tbuckley/cabot-search huggingface dataset:
Abstract 13792: Association of Immunocompromised State With Coronary Microvascular Dysfunction in Patients With Well-controlled HIV
Authors: Leah Rethy, Joseph Kern, Chad Achenbach, Michael Angarone, Stephen Dvorak, Christopher Konstantelos, Jay A PANDIT, Ravi B Patel, Juliet Ryan, Arjun Sinha, Babafemi Taiwo, Li-ming Gan, Matthew J Feinstein, Sanjiv J Shah
Journal: Circulation (2020)

Introduction: Patients with HIV have an elevated risk of cardiovascular disease (CVD) that may be partially driven by inflammation and residual immune dysfunction despite treatment with antiretroviral therapy (ART). Coronary microvascular dysfunction (CMD) is an important pathophysiological link between inflammation, immune dysfunction, and CVD and may provide mechanistic insight into CVD risk among HIV+ patients. Methods: We recruited 3 groups of adults aged 40-80 years free of CVD: HIV with evidence of prior/current immunocompromise (n=17), HIV without immunocompromise (n=19), and HIV- controls. All HIV+ participants were on ART and had suppressed viral loads. All controls were on HIV pre-exposure prophylaxis (PrEP). Immunocompromise was defined as nadir CD4 count &lt;200 cells/μL or current CD4 count &lt;500 cells/μL. Participants underwent Doppler echocardiography with coronary flow velocity measurement in the distal left anterior descending coronary artery at rest and during adenosine infusion. CMD was defined as coronary flow reserve (CFR) &lt; 2.50. Multivariable linear regression models assessed the association of HIV group with CFR. Results: Of 51 individuals who underwent CFR testing, median (IQR) age was 54 (46-58) and 92% were male. CFR was 3.71 (2.90-4.72) in controls, 3.49 (2.52-4.20) in HIV+/ immunocompromise-, and 2.35 (2.12-2.92) in HIV+/ immunocompromise+ (p=0.002). CMD was present in 7% of controls, 21% of HIV+/immunocompromise-, and 53% of HIV+/immunocompromise+ (p= 0.01). Compared with controls, HIV+/immunocompromise+ was significantly associated with lower CFR after multivariable adjustment ( Table ). Conclusions: HIV+ patients with current/prior immunocompromise free of CVD had high prevalence of CMD and had significantly lower CFR compared with controls on PrEP. Future studies should investigate CMD as a possible target for CVD prevention in HIV+ patients, particularly those with a prior or current immunocompromised state.
A Novel Prognostic Model for Primary Gastric Diffuse Large B-Cell Lymphoma in the Rituximab Era, Integrating EBV Harboring on Tumor Cells
Authors: Eri Ishikawa, Tsutomu Tanaka, Kazuyuki Shimada, Hidemi Goto, Shigeo Nakamura, Seiichi Kato
Journal: Blood (2017)
Pembrolizumab for patients with leptomeningeal metastasis from solid tumors: efficacy, safety, and cerebrospinal fluid biomarkers
Authors: Jarushka Naidoo, Karisa C Schreck, Wei Fu, Chen Hu, Alexander Carvajal-Gonzalez, Roisin M Connolly, Cesar A Santa-Maria, Evan J Lipson, Matthias Holdhoff, Patrick M Forde, Christopher Douville, Joanne Riemer, Amanda Barnes, Kristin J Redmond, Lawrence Kleinberg, Brandi Page, Nafi Aygun, Kenneth W Kinzler, Nickolas Papadopoulos, Chetan Bettegowda, Arun Venkatesan, Julie R Brahmer, Stuart A Grossman
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The benefit of immune checkpoint inhibitors (ICIs) in patients with leptomeningeal metastases (LMM) is unknown. Methods We undertook a phase II trial of pembrolizumab in patients with LMM from solid tumors. Eligible patients had radiologic/cytologic LMM and Eastern Cooperative Oncology Group performance status 0–1. Pembrolizumab was administered intravenously at 200 mg q3W until disease progression/unacceptable toxicity. The primary endpoint was central nervous system (CNS) response after four cycles, defined radiologically/cytologically/clinically. Serial cerebrospinal fluid (CSF) was assessed for tumor-derived DNA (t-DNA) aneuploidy and cytokines. Results Thirteen of a planned 16 patients were treated between April 2017 and December 2019. The study closed early for poor accrual. Median age was 57 years (range: 22–79). Sixty-two percent of patients had tumors not traditionally ICI-responsive (hormone-receptor (HR)-positive breast carcinoma=39%; high-grade glioma=23%), while 38% had ICI-responsive tumors (non-small cell lung cancer (NSCLC)=23%, head and neck carcinoma=8%, cutaneous squamous carcinoma (CSC)=8%). CNS response was observed in 38% of patients at 12 weeks (95% CI 13.9% to 68.4%) by pre-defined criteria and LM-RANO, and 2 achieved durable complete responses (CSC=1, overall survival (OS) 3+ years; NSCLC=1, OS 9 months). Median CNS progression-free survival and OS was 2.9 months (95% CI 1.3 to NR) and 4.9 months (95% CI 3.7 to NR), respectively. Grade 3+ treatment-related adverse events occurred in 15% of patients. Sensitivity for LMM detection by t-DNA and cytopathology was 84.6% (95% CI 54.6% to 98.1%) and 53.9% (95% CI 25.1% to 80.8%), respectively. Pre-therapy and on-therapy CSF cytokine analysis demonstrated complete responders clustered together. Conclusions Pembrolizumab conferred a 38% CNS response rate in patients with LMM, a tolerable safety profile, and deep responses in selected patients with ICI-responsive tumors. CSF t-DNA may be sensitive for LMM detection, and immunologic subsets of CNS response warrant further study. Trial registration number NCT03091478
Abstract 16898: Clinical Implementation of Pharmacogenomics Testing to Guide P2Y12 Inhibitor Use in Older Adults With Acute Coronary Syndrome: Insights From a Prospective Pilot Study
Authors: Sagune Sakya, CHRISTOPHER J Regan, Lionel Picot-Vierra, Ralph J Riello, Lydia Tran, Wade Schulz, Kim G Smolderen, Carlos Mena-Hurtado, Rebecca Pulk
Journal: Circulation (2020)

