bluuebunny/crossref_metadata_2025 huggingface dataset:
The PET-Tracer 89Zr-Df-IAB22M2C Enables Monitoring of Intratumoral CD8 T-cell Infiltrates in Tumor-Bearing Humanized Mice after T-cell Bispecific Antibody Treatment
Authors: Griessinger Christoph M. , Olafsen Tove , Mascioni Alessandro , Jiang Ziyue Karen , Zamilpa Charles , Jia Fang , Torgov Michael , Romero Jason M. , Marchioni Filippo , Satpayev Daulet , Lee Chenyu , Zhang Green , Nayak Tapan K. , Pincha Mudita , Amann Maria , Mohan Preethi L.B. , Richard Marine , Nicolini Valeria G. , Sam Johannes , Claus Christina , Ferrara Claudia , Brünker Peter , Bacac Marina , Umana Pablo , Rüttinger Dominik , Wilson Ian A. , Gudas Jean , Klein Christian , Tessier Jean J.L.
Published: May 2020

CD8-expressing T cells are the main effector cells in cancer immunotherapy. Treatment-induced changes in intratumoral CD8+ T cells may represent a biomarker to identify patients responding to cancer immunotherapy. Here, we have used a 89Zr-radiolabeled human CD8-specific minibody (89Zr-Df-IAB22M2C) to monitor CD8+ T-cell tumor infiltrates by PET. The ability of this tracer to quantify CD8+ T-cell tumor infiltrates was evaluated in preclinical studies following single-agent treatment with FOLR1-T-cell bispecific (TCB) antibody and combination therapy of CEA-TCB (RG7802) and CEA-targeted 4-1BB agonist CEA-4-1BBL. In vitro cytotoxicity assays with peripheral blood mononuclear cells and CEA-expressing MKN-45 gastric or FOLR1-expressing HeLa cervical cancer cells confirmed noninterference of the anti-CD8-PET-tracer with the mode of action of CEA-TCB/CEA-4-1BBL and FOLR1-TCB at relevant doses. In vivo, the extent of tumor regression induced by combination treatment with CEA-TCB/CEA-4-1BBL in MKN-45 tumor–bearing humanized mice correlated with intratumoral CD8+ T-cell infiltration. This was detectable by 89Zr-IAB22M2C-PET and γ-counting. Similarly, single-agent treatment with FOLR1-TCB induced strong CD8+ T-cell infiltration in HeLa tumors, where 89Zr-Df-IAB22M2C again was able to detect CD8 tumor infiltrates. CD8-IHC confirmed the PET imaging results. Taken together, the anti-CD8-minibody 89Zr-Df-IAB22M2C revealed a high sensitivity for the detection of intratumoral CD8+ T-cell infiltrates upon either single or combination treatment with TCB antibody–based fusion proteins. These results provide further evidence that the anti-CD8 tracer, which is currently in clinical phase II, is a promising monitoring tool for intratumoral CD8+ T cells in patients treated with cancer immunotherapy.

Significance:

Monitoring the pharmacodynamic activity of cancer immunotherapy with novel molecular imaging tools such as 89Zr-Df-IAB22M2C for PET imaging is of prime importance to identify patients responding early to cancer immunotherapy.
The NKG2A–HLA-E Axis as a Novel Checkpoint in the Tumor Microenvironment
Authors: Borst Linda , van der Burg Sjoerd H. , van Hall Thorbald
Published: May 2020

The success of checkpoint blockade therapy revolutionized cancer treatment. However, we need to increase the fraction of responding patients and overcome acquired resistance to these therapies. Recently, the inhibitory receptor NKG2A received attention as a new kid on the block of immune checkpoints. This receptor is selectively expressed on cytotoxic lymphocytes, including natural killer cells and CD8 T cells, and NKG2A+ T cells are preferentially residing in tissues, like the tumor microenvironment. Its ligand, histocompatibility leucocyte antigen E (HLA-E), is a conserved nonclassical HLA class I molecule that binds a limited peptide repertoire and its expression is commonly detected in human cancer. NKG2A blockade as a standalone therapy appears poorly effective in mouse tumor models, however, in the presence of activated T cells, for example, induced by PD-1/PD-L1 blockade or cancer vaccines, exerts strongly enhanced efficacy. Clinical trials demonstrated safety of the humanized NKG2A-blocking antibody, monalizumab, and first results of phase II trials demonstrate encouraging durable response rates. Further development of this axis is clearly warranted.
High EREG Expression Is Predictive of Better Outcomes in Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy
Authors: Lin Cheng-Yi , Hsieh Pei-Ling , Chou Chia-Lin , Yang Ching-Chieh , Lee Sung-Wei , Tian Yu-Feng , Shiue Yow-Ling , Li Wan-Shan
Published: May 2020

