tbuckley/cabot-search huggingface dataset:
Abstract 208: MicroRNA 122 and 300 as a Potential Prognosticator of Brain, Kidney and Liver Damage in Response to Ischemic-reperfusion Injury After Severe Rodent Cardiac Arrest
Authors: Rishabh Choudhary, Shabirul Haque, Muhammad Shoaib, Tai Yin, Lance B Becker
Journal: Circulation (2020)

Introduction: Cardiac arrest (CA) causes ischemia and reperfusion damage to the entire body. Augmented expression of circulating microRNA (miR)-122 has been associated with poor neurological outcome after CA, as well as drug and alcohol-induced liver injury in human. Plasma exosomal miR-300 has shown to be up regulated in transient ischemic attack while cellular miR-300 expression increased after traumatic brain injury in rodent model. Hypothesis: The response of tissue injury can be determined by measuring differential expression of miR. This study sought to quantify two specific miR-122 and 300, from the intracellular compartment of the brain, kidney, and liver tissues to determine the injury pattern after severe CA and resuscitation. Methods: Male Sprague-Dawley rats were assigned into 2 groups: control (no CA or CA and resuscitation) and 20 min CA followed by 30 min cardiopulmonary bypass (CPB) resuscitation (n=3). Brain, kidney, and liver tissues were isolated and homogenized. Total RNA was isolated from homogenized tissue by trizol method, RNA was then converted to cDNA by RT kit and processed for miR-122 and miR-300 quantification using quantitative real-time polymerase chain reaction (qRT-PCR). RNU6 was used as an endogenous control and results were expressed in fold change. Results: Brain after CA and resuscitation revealed an increased trend in expression of miR-122 (p=0.053) and miR-300 (p=0.57). Liver also demonstrated an increasing trend in miR-122 (p=0.15) and miR-300 (p=0.007) expression. The increasing trend of miR-122 and miR-300 expression in brain and liver following CA and resuscitation suggests reperfusion injury in the early phase of resuscitation. Kidney demonstrated a lower expression of both miR-122 and miR-300 after CA and resuscitation, which suggests that the event of CA and resuscitation further down regulate miR-122 and miR-300 expression. Conclusion: Levels of intracellular miR-122 and 300 in the brain, kidney, and liver appear to be altered after CA and resuscitation. Although, only one of the miR showed a significant difference in our small exploratory study, the current finding suggests that tissue specific miR levels may provide insight about specific injury following CA.
Abstract 16871: Hypertensive Diseases of Pregnancy Are Associated With Longer Delivery Stays and Rehospitalizations
Authors: Kathryn J Lindley, Kristine Huang, Nicole El Helou, Karen E Joynt Maddox, Molly Stout
Journal: Circulation (2020)

Introduction: Hypertensive diseases of pregnancy (HDP) are common, and are associated with significant short- and long-term cardiovascular morbidity and mortality, but less is known about their association with post-delivery health care utilization. We sought to assess the association of HDP with 90-day post-delivery unplanned hospital revisits (ED visits, observation stays, and readmissions) in a broad cohort of pregnant women. Methods: Retrospective cohort study. Women who delivered from 1/1/2019-12/31/2019 at a large urban hospital were identified using diagnosis related groups. Women with HDP, including eclampsia, preeclampsia, and gestational hypertension were identified using standard ICD-10-CM codes. Logistic regression, controlling for 29 Elixhauser comorbidities including lung disease, obesity, depression, drug use, thyroid disease, renal disease, and others, was used to determine the independent association of HDP with unplanned hospital revisits. Results: Out of 3,391 deliveries, 1,225 (36.1%) mothers had HDP. Women with HDP were of similar age and insurance status as those without, but had higher rates of chronic lung disease (19.4% versus 13.5%), obesity (22.7% versus 7.8%), depression (15.8% versus 11.0%), and drug use (13.8% versus 9.9%, p for all &lt;0.001). Mothers with HDP had longer lengths of stay for their delivery visits (4.7 vs. 3.5 days, p&lt;0.001), and a higher percentage had 1 or more 90-day hospital revisits (42.4% versus 33.1%, p&lt;0.001) than those without HDP. After controlling for comorbidities and insurance coverage, hypertensive disease remained independently associated with 90-day unplanned hospital revisits (odds ratio 1.24, 95% CI [1.06, 1.45], p=0.007). Conclusions: HDP is associated with a high rate of underlying chronic disease and contributes to excess delivery hospitalization days and rehospitalization rates. Novel strategies are required to optimize post-partum care and inter-pregnancy health for this common condition.
Scalp Eruption in a Patient With Metastatic Colon Cancer
Authors: Joseph Zikry, Brandon L. Adler
Journal: JAMA Oncology (2020)