Introduction: CYP2C19 testing is a known pharmacogenomics application to identify patients who can activate clopidogrel. Evidence-based guidelines now support second generation P2Y12 inhibitors over clopidogrel for the management of acute coronary syndrome (ACS). However, continued broad use of clopidogrel within our health-system indicated the potential value of pharmacogenomic testing to guide P2Y12 inhibitor prescribing. This study aimed to evaluate the clinical application of pharmacogenomic testing within a cardiovascular population and identify optimizations to the implementation process. Methods: This was a prospective, descriptive cohort pilot study at a large academic health-system. A high-impact pilot population included patients 65 years and older admitted for ACS who underwent percutaneous coronary intervention (PCI). Pharmacists identified eligible patients and made genomic-guided P2Y12 inhibitor recommendations for each patient. Surrogate markers of clinical impact included clopidogrel prescribing rates and quantification of active medication-gene interactions. Process indicators included acceptance rate of recommendations. Results: A total of 151 patients were included. At the time of result return, 46% of patients were on clopidogrel. Of these patients, 27% were identified as poor or intermediate metabolizers and were indicated for a change in therapy. The acceptance rate of genomic-guided recommendations was 42%. Identified barriers to uptake included result turnaround time limiting application of findings and unclear responsibility of follow-up. Conclusions: Results from this real-world study support implementation of CYP2C19 testing to guide P2Y12 inhibitor use. Identifying candidates for clopidogrel use through testing has potential clinical and cost benefits, but further studies are needed. Process optimizations are required to address implementation barriers and increase follow-up on actionable results.
Abstract 15429: One-year Patterns of Home Blood Pressure Monitoring Using Consumer-purchased Wireless Devices in the Health Eheart Study
Authors: Yaguang Zheng, Yanfu Zhang, Heng Huang, Geoffrey H Tison, Lora E Burke, Jeffrey Olgin, Gregory M Marcus, Mark J Pletcher
Journal: Circulation (2020)

