SI can be performed after 21 days for better in hospital mortality rates. Randomized control trials need to be performed to evaluate further.
Abstract 12360: A Pilot Study of Remote Patient Monitoring for Hypertension in Primary Care
Authors: Stephen D Persell, Lauren Anthony, Yaw Peprah, Lucia Petito, Ji Young Lee, Jim Li, Hironori Sato
Journal: Circulation (2021)

Introduction: Out-of-office BP should guide hypertension care. CMS now covers remote patient monitoring (RPM). We assessed uptake and initial effects of introducing RPM. Hypothesis: At 6-months, hypertensive Medicare patients in RPM clinics would have greater antihypertensive medication intensification, better blood pressure control (NQF 0018), and lower SBP at last office visit. Methods: This was a pragmatic observational study in primary care in a single health system. We integrated Omron VitalSight TM RPM into the system’s EHR to enable transmission of BP and pulse from a BP monitor into the EHR without manual entry. We oriented two clinics [17 primary care physicians (PCPs)] using meetings and written material, leaving the decision to order RPM to PCPs. We compared their patients to controls from other clinics matched by age, sex, BP, and number of office visits in the prior year. We examined outcomes in: (P1) those with poor BP control at baseline—last two office BP ≥140/90, and (P2) all hypertensive patients (diagnosed hypertension or last office BP ≥140/90). Additional criteria included: age 65-85 years; ≥1 office visit in past year; and absence of persistent atrial fibrillation, CKD stage IV or V, or dementia. Results: RPM implementation was feasible. In P1, 207 intervention patients had mean (SD) baseline BP 151.7 (10.1) / 79.7 (8.1) mmHg, and 828 controls had BP 151.4 (10.6) / 79.5 (8.9) mmHg. In P2, 2356 intervention patients and 4712 controls had corresponding mean baseline BPs of 131.3 (14.7) / 74.9 (8.3) and 131.3 (14.7) / 74.8 (8.8) mmHg. During 6 months, PCPs ordered RPM for 14 (6.8%) P1 patients and 78 (3.3%) P2 patients. In both P1 and P2, NQF 0018 satisfaction was higher at RPM-eligible clinics (p = 0.044, 0.020 respectively) (Table). Medication intensification did not differ in P1 or P2. Conclusions: RPM uptake was modest. Controlling High Blood Pressure at 6 months favored the RPM intervention and was likely due to factors other than medication intensification.
Treatment of Locally Advanced/Metastatic Colorectal Cancer
Authors: Alan P. Venook, Christopher G. Willett
Journal: Journal of the National Comprehensive Cancer Network (2021)

Few treatment advances have been observed in recent years for the treatment of advanced colorectal cancer (CRC). The goal remains to find approaches beyond FOLFOX and bevacizumab that will prolong remission. Immunotherapy for patients with microsatellite instability–high tumors represents progress, but this is a very small subset and approximately 30% of patients will not experience response. In locally advanced CRC, good long-term outcomes and manageable toxicity are being achieved with contemporary treatment strategies. Total neoadjuvant therapy, which incorporates induction or consolidation chemotherapy, has improved the treatment of patients with rectal cancer and is now a standard of care, although optimal sequencing is still being debated. Nonoperative management is an emerging option for sphincter preservation, and ongoing studies are evaluating the omission of radiation in select patients.
Abstract 9397: Sonothrombolysis Improves Cardiac Segmental Contractility, Myocardial Perfusion and Baroreflex Gain in Patients With ST-segment Elevation Myocardial Infarction (stemi) in Long-Term Follow-Up
Authors: Luciene F Azevedo, Bruno Carter C Borges, Edgar Toschi-Dias, Larissa Ferreira-santos, Raphaela V Groehs, Jeane M Tsutsui, Amisa Guimaraes, marco C oliveira, Paola E smanio, Thomas R Porter, Wilson Mathias
Journal: Circulation (2021)