Background/Aim: A great proportion of patients with rectal cancer initially present with locally advanced disease and can potentially benefit from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before surgery. However, risk and clinical outcome stratification remain a great challenge. We aimed to find the potential biomarker to predict the effect of neoadjuvant CCRT on rectal cancer. Methods: We identified epiregulin (EREG) as the most significant predictive marker for neoadjuvant CCRT response from the published rectal cancer transcriptome data set GSE35452. We collected 172 biopsy specimens from rectal cancer patients who received neoadjuvant CCRT followed by radical proctectomy, performed EREG immunohistochemistry, and analyzed the H-scores. We further examined the correlations between the expression level of EREG and clinicopathological features, tumor regression grade, and survival, including disease-specific survival (DSS), locoregional recurrence-free survival (LRFS), and metastasis-free survival (MeFS). Results: High EREG expression was significantly related to early pretreatment (pre-Tx) and posttreatment (post-Tx) tumor status (T1, T2, p = 0.047 and p < 0.001), pre-Tx and post-Tx negative nodal status (N0, p < 0.001 and p = 0.004), less vascular and perineurial invasion (p = 0.015 and p = 0.023), and higher tumor regression grade (p < 0.001). In the survival analysis, high EREG expression was significantly associated with better DSS (p < 0.0001), LRFS (p = 0.0004), and MeFS (p < 0.0001). In the multivariate analysis, high EREG expression remained prognostically significant for better DSS (p = 0.003; hazard ratio: 5.599). Conclusion: These data suggest that EREG is a potential predictive marker and therapeutic target in rectal cancer patients receiving neoadjuvant CCRT.
Hidradenitis Suppurativa: Surgical and Postsurgical Management
Authors: Manfredini Marco , Garbarino Federico , Bigi Laura , Pellacani Giovanni , Magnoni Cristina
Published: May 2020

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Several medical treatments, with varying degrees of efficacy, have been developed. However, in most cases of advanced HS, the definitive treatment option is often represented by surgical excisions. Objective: Surgical techniques, reconstructive approach, and local wound care should be accurately designed in order to obtain the best result. In this review we analyze the possible surgical treatments and local wound care. Methods: A MEDLINE search was performed on the various surgical treatments, reconstructive techniques, and local wound care. Results: Surgical treatment is a common therapeutic modality for HS. Different surgical reconstructive techniques and post-surgical wound care approaches are described for the management of HS patients. Conclusions: There were few high-quality evidence-based studies evaluating the surgical management of HS. Many disparate HS severity scores were used in these studies, making comparisons between them difficult. Nonetheless, research on different surgical approaches and wound care management has increased substantially in the past decade and it has given patients more surgical therapeutic strategies. The description of the best combinations and timing of surgery, wound care, and medical therapies will be a matter of future research for the definition of the optimal management of the HS patient.
Oncology Informatics: Status Quo and Outlook
Authors: Putora Paul Martin , Baudis Michael , Beadle Beth M. , El Naqa Issam , Giordano Frank A. , Nicolay Nils H.
Published: May 2020

Oncology has undergone rapid progress, with emerging developments in areas including cancer stem cells, molecularly targeted therapies, genomic analyses, and individually tailored immunotherapy. These advances have expanded the tools available in the fight against cancer. Some of these have seen broad media coverage resulting in justified public attention. However, these achievements have only been possible due to rapid developments in the expanding field of biomedical informatics and information technology (IT). Artificial intelligence, radiomics, electronic health records, and electronic patient-reported outcome measures (ePROMS) are only a few of the developments enabling further progress in oncology. The promising impact of IT in oncology will only become reality through a multidisciplinary approach to the complex challenges ahead.
Autologous Corneal Transplant from an Enucleated Fellow Eye for Choroidal Melanoma: A Case Report
Authors: Iglicki Matias , Loewenstein Anat , Manera Manuel , Castro Claudia , Busch Catharina , Zur Dinah , Negri Hermino Pablo
Published: May 2020

Background: To report a case of autologous corneal transplant in a patient with corneal leukoma and choroidal melanoma in the fellow eye. Case Presentation: A 56-year-old woman was complaining about decrease in vision in her left eye. The patient was on the waiting list for a corneal transplant on her right eye due to corneal leucoma after a previous herpes infection. The patient was diagnosed with choroidal melanoma in her left eye. Due to the tumor size (longitudinal diameter >10 mm; anterior-posterior diameter >16 mm) the patient decided to undergo enucleation, after being informed about different treatment options (brachytherapy and enucleation). The patient showed her willingness to use the cornea of the left eye as a transplant for her right eye. After discussion with the ethical committee and its approval, and signing informed consent, the patient underwent enucleation of her left eye. The sample was examined by a pathologist and found to be free of melanoma cells in the corneolimbal tissue. Afterwards, trepanation of the donor cornea button was performed and transplanted to the left eye. Conclusion: Autologous corneal transplantation is a safe and feasible procedure in selected cases.
Is Handedness Associated with the Depth of the Olfactory Sulcus?
Authors: Zang Yunpeng , Whitcroft Katie L. , Glöckler Carmina , Hummel Thomas
Published: May 2020

Background: Structural and functional asymmetry is frequent in biological systems. The aim of the present study was to examine whether there is a relation between handedness and the depth of the olfactory sulcus (OS) and reinvestigate whether there is a lateralization of OS depth. Methods: Forty-two healthy volunteers (mean age 24.1 years; 23 right-handed and 19 left-handed) participated. The subjects’ brains were scanned using magnetic resonance imaging to assess OS depth. Normal olfactory function was ascertained using the Sniffin’ Sticks odor identification test. Results: There was no significant difference in OS depth between right- and left-handed participants (right-handed mean: right OS depth = 11.3 mm, left OS = 10.6 mm; left-handed mean: right OS = 11.3 mm, left OS = 11.0 mm). Across all subjects, OS depth was significantly larger on the right side compared to the left. Conclusion: Handedness has no major influence on OS depth. The present study confirmed that the right OS is deeper compared to the left OS, possibly indicating a right-sided lateralization of the olfactory system. Implications: The depth of the right OS is larger than that of the left OS. No major effect of handedness was observed.
Lymphatic and Immune Cell Cross-Talk Regulates Cardiac Recovery After Experimental Myocardial Infarction
Authors: Houssari Mahmoud , Dumesnil Anais , Tardif Virginie , Kivelä Riikka , Pizzinat Nathalie , Boukhalfa Ines , Godefroy David , Schapman Damien , Hemanthakumar Karthik A. , Bizou Mathilde , Henry Jean-Paul , Renet Sylvanie , Riou Gaetan , Rondeaux Julie , Anouar Youssef , Adriouch Sahil , Fraineau Sylvain , Alitalo Kari , Richard Vincent , Mulder Paul , Brakenhielm Ebba
Published: May 2020