Introduction: Engagement with home blood pressure monitoring (HBPM) usually declines over time; however, published studies have not described inter-individual variability of HBPM behaviors. We aimed to describe different 1-year patterns of HBPM behaviors, identify predictors of those patterns, and examine the association of HBPM behaviors with BP levels over time. Methods: We analyzed BP records from the Health eHeart (HeH) Study, an ongoing prospective e-cohort study, limiting our analysis to participants with a wireless consumer-purchased device that transmitted date-and time-stamped BP data to the HeH server through a full 12 months of observation starting from the first day they used the device. Participants received no instruction on device use. We applied clustering analysis to identify 1-year HBPM patterns. Results: The sample (N=2099) had a mean age of 52.0±12.0 years and BMI of 28.9±6.5 kg/m 2 ; most were male (89.1%) and White (88.6%). Using clustering algorithms, we found that a model with three patterns fit the data well (Figure); 69.7% were Sporadic Users, 21.2% were Weekly Users, and only 9.1% were Daily Users. Daily Users were older, unemployed, lower income, and more likely to have diabetes, coronary heart disease, and a history of myocardial infarction (p&lt;.05 for all). Daily Use was also associated with lower BP levels that remained persistently lower than the Weekly or Sporadic Users throughout the year (estimated mean ± standard error, respectively: SBP: 126.2±0.8 vs.128.8±0.5 vs.128.3±0.3, p=.036; DBP: 76.3±0.6 vs. 80.2±0.4 vs. 79.9±0.2, p&lt;.001). Conclusion: We identified 3 distinct HBPM use patterns, with nearly 10% sustaining a daily use pattern that was associated with lower BP levels despite being in socially and medically higher risk groups.
Abstract 13149: Survival Benefit With Higher Dose Tafamidis in Patients With Hereditary and Wild-type Transthyretin Amyloid Cardiomyopathy
Authors: Sanjiv J Shah, Balarama Gundapaneni, Marla B Sultan, Giampaolo Merlini
Journal: Circulation (2020)

Introduction: Tafamidis was shown to be an effective treatment for patients with both hereditary/variant (ATTRv) and wild-type (ATTRwt) transthyretin amyloid cardiomyopathy (ATTR-CM) in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). The higher dose of tafamidis (80 mg) was shown to be the optimal dose and is approved for the treatment of ATTR-CM. We hypothesized that longer term follow up would further characterize the benefit of higher dose tafamidis. Methods: In ATTR-ACT, patients were randomized to tafamidis meglumine (80 mg or 20 mg) or placebo for 30 months. Patients who completed ATTR-ACT were eligible to enroll in a long-term extension study (LTE) in which placebo-treated patients were randomized to tafamidis 80 mg or 20 mg. As of 20 July, 2018, all patients in the LTE were transitioned to tafamidis free acid 61 mg (a new formulation bioequivalent to tafamidis 80 mg). All-cause mortality (as of 1 Aug, 2019) was assessed in patients treated with tafamidis 80 mg in ATTR-ACT and the LTE who transitioned to tafamidis free acid 61 mg (tafamidis 80/61 mg) compared with patients treated with placebo in ATTR-ACT who transitioned to tafamidis in the LTE (placebo/tafamidis). Results: There were 85 ATTRv patients (42 tafamidis 80/61 mg [median treatment duration 53.8 months]; 43 placebo/tafamidis [48.1 months]) and 268 ATTRwt patients (134 tafamidis 80/61 mg [51.7 months]; 134 placebo/tafamidis [51.6 months]).In ATTRv patients, there were 25 (59.5%) deaths with tafamidis 80/61 mg and 30 (69.8%) deaths with placebo/tafamidis; a 39.8% reduction in risk of all-cause mortality with tafamidis 80/61 mg (hazard ratio vs placebo/tafamidis [95% CI], 0.6020 [0.3473, 1.0435]; P=0.0706). In ATTRwt patients, there were 50 (37.3%) deaths with tafamidis 80/61 mg and 78 (58.2%) deaths with placebo/tafamidis; a 40.1% reduction in risk of all-cause mortality with tafamidis 80/61 mg (0.5992 [0.4186, 0.8577]; P=0.0051). Conclusions: While there were fewer ATTRv patients in the study, longer-term follow-up demonstrated similarly improved survival with higher dose tafamidis in both ATTRv and ATTRwt patients. These data further highlight the benefit of tafamidis (80 mg meglumine or 61 mg free acid) in all patients with ATTR-CM.
Abstract 16757: Immunomodulatory Hydrogel Promotes Survival of Mesenchymal Stem Cells in a Rat Model of Myocardial Infarction
Authors: Michaela Olthoff, Naveen Nagaiah, Federico Franchi, Weiang Yan, Sanjiv Dhingra, Ramasamy Paulmurugan, Martin Rodriguez-Porcel
Journal: Circulation (2020)