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Abstract 13208: Pedal Arterial Calcification Score Correlates With Risk of Death and Major Adverse Cardiovascular Event in Patients With Chronic Limb Threatening Ischemia
Authors: Iris H Liu, Bian Wu, Viktoriya Krepkiy, roberto ferraresi, Alexander Reyzelman, Jade S Hiramoto, Peter A Schneider, Michael S Conte, Shant M Vartanian
Journal: Circulation (2020)

Introduction: Peripheral arterial disease is associated with cardiovascular morbidity and mortality, and the burden of PAD can be used to reclassify risk within CVD models. We describe a novel, practical score for quantifying peripheral arterial calcification based on plain x-ray films of the foot (MAC). We hypothesize that high MAC score is associated with risk of death and major adverse cardiovascular events (MACE; defined as MI, coronary intervention, CVA, TIA) in patients with chronic limb-threatening ischemia (CLTI). Methods: This is a single-institution retrospective study of 275 patients who underwent infrainguinal revascularization for CLTI between 1/2011 and 7/2019. MAC scores were calculated by a single blinded reviewer using two-view plain foot radiographs. Each patient was assigned a score of 0-5, with 1 point each for calcifications &gt; 2 cm in the dorsalis pedis, plantar and metatarsal arteries, and &gt; 1 cm in the hallux and non-hallux digital arteries. Results: The distribution of MAC scores was 0 (45%), 1 (4.7%), 2 (8.4%), 3 (18%), 4 (12%) and 5 (11%). MAC scores were trichotomized [mild (0-2), moderate (3-4), severe (5)] and higher scores were associated with male sex, DM, ESRD, and history of smoking. Median follow-up was 620 days (IQR 263-1494). Higher MAC score was significantly associated with MACE (p=0.01) and all-cause mortality (p=0.03), and was predictive of worse MACE-free survival (MACEFS; p=0.01; Figure 1 ). In a Cox Proportional Hazards model for MACEFS that included age; ESRD; CAD; history of CVA or TIA; Society for Vascular Surgery Wound, Ischemia and foot Infection (WIfI) stage; and MAC; the most severe MAC score (HR 1.8 [1.01-3.4] for MAC 5, p=0.04) was significantly associated with worse MACEFS. Conclusions: The MAC score is an independent predictor of MACE-free survival in patients with CLTI. It is a simple, quick and inexpensive tool that has the potential to stratify patients at highest risk of long-term cardiovascular complications.
Abstract 15168: Circulating Cell-free DNA Correlates With Markers of Disease Severity in the Rat Sugen/hypoxia Model of Pulmonary Arterial Hypertension
Authors: Yvette Zou, Samuel B Brusca, Moon K Jang, Hyesik Kong, Jasmine Nelson, Stasia Anderson, Li-Yuan Chen, Audrey Noguchi, Zu-Xi Yu, Junfeng Sun, Sean Agbor-Enoh, Michael A Solomon, Jason M Elinoff
Journal: Circulation (2020)

Introduction: Cell-free DNA (cfDNA) is released into circulation following tissue injury and cell turnover. In cancer and allograft rejection, cfDNA serves as a valuable biomarker for monitoring disease severity, progression, and response to therapy. The goal of the current study is to determine the temporal relationship between plasma cfDNA and disease severity in a PAH rodent model. Methods: Blood collection was performed weekly (weeks 4-11) in both sugen/hypoxia PAH rats (n=12) and age-matched, normoxia controls (n=12). cfDNA was isolated from plasma and concentration was determined by qRT-PCR. Cardiac MRI, cardiac catheterization and necropsy were performed at the end of study. Log-transformed concentrations of cfDNA were compared using linear mixed models. Pearson correlation coefficients were calculated to identify associations between rates of change in cfDNA and measures of disease severity. Results: Plasma cfDNA concentrations were significantly higher in PAH rats beginning at week 5 and continuing through week 10 (P &lt; 0.05 for the comparison at each week; Figure 1). From weeks 4 to 11, there was an overall trend toward increasing cfDNA concentration over time in PAH rats (P = 0.07), whereas concentrations in control rats remained unchanged (P = 0.52). In PAH rats, the rate of change in log-transformed cfDNA concentration correlated inversely with RVEF (r = -0.80, P = 0.003), stroke volume index (r = -0.67, P = 0.02), and positively with total pulmonary resistance index (r = 0.62, P = 0.04). There were non-significant trends between the rate of change in cfDNA concentration and LV end-diastolic volume index (r = -0.54, P = 0.09), and Fulton index (r = 0.55, P = 0.08). Conclusions: Plasma cfDNA is elevated in the rat sugen/hypoxia PAH model and significantly correlated with markers of disease severity. Circulating cfDNA may reflect ongoing pulmonary vascular injury and remodeling, RV strain or both and thus may serve as a novel biomarker of PAH disease progression.
Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma
Authors: Abhishek Tripathi, Edwin Lin, Wanling Xie, Abdallah Flaifel, John A Steinharter, Emily N Stern Gatof, Gabrielle Bouchard, Justin H Fleischer, Nieves Martinez-Chanza, Connor Gray, Charlene Mantia, Linda Thompson, Xiao X Wei, Marios Giannakis, Bradley A McGregor, Toni K Choueiri, Neeraj Agarwal, David F McDermott, Sabina Signoretti, Lauren C Harshman
Journal: Journal for ImmunoTherapy of Cancer (2020)