Objective:

Lymphatics play an essential pathophysiological role in promoting fluid and immune cell tissue clearance. Conversely, immune cells may influence lymphatic function and remodeling. Recently, cardiac lymphangiogenesis has been proposed as a therapeutic target to prevent heart failure after myocardial infarction (MI). We investigated the effects of gene therapy to modulate cardiac lymphangiogenesis post-MI in rodents. Second, we determined the impact of cardiac-infiltrating T cells on lymphatic remodeling in the heart.

Approach and Results:

Comparing adenoviral versus adeno-associated viral gene delivery in mice, we found that only sustained VEGF (vascular endothelial growth factor)-C
C156S
therapy, achieved by adeno-associated viral vectors, increased cardiac lymphangiogenesis, and led to reduced cardiac inflammation and dysfunction by 3 weeks post-MI. Conversely, inhibition of VEGF-C/-D signaling, through adeno-associated viral delivery of soluble VEGFR3 (vascular endothelial growth factor receptor 3), limited infarct lymphangiogenesis. Unexpectedly, this treatment improved cardiac function post-MI in both mice and rats, linked to reduced infarct thinning due to acute suppression of T-cell infiltration. Finally, using pharmacological, genetic, and antibody-mediated prevention of cardiac T-cell recruitment in mice, we discovered that both CD4
+
and CD8
+
T cells potently suppress, in part through interferon-γ, cardiac lymphangiogenesis post-MI.

Conclusions:

We show that resolution of cardiac inflammation after MI may be accelerated by therapeutic lymphangiogenesis based on adeno-associated viral gene delivery of VEGF-C
C156S
. Conversely, our work uncovers a major negative role of cardiac-recruited T cells on lymphatic remodeling. Our results give new insight into the interconnection between immune cells and lymphatics in orchestration of cardiac repair after injury.
Relative Costs of Surgical and Transcatheter Aortic Valve Replacement and Medical Therapy
Authors: Goldsweig Andrew M. , Tak Hyo Jung , Chen Li-Wu , Aronow Herbert D. , Shah Binita , Kolte Dhaval , Desai Nihar R. , Szerlip Molly , Velagapudi Poonam , Abbott J. Dawn
Published: May 2020

Background:

The number of patients treated for aortic valve disease in the United States is increasing rapidly. Transcatheter aortic valve replacement (TAVR) is supplanting surgical aortic valve replacement (SAVR) and medical therapy (MT). The economic implications of these trends are unknown. Therefore, we undertook to determine the costs, inpatient days, and number of admissions associated with treating aortic valve disease with SAVR, TAVR, or MT.

Methods:

Using the Nationwide Readmissions Database, we identified patients with aortic valve disease admitted 2012 to 2016 for SAVR, TAVR, and disease symptoms (congestive heart failure, unstable angina, non–ST-elevation myocardial infarction, syncope). Patients not undergoing SAVR or TAVR were classified as receiving MT. Beginning with the index admission, we estimated inpatient costs, days, and admissions over 6 months.

Results:

Among 190 563 patients with aortic valve disease, the average aggregate 6-month inpatient costs were $59 743 for SAVR, $64 395 for TAVR, and $23 460 for MT. Mean index admission was longer for SAVR (10.0 days) than for TAVR (7.0 day) or MT (5.3 days), but the average number of unplanned readmission inpatient days was 2.0 for SAVR, 3.0 for TAVR, and 4.3 for MT; the average number of total admissions was 1.3 for SAVR, 1.5 for TAVR, and 1.7 for MT (
P
<0.01 for all). TAVR index admission costs decreased over time to become similar to SAVR costs by 2016.

Conclusions:

Aggregate costs were higher for TAVR than SAVR and were significantly more expensive than MT alone. However, TAVR costs decreased over time while SAVR and MT costs remained unchanged.
Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier Integrity
Authors: Veys Koen , Fan Zheng , Ghobrial Moheb , Bouché Ann , García-Caballero Melissa , Vriens Kim , Conchinha Nadine Vasconcelos , Seuwen Aline , Schlegel Felix , Gorski Tatiane , Crabbé Melissa , Gilardoni Paola , Ardicoglu Raphaela , Schaffenrath Johanna , Casteels Cindy , De Smet Gino , Smolders Ilse , Van Laere Koen , Abel E. Dale , Fendt Sarah-Maria , Schroeter Aileen , Kalucka Joanna , Cantelmo Anna Rita , Wälchli Thomas , Keller Annika , Carmeliet Peter , De Bock Katrien
Published: May 2020

Rationale:

Endothelial cells (ECs) are highly glycolytic and generate the majority of their energy via the breakdown of glucose to lactate. At the same time, a main role of ECs is to allow the transport of glucose to the surrounding tissues. GLUT1 (glucose transporter isoform 1/
Slc2a1
) is highly expressed in ECs of the central nervous system (CNS) and is often implicated in blood-brain barrier (BBB) dysfunction, but whether and how GLUT1 controls EC metabolism and function is poorly understood.