Introduction: Stem cell (SC) therapy is a potential method of repairing the heart after injury. However, SCs have been shown to have poor survival after transplantation, at least in part, due to a hostile pro-inflammatory ischemic myocardium. Thus, there is significant interest in the identification of strategies that can increase the retention/survival of SCs after transplantation. Here we seek to investigate whether the use of an immunomodulatory hydrogel, containing anti-inflammatory sinapic acid (SA), promotes the survival of SCs after transplantation. Methods: Myocardial infarction was induced in rats followed by the delayed delivery of A) mesenchymal stem cells (MSCs), B) MSCs in a hydrogel without SA or C) MSCs in a hydrogel containing SA (10μM). Delivery of MSCs (7.5 x 10 5 in 30μL) occurred 7 days after MI, representing the subacute stage and to minimize acute inflammation. Survival of MSCs, stably expressing firefly luciferase under the constitutive CMV promoter, was followed longitudinally using bioluminescence imaging. Results: Panels A-C provide representative images of the viability of MSCs in different groups, with the quantification shown in panel D. There were no differences in survival when MSCs were delivered alone (A) or in a hydrogel without SA (B). However, the survival of MSCs was significantly increased when they were transplanted in a hydrogel with the anti-inflammatory SA (C). Conclusions: Here we provide evidence of the potential for an immunomodulatory hydrogel to enhance the viability of MSCs after infarction, which may lead to improvement of cardiac function. Furthermore, use of this hydrogel in combination with stem cells could be a potential therapeutic strategy for ameliorating cardiac repair after significant damage.
Abstract 330: No Direct Mitochondrial Protection Against Ischemia Reperfusion Injury in Rat Isolated Hearts by P188 Postconditioning
Authors: Josephine Eskaf, Luise J Meyer, William J Cleveland, Zhu Li, Matthias L Riess
Journal: Circulation (2020)

Introduction: Myocardial infarction and cardiac arrest lead to ischemia-reperfusion (IR) injury in the heart. Timely reperfusion through percutaneous coronary intervention and cardiopulmonary resuscitation, respectively, reduces ischemia but also exacerbates myocardial injury. Maintaining mitochondrial function is crucial in maintaining cardiomyocyte function in IR injury. Poloxamer 188 (P188) is a triblock copolymer that has shown protective effects in in-vitro, ex-vivo and in-vivo myocardial IR models. P188 is thought to improve cellular and mitochondrial function during IR by stabilizing membranes. Hypothesis: P188 postconditioning has direct protective effects on mitochondrial function as assessed by ATP synthesis, oxygen consumption and calcium retention capacity (CRC). Methods: After approval by the local authorities, hearts of 42 adult male Sprague-Dawley rats were isolated and perfused ex-vivo with oxygenated Krebs Buffer (KB) for 20 min before 30 min of no-flow ischemia. Hearts were reperfused for 10 min with KB. Cardiac mitochondria were isolated with 1 mM P188 vs 1 mM polyethylene glycol (PEG) vs vehicle by differential centrifugation. Mitochondrial function was assessed for complex I and II substrates of the respiratory chain. Statistics: Kruskal-Wallis with Dunn’s posthoc testing; alpha=0.05. Results: Mitochondrial function decreased significantly after ischemia and showed improvement with reperfusion. P188 did not result in significant improvements in mitochondrial ATP synthesis, oxygen consumption and CRC function after IR, and neither did PEG. Conclusions: P188 does not have a direct protective effect on mitochondria in this model. This might be owed to the fact that no additional damage could be observed after reperfusion which is the type of injury targeted by P188 post-conditioning.
Abstract 13499: Percutaneous Coronary Intervention for Bifurcation Lesions in Patients With Acute Coronary Syndrome
Authors: RAHUL CHOUDHARY, Surender Deora, Atul Kaushik, Jai B Sharma
Journal: Circulation (2020)

Introduction: Percutaneous coronary intervention (PCI) for the treatment of bifurcation lesions in acute coronary syndrome (ACS) setting is a high-risk procedure and is associated with higher periprocedural complications and a lower procedural success rate. Hypothesis: We assessed the hypothesis that PCI for bifurcation stenting in ACS is safe and effective as in non ACS condition. Methods: Out of 986 patients who underwent PCI for ACS, 144 (14.6%) patients having bifurcation lesion were included in study. Provisional stenting was favored whenever feasible (86.8%), elective bifurcation stenting (2 stent strategy) was reserved for significant long segment side branch involvement (13.2%). Occurrence of major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis, was observed during follow up. Results: LAD bifurcation was the most common lesion (49.3%), most common Medina class was 1, 1, 1 (52.1%), 70.8% of the procedures were done transradially, angiographic success rate for main vessel was 97.9% and there was no periprocedural mortality or stroke. There was no significant difference regarding risk factors (age, hypertension, diabetes mellitus, dyslipidemia and smoking history; p &gt; 0.05) between 1 stent and 2-stent groups. Median Syntax score was 14(IQR 10-20) in 1 stent group and 22(IQR 17-25) in 2 stent group. The 2-stent group had higher proportion of left main coronary involvement as compared to 1 stent group (47.4 vs 24.8%). Crush was preferred elective 2-stent strategy as compared to TAP in provisional approach (used in 73.7 and 62.5%). Final kissing balloon inflation was used in 38.4% patients in 1- stent group, while it was utilised in all patients with 2- stent approach. Post procedural side branch diameter stenosis (by QCA) differed significantly between the 2 groups (1-stent vs 2-stent, 34.9 vs 6.4%).The rate of MACE was similar in both groups ( total 7 MACE events; median follow-up of 18 months) but radiation dose and contrast volume utilization were significantly more in 2-stent group. Conclusions: PCI for bifurcation lesions had acceptable success and MACE rate even during ACS settings and whenever feasible, provisional stenting should be preferred approach.
Abstract 14970: Normative Echocardiographic Data for Premature Infants Between 23 to 26- and 6/7-weeks Gestational Age
Authors: Nikola Dragisic, Benjamin E REINKING, Griffin geick, Amy Hahn, Jennifer Maldonado, Jonathan Dagle, Regan E Giesinger, Amanda Darnall
Journal: Circulation (2020)