CD73-adenosine signaling in the tumor microenvironment is immunosuppressive and may be associated with aggressive renal cell carcinoma (RCC). We investigated the prognostic significance of CD73 protein expression in RCC leveraging nephrectomy samples. We also performed a complementary analysis using The Cancer Genome Atlas (TCGA) dataset to evaluate the correlation of CD73 (ecto-5'-nucleotidase (NT5E), CD39 (ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)) and A2 adenosine receptor (A2AR; ADORA2A) transcript levels with markers of angiogenesis and antitumor immune response.Patients with RCC with available archived nephrectomy samples were eligible for inclusion. Tumor CD73 protein expression was assessed by immunohistochemistry and quantified using a combined score (CS: % positive cells×intensity). Samples were categorized as CD73negative (CS=0), CD73low or CD73high (< and ≥median CS, respectively). Multivariable Cox regression analysis compared disease-free survival (DFS) and overall survival (OS) between CD73 expression groups. In the TCGA dataset, samples were categorized as low, intermediate and high NT5E, ENTPD1 and ADORA2A gene expression groups. Gene expression signatures for infiltrating immune cells, angiogenesis, myeloid inflammation, and effector T-cell response were compared between NT5E, ENTPD1 and ADORA2A expression groups.Among the 138 patients eligible for inclusion, 'any' CD73 expression was observed in 30% of primary tumor samples. High CD73 expression was more frequent in patients with M1 RCC (29% vs 12% M0), grade 4 tumors (27% vs 13% grade 3 vs 15% grades 1 and 2), advanced T-stage (≥T3: 22% vs T2: 19% vs T1: 12%) and tumors with sarcomatoid histology (50% vs 12%). In the M0 cohort (n=107), patients with CD73high tumor expression had significantly worse 5-year DFS (42%) and 10-year OS (22%) compared with those in the CD73negative group (DFS: 75%, adjusted HR: 2.7, 95% CI 1.3 to 5.9, p=0.01; OS: 64%, adjusted HR: 2.6, 95% CI 1.2 to 5.8, p=0.02) independent of tumor stage and grade. In the TCGA analysis, high NT5E expression was associated with significantly worse 5-year OS (p=0.008). NT5E and ENTPD1 expression correlated with higher regulatory T cell (Treg) signature, while ADORA2A expression was associated with increased Treg and angiogenesis signatures.High CD73 expression portends significantly worse survival outcomes independent of stage and grade. Our findings provide compelling support for targeting the immunosuppressive and proangiogenic CD73-adenosine pathway in RCC.
Plasma neurofilament light predicts mortality in patients with stroke
Authors: Tania F. Gendron, Mohammed K. Badi, Michael G. Heckman, Karen R. Jansen-West, George K. Vilanilam, Patrick W. Johnson, Alexander R. Burch, Ronald L. Walton, Owen A. Ross, Thomas G. Brott, Timothy M. Miller, James D. Berry, Katharine A. Nicholson, Zbigniew K. Wszolek, Björn E. Oskarsson, Kevin N. Sheth, Lauren H. Sansing, Guido J. Falcone, Brett L. Cucchiara, James F. Meschia, Leonard Petrucelli
Journal: Science Translational Medicine (2020)

Plasma neurofilament light is a reliable, uniform marker to estimate neuroaxonal injury and forecast all-cause mortality across major stroke types.
Do Omega-3 Fatty Acids Benefit Health?
Authors: Gregory Curfman
Journal: JAMA (2020)

Stephen J. Nicholls, MBBS, PhD; A. Michael Lincoff, MD; Michelle Garcia, RN, BSN, CCRC; Dianna Bash, BSN; Christie M. Ballantyne, MD; Philip J. Barter, MBBS, PhD; Michael H. Davidson, MD; John J. P. Kastelein, MD, PhD; Wolfgang Koenig, MD; Darren K. McGuire, MD, MHSc; Dariush Mozaffarian, MD, DrPH; Paul M Ridker, MD; Kausik K. Ray, MBChB, MD, MPhil; Brian G. Katona, PharmD; Anders Himmelmann, MD, PhD; Larrye E. Loss, PharmD, MBA; Martin Rensfeldt; Torbjörn Lundström, MD, PhD; Rahul Agrawal, MD; Venu Menon, MD; Kathy Wolski, MPH; Steven E. Nissen, MD
Abstract 14299: Deep Convolutional Neural Network Analysis of Echocardiographic Images Improves Prediction of Genotype Positivity in Patients With Hypertrophic Cardiomyopathy
Authors: Sae Morita, Kenya Kusunose, Akihiro Haga, Kohei Hasegawa, Muredach P Reilly, Michael A Fifer, Mathew S Maurer, Yuichi J Shimada
Journal: Circulation (2020)