Objective:

We evaluated the role of GLUT1 in endothelial metabolism and function during postnatal CNS development as well as at the adult BBB.

Methods and Results:

Inhibition of GLUT1 decreases EC glucose uptake and glycolysis, leading to energy depletion and the activation of the cellular energy sensor AMPK (AMP-activated protein kinase), and decreases EC proliferation without affecting migration. Deletion of GLUT1 from the developing postnatal retinal endothelium reduces retinal EC proliferation and lowers vascular outgrowth, without affecting the number of tip cells. In contrast, in the brain, we observed a lower number of tip cells in addition to reduced brain EC proliferation, indicating that within the CNS, organotypic differences in EC metabolism exist. Interestingly, when ECs become quiescent, endothelial glycolysis is repressed, and GLUT1 expression increases in a Notch-dependent fashion. GLUT1 deletion from quiescent adult ECs leads to severe seizures, accompanied by neuronal loss and CNS inflammation. Strikingly, this does not coincide with BBB leakiness, altered expression of genes crucial for BBB barrier functioning nor reduced vascular function. Instead, we found a selective activation of inflammatory and extracellular matrix related gene sets.

Conclusions:

GLUT1 is the main glucose transporter in ECs and becomes uncoupled from glycolysis during quiescence in a Notch-dependent manner. It is crucial for developmental CNS angiogenesis and adult CNS homeostasis but does not affect BBB barrier function.
Abstract 106: Circulating Immune Cells as Predictive Markers of Cardiovascular Mortality in Ambulatory US Adults: Insights From NHANES
Authors: Gupta Kartik , Nagalli Shivaraj , Pate Mike , Gharpure Nitin , Prabhu Sumanth , Bajaj Navkaranbir S
Published: May 2020

Introduction:
While inflammation is associated with worse cardiovascular (CV) prognosis, the relative prognostic importance of circulating immune cell populations for predicting CV mortality is unknown.

Methods:
We used data from 3 cycles of NHANES (1999-2000, 2001-2002, 2003-2004) to estimate the prognostic importance of total leukocyte count (TLC), and differential leukocyte counts in participants ≥20 years of age and TLC in normal clinical range (4,000-11,000 cells/μL). The cause of death was derived from the National Death Index. We estimated the relative importance of different immune cell markers, and compared the prognostic importance of the dominant immune cell marker with components of the Framingham Risk Score (FRS). We used partial χ2 and standardized domination statistic to estimate the relative importance of immune markers in predicting CV mortality.

Results:
Among 10, 825 participants (49% women, 51% self-reported Non-Hispanic White) eligible for this analysis, the median age was 49 years (Interquartile Range [IQR] 35 to 66). Over a median follow-up of 13.2 years (IQR 11.4 to 14.8), there were 620 deaths due to CV causes. The hazard of CV mortality increased by 11% with every 1000 cells/uL increase in TLC after adjusting for co-morbidities (Hazard Ratio [HR] 1.11 95% CI 1.02, 1.21, p=0.011). Among the immune cell markers assessed, the monocyte-lymphocyte ratio had the highest domination to predict CV mortality (
Figure Panel A
). The hazard of CV mortality increased by 14% with every 1 unit increase in the monocyte-lymphocyte ratio in the fully adjusted model (HR 1.14 95% CI 1.07, 1.22, p<0.001). Among participants aged ≥30 years without prevalent CV disease, FRS was calculated in 8,190 participants (75.7% of total). As compared to the individual components of FRS, the monocyte-lymphocyte ratio had higher relative importance in predicting CV mortality than gender, smoking status, HDL, total cholesterol and treatment for hypertension (
Figure Panel B
).

Conclusion:
In this study of a large representative adult US population with TLC within the clinically normal range, we found that readily available circulating immune markers are independently associated with CV mortality. The monocyte-lymphocyte ratio was the best predictor of CV mortality and outperformed 5 risk factors included in the FRS.
Abstract 109: Reducing False Alarms in Intensive Care Units: A Generalizable Approach Based on Convolutional Neural Networks
Authors: Bollepalli Sandeep Chandra , Joseph Stigi , Jana Soumya
Published: May 2020

Background:
At intensive care units (ICUs), multiple physiological signals are continuously monitored so as to detect the onset of critical health events and generate alarms. In current systems, most such alarms happen to be false and correspond to innocuous events such as muscle movement or electrical disconnection. High rate of such false alarms (FAs) undesirably reduces staff responsiveness and annoys patients. Indeed, reducing the harm associated with clinical alarm systems is listed as a national patient safety goal of 2019.

Objective:
We seek to reduce FA rate in ICUs, while preserving true alarms, by collating information from interdependent vital signals including electrocardiogram, photoplethysmogram and arterial blood pressure signals. In this regard, we propose an approach that generalizes to various arrhythmic conditions, and hence simplifies design.

Methods:
We propose FARIC, a method of False Alarm Reduction in ICU based on Convolutional neural network (CNN). In particular, we use CNNs as building blocks (see Figure) to glean the heartbeat location and morphology information from multiple physiological signals by suitably modifying the training data. Here, as the features are algorithmically learnt from the example waveforms, we eliminate the need for handcrafted signal-specific and arrhythmia-specific features, thus making our method generalizable.