Background: Echocardiography is utilized to assess cardiac structure and function. In infants, children, and adolescents, a normative data set can be utilized to evaluate cardiac size relative to patient body size and provides the clinician with a quantified z-score based on body surface area. A complete normative data set for premature infants is not yet available. The aim of this study was to develop a normative data set for commonly measured cardiac structures in a cohort of premature infants. Methods and Results: Single center retrospective echocardiographic study in a cohort of premature infants without congenital heart disease. A total of 184 infants admitted at the University of Iowa’s Neonatal Intensive Care Unit between 2009-2019 were included in the study. All infants were between 23 to 26- and 6/7-weeks gestational age. We considered patients with a patent ductus arteriosus and/or a patent foramen ovale as having normal intra-cardiac anatomy given their prematurity. Some infants had numerous echocardiograms during this time interval which resulted in 439 utilized echocardiogram. Each echocardiogram used was interpreted individually regardless if the patient had multiple between the gestational ages of 23 and 26- and 6/7-weeks. Commonly examined cardiac structures were assessed via 2-dimensional and M-mode echocardiography. The mean and standard deviations were obtained for each cardiac structure and grouped by week of gestational age ( Table 1 ). Conclusions: We present normative data for commonly measured cardiac structures based on gestational age in a premature patient population. This information is valuable for clinicians to assess for appropriate cardiac structural development and may be utilized to guide clinical management and need for possible intervention as the child continues to develop and grow.
Abstract 15009: Hospital Readmission Among Anticoagulated Nonagenarians With Atrial Fibrillation: A Nationwide Cohort Sample
Authors: Kiro Barssoum, Ahmed Elkaryoni, Adel Muhanna, Islam Shatla, Islam Abdelkarim, Alan P Wimmer
Journal: Circulation (2020)

Background: The prevalence of atrial fibrillation (AF) increases with age, reaching 10% among those above the age of 80. The safety and efficacy of using anticoagulation (AC) to prevent stroke among nonagenarians are not well understood, due underrepresentation of this cohort in landmark clinical trials of oral anticoagulants. We sought to explore readmission rates for all-cause, gastrointestinal bleeding, and acute cerebrovascular events for nonagenarians on AC for AF compared to patients younger than 90. Methods: By using the Nationwide Readmission Database (NRD) from 2010-2015 and ICD-9-CM codes, we identified patients hospitalized with diagnoses of AF and chronic AC, and excluded patients under age 18, those who died during the index admission, and those with pulmonary embolism, deep vein thrombosis or a prosthetic valve. Patients hospitalized in December for each calendar year were excluded to allow 30-day follow-up for all patients since the database resets annually. Chi-Square test was used to compare readmission rates between the two groups and a linear test was used to analyze the trend for AC use across years. Results: Our criteria identified a total of 1,456,114 patients, of whom 132,476 (9.0%) were ≥ 90 years old. Use of AC for AF among nonagenarians increased over the years of the study from 12.3% in 2010 to 22.7% in 2015 (p&lt;0.001). Thirty-day readmission rates in nonagenarians vs. those &lt; 90 were: all-cause - 16.9% vs. 17.2% (p=0.03), gastrointestinal bleeding - 0.5% vs. 0.4% (p&lt;0.001), and acute cerebrovascular events - 0.8% vs. 0.5% (p&lt;0.001). Conclusion: Although the differences were small, nonagenarians treated with AC for AF had a lower 30-day all-cause readmission rate but higher gastrointestinal bleeding and acute cerebrovascular event re-hospitalization rates. Further investigations are warranted to explore the benefit vs. risk of using AC in this vulnerable population of patients.