Sonothrombolysis (Sono) has improved microvascular obstruction, global contractility and infarct area after STEMI. Objective: To evaluate the long-term effect of Sono and its physiologic mechanisms in a subgroup of 51 STEMI patients (percutaneous coronary intervention-PCI (N=24) and PCI+Sono (N=27)) from previous randomized study. All patient were treated with PCI and those also treated with Sono received frequent image-guided diagnostic high mechanic index impulses applied to the myocardial contrast-enhanced areas (microbubbles) in the apical views (1.8 MHz; 1.1 to 1.3 MI; &lt;5-μ pulse duration). Evaluations were at pre-treatment, 1 month (ultrasound-US with contrast agent) and at averaged 34±17 months after STEMI (US with contrast agent; cardiac and peripheral sympathetic activity by means of 123 I-MIBG cardiac scintigraphy and microneurography; baroreflex gain of heart rate (HR) control by means of transfer function analysis). (For significance: P level ≤ 0.05). US values are on table. Adding, PCI+Sono showed lower left ventricular end-diastolic volume (LVEDV) remodelling (22±36 vs. 44±42%, P&lt;0.05). Cardiac scintigraphy showed similar late Heart/Mediastinum ratio and similar washout rate between groups. Muscle sympathetic nervous activity was also similar in both groups. PCI+Sono showed higher baroreflex gain of HR control (8±3 vs. 6±2 ms/mmHg, P=0.05), indicating an improved baroreflex sensitivity. In addition, perfusion score index correlated positively with wall motion score index (r=0.97, P&lt;0.001) and washout rate (r=0.30, P=0.04). LV ejection fraction correlated negatively with wall motion score index (r=-0.53), perfusion score index (r=-0.48) and LVEDV (r=-0.29) (P&lt;0.05). In conclusion, Sono added to PCI improved contractility and myocardial perfusion in STEMI. Despite high level of sympathetic activity, baroreflex gain of HR was ameliorated in PCI+Sono patients, probably due to better myocardial perfusion and lower LV remodelling.
EPID-02. COUNTY MEDIAN FAMILY INCOME AS PROGNOSTIC FACTOR IN NON-SMALL-CELL LUNG CANCER WITH BRAIN METASTASES AT PRESENTATION: A POPULATION-BASED STUDY
Authors: Ignacio Jusue-Torres, Alicia Hulbert, Jehad Zakaria, Kathy S Albain, Courtney Hentz, Edward Melian, Jigisha P Thakkar, Vikram C Prabhu
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION The purpose of this study was to characterize the impact of household income disparities in the survival of patients with non-small cell lung cancer (NSCLC) presenting with brain metastasis on a population-based level. METHODS This is a population-based cohort study using the SEER database from 2010-2016 including 15,808 NSCLC patients presenting with brain metastasis. Two-tailed log-rank test was used to compare overall survival between groups and association with survival was quantified using hazard ratios (HR) with 95 % confidence intervals (CI) assessed with univariate and multivariate Cox proportional hazard models. RESULTS Patients living in low-income counties had a median survival of 4 months when compared to 5 months for patients living in high-income counties respectively (p&amp;lt; 0.0001). Patients living in first and second bottom quartiles had a median survival of 4 months and 5 months and 6 months for the third and fourth top quartiles, respectively (p&amp;lt; 0.0001). The 1-, 2- and 5-year survival rates for living in the lower household income quartile were 21, 10 and 3% respectively, for the second quartile 24, 10 and 3%; for the third quartile 28, 14 and 4% and for the top fourth quartile 31, 17 and 4% respectively. Multivariate cox proportional hazard analysis adjusted for age, gender, race, hispanic ethnicity, marital status, insurance status, percentage of high school education in the patient’s county, histology, presence of lung metastasis, bone metastasis, liver metastasis, radiation received, surgery performed, and chemotherapy received showed that living in higher quartile household income county is associated with decrease mortality risk (p &amp;lt; 0.0001) HR 0.87 95% CI (0.82-92). CONCLUSION This population-based study suggests that living in higher median household income counties is associated with increased survival time and reduced risk of mortality for patients with NSCLC who have brain metastases present at diagnosis, independent of other factors.
Limitations in Research on Maintenance Treatment for Individuals With Schizophrenia
Authors: Mark Abie Horowitz, Alex Macaulay, David Taylor
Journal: JAMA Psychiatry (2021)