Results:
We evaluated FARIC on the PhysioNet/CinC 2015 Challenge dataset, consisting of 1250 patient records collected at four hospitals in the USA and Europe. Our model was trained on the 750 public records, and tested on all records including 500 hidden ones. The Challenge at hand compares the efficacy of competing techniques in reducing ICU FA rate using a standardized score that penalizes false negatives heavily. Alongside an overall score, individual score was given for each of the following arrhythmias: Asystole, Extreme Bradycardia, Extreme Tachycardia, Ventricular Tachycardia and Ventricular Fibrillation/Flutter. Encouragingly, FARIC either matched or exceeded each of hitherto leading arrhythmia-specific scores and added more than 4 percent points to the leading overall score (see Table).

Conclusion:
Our method promises to significantly reduce the FA rate in ICUs, and can be extended to additional arrhythmic conditions.
Abstract 17: Social Determinants of Health and Participant Retention in a Disparities Study and Primary Care: Findings From the Hypertension and Values (hyvalue) Trial
Authors: Henderson Kamal , Helmkamp Laura , Hanratty Rebecca , Miriam Dickinson , Havranek Edward , Julie Maertens , Blair Irene , Daugherty Stacie L
Published: May 2020

Background:
Clinical research has long suffered from a lack of research participants of diverse backgrounds, such as racial-ethnic minorities and women. How social determinants of health (SDOH) influence retention of research participants in clinical trials has not been well studied. Among a population of patients from three diverse health systems who enrolled in a prospective trial testing a psychosocial intervention, values affirmation, on racial disparities in hypertension medication adherence, we assessed whether SDOH were associated with study retention over 6 months.

Methods:
Adults who self-identified as non-Hispanic White or Black/African American, had uncontrolled hypertension and enrolled in the Hypertension and Values (HYVALUE) trial from January 2016 through June 2019 were included. Measures of high SDOH burden included: 1) self-reported low-education attainment (high school diploma or equivalent or less than a high school education), 2) difficulty paying for basics (individuals that reported it was hard to pay for the basics like food, housing, medical care, and heating), OR 3) social isolation (unmarried or lived alone). Poor study retention was defined as not completing at least one of the 3- or 6-month follow-up visits. Log binomial regression models adjusting for age, gender, and race-ethnicity were used to estimate the probability of study retention associated with 1 or more SDOH factors.

Results:
Among 814 study participants, the mean age was 63 years (standard deviation, 11.7 years), 59.1% were women, 51.2% were African-American, and 68.6% had at least one SDOH factor. Overall, 78.1% of participants completed at least one follow-up study visit. African-American participants, women, and individuals with public insurance (i.e., Medicare and/or Medicaid) were more likely to have at least one SDOH factor (72.4% of AAs vs 64.5% of white, 71.1% of women vs 64.5% of men, and 75.2% of those with public insurance vs 53.9% with commercial, respectively). Participants with at least one SDOH factor were less likely to have to have completed a follow-up visit compared to those with no SDOH (75.1% vs 84.8%,
p
=0.002). When adjusted for age, gender and race-ethnicity, those with at least one SDOH remained significantly less likely to have completed a follow-up visit (adjusted RR 0.91, 95% CI 0.85-0.97).

Conclusions:
In an ongoing prospective trial evaluating the impact of a Values Affirmation intervention on hypertension medication adherence, we found that a higher burden of SDOH was associated with poorer study retention independent of age, gender or race. Our study suggests that trials with diverse populations should consider retention plans that are attentive to challenges of socially disadvantaged participants.
Abstract 204: Impact of Global Budgets on Hospital Cardiovascular Care in Maryland
Authors: Viganego Federico , Friebel Rocco , Um Ann E , Ruffin Jasmine , Fradley Michael , Prida Xavier
Published: May 2020

Background:
Global budgets (GB), an innovative method of hospital payment, have been considered effective in containing expenditures. In January 2014, the state of Maryland introduced Global Budget Revenues (GBR), transitioning from
per case
to capitated, population-based payments (PBP). Under this model, hospitals are provided yearly funds, thus being financially incentivized to improve efficiency of services. Prices are set by the Health Services Cost Review Commission (HSCRC), which collects data and monitors hospitals’ quality of care. Potential adverse incentives of GB would include underprovision of necessary services or avoiding sicker, high cost patients (cream skimming). This study aimed to evaluate the effects of GBR on the care of hospitalized patients with important CV conditions.

Methods:
We analyzed HSCRC inpatient claim databases containing anonymized information on statewide hospital admissions between fiscal years 2013 and 2018. Using ICD codes, we identified patients with a principal diagnosis of heart failure (CHF), acute myocardial infarction (AMI), and acute ischemic stroke (AIS) from a pool of 1,959,237 inpatient admissions. Outcome measures were: hospitalizations, length of stay (LOS), inpatient PCI and CABG procedure rates, casemix adjusted 30-day readmission rates (CARR), risk standardized in-hospital mortality, and hospitalization charges. Trends in outcome measures before and after GBR implementation were compared using segmented regression analysis, with p values indicating trend change.

Results:
With introduction of GBR, CHF and AMI hospitalization trends did not change significantly, whereas AIS admissions stabilized downward (p<0.0001). There was an increase in mean LOS for CHF (p=0.059). CARR followed pre-policy declining trends, with more consistent improvements noted for the AMI cohort (p=0.005). In-hospital mortality continued to decrease, although at slower rates for CHF and AMI cohorts (p=0.03; p=0.019). CABG procedure rates declined significantly (p<0.0001). Mean hospitalization charges increased for all three CV conditions, faster for CHF (p=0.03) and AIS (p<0.0001), slower for AMI (p=0.0003).