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Abstract 14052: Outcomes of Radiofrequency Transcatheter Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy. A Systematic Review and Meta-Analysis
Authors: Azka Latif, Muhammad J Ahsan, Abbis Jaffri, Claire C Willman, vikas kapoor, Mohsin Mirza, Michael H Kim
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM). Radiofrequency transcatheter ablation (RFCA) for AF in patients with HCM is beneficial, however, its efficacy and safety is not well characterized. This meta-analysis aimed to access the efficacy of RFCA in patients with HCM and concomitant AF. Methods: PubMed, Embase, Cochrane, ClinicalTrials.gov, and Google Scholar were searched for studies evaluating the efficacy of RFCA for AF in patients with HCM from January 1, 2000, until April 2021. The outcomes data regarding the efficacy of RFCA after a single or multiple procedures was assessed. The analysis was performed using a random-effects-model using the Mantel-Haenszel method and results presented as 95% confidence interval using STATA version 15.1 software. Results: Sixteen observational (N=769) studies were included. The mean time after the first procedure was ≥12 months and the meantime after multiple procedures was 3 years. The mean age was 57.5+/-8.3 years and 30% of patients were women. Single-procedure freedom from AF at the latest follow-up was 38.67% (95% CI: 33.38-44.10%, I2 =54.55%) reported by 15/16 studies (Fig 1A). With multiple procedures, the final success rate was 45.648% (95% CI: 37.52-53.90, I2=75.9%) reported by 15/16 studies (Fig 1B) Conclusions: RFCA of AF in patients with HCM appears to be safe and feasible, although these patients have lower overall success rates compared to a more typical AF ablation population. HCM patients also require multiple procedures to gain intermediate success rates.
IMMU-34. CAMKK2 PROMOTES AN IMMUNOSUPPRESSIVE PROGRAM AND CHECKPOINT BLOCKADE RESISTANCE IN THE GLIOBLASTOMA TUMOR MICROENVIRONMENT
Authors: William Tomaszewski, Jessica Waibl-Polania, Luigi Racioppi, Luis Sanchez-Perez, Gunn Michael, John Sampson
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Immunotherapy has demonstrated efficacy in several cancers but has shown only modest effects in Glioblastoma (GBM). This is linked to the anti-inflammatory nature of the tumor microenvironment (TME) and the pro-tumor functions of brain native cells. Targeting stromal cells, such as tumor associated macrophages (TAMs) and neurons, is a promising approach. Re-analysis of human and murine brain single cell-RNAseq (scRNAseq) datasets shows Calmodulin Dependent Kinase Kinase 2 (CaMKK2) is highly expressed in both neurons and TAMs. Loss of CaMKK2 polarizes TAMs to an immunostimulatory phenotype and reduces pro-tumor neuronal functions. Thus, we hypothesize that CaMKK2 promotes the pro-tumor nature of the GBM TME and immunotherapy resistance. RESULTS Murine GBM was orthotopically implanted into wild-type and CaMKK2-/- mice. CaMKK2-/- mice exhibited significantly prolonged survival. To determine if anti-tumor immune function was enhanced, we probed the TME using flow cytometry and scRNAseq. CaMKK2-/- mice showed increased abundance of precursor exhausted, potentially immune checkpoint blockade (ICB) responsive, CD8 T cells. Furthermore, T cell depletion abrogated the survival benefit observed in CaMKK2-/- mice. Considering these T cell phenotypes, we treated CaMKK2-/- mice with ICB, and indeed they were sensitive. To determine if the CaMKK2-/- survival phenotype and ICB response depended on CaMKK2 expression in hematopoietic or in non-hematopoietic cells, we utilized a reciprocal chimera model. Loss of CaMKK2 in the non-hematopoietic cells was more vital for survival and ICB response than in hematopoietic cells, suggesting a potential novel and unique role for CaMKK2 in brain native cells - potentially neurons - in coordinating ICB resistance. CONCLUSIONS We find that CaMKK2 exacerbates mortality and drives ICB resistance by limiting the anti-tumor response in GBM via both hematopoietic and brain native cells. Our findings identify a novel therapeutic target for GBM, and a unique role for CaMKK2 in the TME.
Abstract 11420: Platelet Activity Mediates Increased Cardiovascular Risk in Patients with End-Stage Kidney Disease and Peripheral Artery Disease
Authors: Lucas Cofer, Qandeel Soomro, Yuhe Xia, Elliot Luttrell-Williams, Khrystyna Myndzar, Caron Rockman, David Charytan, Jeffrey S Berger
Journal: Circulation (2021)