Conclusions:
Adoption of GBR in Maryland had no harmful effects on in-hospital outcomes and quality measures. There was a modest improvement in potentially avoidable hospitalizations and mildly reduced utilization offset by significant rise in charges. Some observations could result from care shifts to the outpatient setting. Quality of CV care was not affected by GBR suggesting that efficiency improvements might have occurred in other areas of the healthcare system. Additionally, combining GB with pay for performance programs and assiduous quality monitoring might have mitigated adverse incentives. As GBR transitions to Maryland Total Cost of Care, long-term effects of PBP on CV outcomes will require further investigation.
Abstract 211: Association of Bariatric Surgery With Major Adverse Cardiovascular Outcomes: Insights From the National Inpatient Sample 2012-2016
Authors: Nguyen Tran , Alzahrani Talal , Krepp Joseph
Published: May 2020

Background:
Approximately one in every three people in the United States has obesity. There is a strong association between obesity and an increased rate of cardiovascular disease (CVD)-related mortality. Bariatric surgery (BS) refers to a variety of procedures performed to achieve a reduction of excess weight. Many small randomized controlled trials and observational studies have demonstrated the association between BS and reduction in major adverse cardiac events (MACEs) among patients with obesity and Type 2 diabetes. However, these studies have been limited by small sample sizes, localized database, or inclusion of surgical procedures no longer commonly used. Our study aims to explore the relationship between BS and inpatients MACEs among obese inpatients in the United States, using a large and contemporary national database.

Methods:
This is a retrospective study using the National Inpatient Sample between 2012 and 2016. Adult obese patients with BMI ≥35 (ICD 9/10 codes V85.35, V85.4x/ Z68.35, Z68.4x) were included (n= 1,700, 943). First, a univariate analysis was performed to study differences in clinical characteristics between obese patients with BS status (identified by ICD9/10 codes V45.86 / Z98.84, respectively) versus obese patients without BS status. A logistic regression model was then constructed to study the association between undergoing BS and having MACEs, including all-cause mortality, cardiac arrest, acute heart failure, acute myocardial infarction (MI), and cerebrovascular accident after adjusting for CVD risk factors such as gender, diabetes, hypertension, hyperlipidemia, prior MI, chronic kidney disease, atrial fibrillation, and smoking.

Results:
Among 50, 296 patients with BS (2.96%), the mean age was 53 ± 12 years; the majority was female (75.32%), Caucasian (71.85%) and from the hospital region of the South (33.73%). 33.92% had diabetes, 53.27% had hypertension, and 29.60% had hyperlipidemia. Multivariable analysis revealed that obese patients with BS status had a 1.6-fold decrease in the rate of MACEs compared to patients without BS (odds ratio, 0.623; 95% CI, 0.598-0.649; P<0.001).

Conclusion:
The study illustrated that among obese patients with BMI ≥35, a history of bariatric surgery was associated with a statistically significant lower risk of inpatient MACEs, after adjusting for CVD risk factors.
Abstract 212: The Association of Sleep Apnea With 1-year Health Status Outcomes in Patients With Peripheral Artery Disease
Authors: Jelani Qurat-ul-ain , Mena-hurtado Carlos , Gosch Kensey , Mohammed Moghniuddin , Nagpal Sameer , Spertus John , Smolderen Kim G
Published: May 2020

Background:
Comorbid sleep apnea in cardiovascular disease is a predictor of adverse cardiovascular outcomes. It is unknown whether comorbid sleep apnea in PAD is associated with worse PAD-specific health status outcomes.

Methods:
PORTRAIT is an international (US, Netherlands, Australia), 16-center, prospective PAD registry. Health status was assessed upon PAD diagnosis and at 12 months (disease-specific Peripheral Artery Questionnaire, PAQ Summary scores). Higher PAQ scores indicate better health status. A sequentially adjusted hierarchical linear regression model examined the association between sleep apnea and 1-year PAQ scores (figure).

Results:
Of the 1204 patients with PAD, 8.3% (n=100) had comorbid sleep apnea. The mean age was 67.6 ± 9.4 with 37.5% women. Patients with vs. without sleep apnea were more from the US; more sedentary, presented with more diabetes, obesity, coronary disease and a history of peripheral interventions, but had higher ankle-brachial index values. They also had lower health status scores at presentation and 12 months (41.2 ± 22.0 vs 49.9±21.6 and 58.6±27.9 vs71.3±24.9, respectively, p<0.05). The association between sleep apnea and 1-year health status persisted after adjustment (Figure).

Conclusion:
In patients presenting with PAD, comorbid sleep apnea clusters with an overall toxic cardiovascular risk profile. Independent of these risk factors, patients with PAD and sleep apnea obtain less favorable PAD-specific 1-year PAD-specific health status outcomes.

Figure:
The Association Between Sleep Apnea and 1-Year PAQ Summary Scores Following Sequential Adjustment for Demographics, Socioeconomic Factors, PAD severity, Psychosocial Factors and Baseline Health Status Score. Estimates represent Beta coefficients and 95% confidence intervals.
Abstract 224: Implementation of an Actionable EHR-based Population Health Dashboard and Curriculum in a Cardiovascular Disease Fellowship
Authors: Karpenshif Yoav , Boedec Chris , Goldberg Lee R , Silvestry Frank , Myers Jennifer , Adusumalli Srinath
Published: May 2020

Background:
The advent of learning healthcare systems requires physicians to not only manage individual patients, but also use data to manage their patient population as a whole. Improving care using data has been facilitated via the adoption of the EHR and its ability to collate data for populations of patients. While incorporation of population health into residency curricula has become more common, there have been few educational initiatives for fellows despite the requirements of the ACGME that fellowship programs provide trainees with practice habit data relevant to their patient population. We aimed to create and evaluate an ambulatory cardiovascular disease fellowship population health dashboard and curriculum incorporating actionable, relevant metrics.

Methods:
In 2018 we developed a curriculum that taught principles of population health through didactics and videos that CVM fellows in our program could access asynchronously. In parallel, we developed a novel fellow-specific population health dashboard embedded in our EHR. The dashboard included demographic information relating to the fellow’s clinic patient population such as race/ethnicity, healthcare utilization information like percentage of no-show visits, and specialty specific quality metrics such as beta-blocker use in patients with CHF. CVM fellows (PGY4-7) participated in the effort. Fellows were encouraged to review their practices then coached by a CVM faculty member in one-to-one sessions to develop strategies to improve one or more quality metrics of their choice. Pre and post surveys were administered to determine baseline and post-curriculum knowledge, attitudes, and experience with the topic of population health. We tracked fellow engagement through measured dashboard utilization.

Results:
Pre and post survey response rate was 81% and 46% respectively. At baseline, 23.5% (8) of fellows reported never receiving any education in population health and 67.6% (23) of fellows reported previous experience with population health tools such as EHR dashboards. Only 14.7% (5) of fellows had baseline knowledge of how quality metrics affect health care reimbursement. After the initial year of the curriculum and dashboard implementation, 100% (11) of fellows responding believed that it was important to learn about population health management and planned to utilize the skills they learned in practice. Further, 72% (8) of fellows changed one or more aspects of their practice after utilizing the dashboard coupled with one-on-one coaching. Since EHR dashboard implementation, fellows have accessed the dashboard 560 times.

Discussion:
Integrating population health education utilizing a fellow-specific EHR dashboard in a CVM fellowship is both feasible and highly rated. This method of population health education is scalable across other cardiovascular disease fellowship programs and other subspecialties.
Abstract 225: Impact of Revascularization Strategy on Risk of Readmission After Non-ST Elevation Myocardial Infarction
Authors: Nair Raunak , Johnson Michael , Kravitz Kathleen A , Anabila Moses , Rajeswaran Jeevanantham , Blackstone Eugene H , Menon Venu , Lincoff A Michael M , Kapadia Samir R , Khot Umesh
Published: May 2020

Background:
It is unclear how revascularization strategy (medical management vs percutaneous coronary intervention vs coronary artery bypass surgery), affects 90-day readmissions after Non-ST Elevation Myocardial Infarction (NSTEMI).

Methods:
We identified cases of NSTEMI at a single quaternary care medical center between January 1
st
, 2010 to January 1
st
, 2017 and readmissions within 90 days. Cases were categorized based on revascularization strategy into medical management, PCI (percutaneous coronary intervention) or CABG (coronary artery bypass surgery). The readmissions were categorized according to the time of readmission into early (0-30 days) and late (31-90 days) after discharge. The instantaneous risk of readmission following each treatment option was calculated using the parametric method.

Results:
We identified 6626 patients with index MI, of which 4692 patients had NSTEMI. There were a total of 2051 readmissions within 90 days. The risk of readmission for CABG and PCI treatment groups yielded an early peaking phase followed by a constant risk whereas the risk of readmission in the medically managed group showed an early decreasing phase followed by a constant risk. An unadjusted comparison of the risk of readmission between the three groups showed that the PCI group had the lowest early risk of readmission (P=0.03). The medically managed group had the highest risk of readmission.

Conclusion:
Patients with NSTEMI who are medically managed appear to be at higher risk for readmission than revascularized patients. Understanding the care processes for these patients may serve as a future opportunity to improve outcomes in these high-risk patients.
Abstract 24: Health Status Differences Between Early Invasive and Non Invasive Treatment Strategies in Patients With Peripheral Artery Disease: Insights From Portrait Registry
Authors: Angraal Suveen , Hejjaji Vittal , Derbas Laith , Patel Manesh R , Heyligers Jan , White Christopher J , Tutein Nolthenius Rudolf , Mena-hurtado Carlos , Aronow Herbert D , Hiatt William R , Moneta Gregory L , Fitridge Robert , Soukas Peter , Abbott Jinnette D , Spertus John , Smolderen Kim G
Published: May 2020

Background:
In patients with symptomatic peripheral artery disease (PAD), a key treatment goal is to improve their health status; their symptoms, function, and quality of life (QoL). While medical therapy with lifestyle changes is recommended in all, revascularization can be a consideration to alleviate PAD symptoms. We sought to compare the real-world impact of either treatment strategy on patients’ health status improvement.

Methods:
Patients with new or worsening PAD symptoms (Rutherford category 1-3), from 10 U.S. specialty vascular clinics between 2011-2015, who either underwent early revascularization (using stent, angioplasty or surgery within 3 months of enrolment) or medical management alone (statin, aspirin, cilostazol, supervised exercise therapy, risk factor (diabetes, hypertension) management) were identified from the Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) registry. The Peripheral Artery Questionnaire (PAQ) was used to assess patients’ disease-specific health status at enrollment and at 3, 6 and 12 months of follow up. The differences in PAQ overall summary scores, and each subdomain, were compared using an adjusted generalized linear model for repeated measures (Figure 1).

Results:
Among 797 patients (mean age of 68.6 years, 58.1% male), 226 underwent early revascularization and 571 were managed medically. At baseline, patients in the revascularization vs. medical management cohort had lower PAQ summary scores (mean ± SD; 42.6 ± 20.7 vs. 48.5 ± 22.3, P<0.001) and QoL scores (43.4 ± 23.9 vs. 50.4 ± 26.4, P<0.001). Over 1 year of follow-up, patients who underwent revascularization reported significantly higher health status over time than patients managed medically without revascularization (P <0.001 for all PAQ sub-domains; Figure 1).