Background: End-stage kidney disease (ESKD) and peripheral artery disease (PAD) are frequently co-prevalent and each associated with increased cardiovascular (CV) risk. Platelets drive PAD pathogenesis and mediate atherothrombosis. Their function and influence on CV risk in ESKD remain unclear. We hypothesized that ESKD is associated with heightened platelet activity and incident cardiac and limb events in patients with PAD. Methods: The Platelet Activity and Cardiovascular Events study enrolled 289 patients with PAD undergoing lower extremity revascularization (LER). We measured platelet activity prior to LER via light transmission aggregometry in response to submaximal ADP, collagen, serotonin, epinephrine, and arachidonic acid. We followed patients for a median of 18 months for a primary endpoint of major adverse CV event (MACE; MI, stroke, death) and a secondary composite of major adverse CV or limb event (MACLE; MACE or acute limb ischemia). Results: Among enrolled subjects, 25 (9%) had ESKD. They were younger and more likely to have a history of coronary artery disease (CAD), heart failure, and critical limb ischemia (CLI) than those without ESKD (P&lt;0.05 for each). Aggregation in response to epinephrine 2.0 uM after 5 minutes and at maximum was greater in those with compared to without ESKD (61% vs. 48%; P=0.004 and 77% vs. 60%; P=0.001, respectively). After multivariable adjustment, patients with vs. without ESKD were at greater risk for CV events ( Figure ). Platelet aggregation in response to submaximal epinephrine stimulation had a 32% and 45% mediating effect on the excess risk for MACE and MACLE, respectively, associated with ESKD ( Figure ). Conclusions: In patients with PAD, ESKD was associated with increased platelet aggregation in response to submaximal epinephrine that partially mediated increased risk for incident cardiac and limb events. Platelet activity appears to be an important mechanism underlying CV risk in ESKD.
Abstract 10432: Simultaneous Recording of Skin Sympathetic Nerve Activity and Blood Pressure in Ambulatory Outpatients with Postural Orthostatic Tachycardia Syndrome
Authors: Xiao Liu, Carine Rosenberg, Andrew Lee, Mary E Leier, Harrison Dinh, Florian Rader, Peng-Sheng Chen
Journal: Circulation (2021)

Introduction: neuECG is a method to simultaneously record ECG and skin sympathetic nerve activity (SKNA). Postural orthostatic tachycardia syndrome (POTS) is known to be associated with increased cardiac sympathetic norepinephrine release. Hypothesis: Average SKNA correlates positively with heart rate (HR) and blood pressure (BP) in POTS patients. Methods: We used Bittium Faros 180 Holter Monitor (sampling rate 1,000 Hz) to record neuECG and SpaceLab OnTrak arterial BP monitor (ABPM) to record BP simultaneously over 24-hr in 20 POTS patients (19 women, 38±12 years old). The Faros signals were high pass filtered at 300 Hz to display the SKNA. The same original signals were bandpass filtered 0.05-150 Hz to display ECG. BP was measured every 30-min when awake (7AM to 9 PM) and hourly at night (9 PM to 7 AM). Results: Fig 1 shows an example of typical recording from a 38-year-old woman. Panel A shows average SKNA (aSKNA) 1-min prior to HR and BP measurement. The overall successful ABPM measurement was 90% with average BP of 126/75 mmHg. B shows bursts of SKNA in daytime (red dot in A), but no bursts at night (blue dot in A). C shows a positive correlation between HR, systolic BP (SBP) diastolic BP (DBP) and mean BP (MBP) with aSKNA. For all patients studied, 16 of 20 showed positive correlation between MBP and aSKNA (r=0.559±0.152, p&lt;0.05 for all) and 15 of 20 showed positive correlation between HR and aSKNA (r=0.511±0.175, p&lt;0.05 for all). The nocturnal aSKNA averaged 0.919±0.059 μV (N=17) and 1.060±0.215 (N=3) (p&lt;0.001) in patients with and without nocturnal dip, respectively. However, the overall 24-hr aSKNA (1.036±0.120 vs 1.044±0.095, μV) was not different between these two groups. Conclusions: aSKNA positively correlated with BP and HR in ambulatory outpatients with POTS. High aSKNA at night was associated with nocturnal non-dipping of BP.
Abstract 10712: Mrna COVID Vaccines Dramatically Increase Endothelial Inflammatory Markers and ACS Risk as Measured by the PULS Cardiac Test: a Warning
Authors: Steven R Gundry
Journal: Circulation (2021)

Our group has been using the PLUS Cardiac Test (GD Biosciences, Inc, Irvine, CA) a clinically validated measurement of multiple protein biomarkers which generates a score predicting the 5 yr risk (...