Conclusion:
Patients with PAD who received early revascularization had worse health status at baseline, but they reported a greater degree of improvement over 1 year of follow-up when compared to patients managed medically without revascularization. Summarizing real-world health status benefits following a PAD diagnosis is critical to help guide preference-sensitive decisions on PAD management.
Abstract 243: Long-term Effects of ACC/AHA Cholesterol Control on Cardiac Function
Authors: Zhang Jian , Liu Wentao , Chen Yilong , Li Xiangkui , Chen Wei , Li Xin , Li Dong
Published: May 2020

Background:
The impact of long term strict cholesterol control on reservoir function and outcome in heart failure is unclear.

Methods:
We retrospectively analyzed 2939 patients (31.9% female, mean age 65.1±11.8 years) whom strict application of ACC/AHA cholesterol management with an average length of 9.4 years of follow-up. We also evaluated the ventricular ejection fraction, mass, and Global sore (Framingham-CVD), as well as 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk score.

Results:
Overall, 64.3% of patients were identified as strictly cholesterol control (case group). As compared to age-gender-race matched control group, patients in cases group have higher LV mass (152.9±34.4g vs. 143.6±34.4 g, p=0.0005) as well as an LV mass index (90.5±18.1 vs. 85 ±17 g/m2 vs. g/m2, P=0.0002) and Framingham Global CVD Risk score (18.9±17.7 vs. 8.6±17.3, P<0.001), but not for LVEF (68.5%±7.5% vs. 69.1%±6.6%, p=0.263). The average percentage decrease in LVEF in patients with mild coronary artery calcification (CAC score<100) in cases is 6.2%, and when CAC score>400, the LVEF decreased up to 15.3% regardless of the cholesterol control status. Major coronary arteries with severe calcification are associated with increasing the risk of abnormal ejection fraction (LVEF<50%) 4.84 times after adjusting for traditional CAD risk factors. Long-term ACC/AHA cholesterol control can not prevent the ASCVD risk score increase (Table 1).

Conclusions:
The strict long-term application of ACC/AHA cholesterol control can effectively LV mass change. However, this strategy does not adequately prevent LV systolic function attenuation. The 10-Year ASCVD risk score is one of the robust indicators of cardiac function for long-term lipid control outcomes.

Abbreviations:
LAD: left anterior descending, LCX: circumflex coronary arteries, RCA: right coronary artery. CTA: coronary computed tomography angiogram. LVEF:Left Ventricular Ejection Fraction
Abstract 265: A Literature Review of the Direct Medical Costs of Stroke Across the Care Continuum in the US
Authors: Ye Zhiqiu , Ritchey Matthew , MacLeod Kara , Wang Guijing
Published: May 2020

Background:
The economic burden of stroke is high and expected to increase with the growing stroke incidence among younger adults and the aging population. However, we are unaware of a comprehensive review of the cost drivers across the stroke care continuum. We conducted a literature review and summarized the costs incurred in the inpatient and outpatient settings during the acute and post-acute periods.

Methods:
A systematic search of MEDLINE, EMBASE, CINAHL was conducted to identify cost-of-illness studies published during January 2000-October 2019 that evaluated the direct medical costs of stroke in the US. We extracted both the index hospitalization costs and the costs incurred thereafter. We summarized the costs by stroke type (ischemic, intracerebral hemorrhage, subarachnoid hemorrhage, transient ischemic attack) and by cost component (e.g., inpatient hospital stays, skilled nursing facility for rehabilitation, physician consultation, medication use). Cost estimates were adjusted to 2019 dollars by using the US Consumer Price Index.

Results:
Thirty-six studies were included. Thirteen studies (36%) focused on inpatient costs only, twenty-one (58%) estimated both inpatient and outpatient costs, two (6%) examined outpatient costs only. Nine studies (25%) estimated the stroke-attributable costs by using propensity score matching and econometric models. The index hospitalization costed $9,050-$74,525 per admission for ischemic stroke (15 studies), $18,554-$117,991 for hemorrhagic stroke (5 studies), and $9,658-$10,544 for transient ischemic attack (2 studies). Among studies that examined costs beyond the index hospitalization (n=22, 61%), follow-up periods varied from 30 days to 4 years. Sixteen of these studies (73%) estimated total costs only; five (23%) identified costs by period. For ischemic stroke, the total cumulative post-stroke costs were estimated at $15,037 (30-day period), $17,968-$29,704 (90-day), $27,072-$37,611 (180-day), $21,642-$87,135 (1-year), $50,153-$117,683 (2-year), and $70,513-$173,904 (4-year); the proportion attributed to inpatient care reduced from 65% (30-day period) to 46% (4-year). Skilled nursing facility care accounted for 19% of the costs four years post ischemic stroke and for 13% four years post intracerebral hemorrhage stroke. For subarachnoid hemorrhage stroke, inpatient care remained the biggest cost driver four years after the index event (70% of the total cost), followed by outpatient physician services (11%) and skilled nursing facility care (8%).

Conclusions:
While caution should be taken when interpreting the cost findings due to variation in data sources, study population and analytical methods, the costs of stroke are substantial. Inpatient, skilled nursing facility and outpatient physician costs are the main cost drivers and their contribution to total costs vary greatly over time and by stroke type.