Introduction: Genotyping may provide valuable insights into family screening strategies and prognosis in patients with hypertrophic cardiomyopathy (HCM). On the other hand, genotyping is expensive. Thus, it is important to identify patients who are more likely to be genotype positive. However, conventional prediction models (e.g., the Mayo score) based on clinical and echocardiographic parameters offer only modest accuracy and are subject to inter-observer variability. Hypothesis: Deep convolutional neural network (DCNN) analysis of echocardiographic images improves the ability to predict genotype positivity in HCM compared to the conventional model. Methods: We included 99 patients with HCM who underwent genetic testing for diagnostic and/or family screening purposes. The age at diagnosis was 46±20 years and 65% were male. In each case, we obtained parasternal short- and long-axis as well as all apical images at end-systole. The DCNN underwent 100 steps to develop the model to predict genotype positivity. In each step, we used 80% of the cohort as the training set and the remaining 20% as the test set (i.e., 5-fold cross-validation). We used the Mayo score as the reference model. We compared the area under the receiver operating characteristics curve (AUC) between a combined model using the reference model plus the DCCN-derived probability and the reference model. We calculated the p value by performing 1,000 bootstrapping. Results: Overall, 45 patients (45%) were genotype positive. The model combining the reference and the DCNN-derived models significantly outperformed the reference model (AUC 0.79 [95% CI 0.69-0.87] with the combined model vs. 0.72 [0.61-0.82] with the reference model; p=0.006; Figure). Conclusion: Compared to a conventional model based on clinical and echocardiographic parameters, our new model combining the conventional and DCNN-derived models demonstrated superior ability to predict positive genotype in patients with HCM.
Abstract 204: Association Between Presence of Advanced Airway and Hyperventilation During Pediatric Cardiopulmonary Resuscitation: A Report from the VIPER Collaborative
Authors: Karen OConnell, Sage Myers, Benjamin Kerrey, Alexis Sandler, Ryan Keane, Benjamin Parrish, Ichiro Watanabe, Aaron Donoghue
Journal: Circulation (2020)

Background: Hyperventilation is common during pediatric CPR and has known deleterious hemodynamic consequences. It is not known whether the presence of an advanced airway (AA) is independently associated with hyperventilation. Objective: To determine the independent association between the presence of an AA and hyperventilation during pediatric CPR in a collaborative of pediatric emergency departments using video review during resuscitations. Methods/Design: We present a report from the Videography in Pediatric Emergency Resuscitation (VIPER) Collaborative, a prospective review database. All events where CPR was performed and manual ventilations could be counted for at least 30 seconds were eligible for inclusion. Ventilation rates were counted and expressed in segments corresponding to individual CPR providers (‘compressor segments') and extrapolated to breaths per minute (bpm) where applicable. Hyperventilation was defined as a rate greater than 12 bpm, in accordance with American Heart Association recommendations. Ventilation rates were compared between CPR segments with a natural airway (bag-valve mask device; NA) versus an advanced airway (endotracheal tube or supraglottic airway; AA). Univariate analysis was done by two sided t-testing. Repeated measures logistic regression with random effects modeling (patient as intercept) was performed to determine the independent association of the presence of an AA with hyperventilation. Results/Discussion: 595 compressor segments in 67 CPR events were analyzed. Twenty-six patients underwent intubation and had segments with both NA and AA analyzed. Across all patients, 402/595 (68%) of segments occurred with an AA. Ventilation rates were significantly higher in patients with an AA compared with NA (14 + 10 bpm vs. 24 + 17 bpm, p &lt; 0.001). By multivariate analysis, the presence of an advanced airway was independently associated with hyperventilation (AOR 12.2, 95% CI 5.0 - 30.3) during pediatric CPR. Future studies should examine methods of limiting manual hyperventilation during pediatric CPR, as well as the impact of ventilation rates on patient outcomes.
Abstract 15826: SCUBE1 Controls BMPR2-relevant Pulmonary Endothelial Function: Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension
Authors: Wei Sun, Ying Tang, Yi-Yin Tai, Adam Handen, Jingsi Zhao, Gil Speyer, Yassmin Al Aaraj, Annie Watson, Makenna Romanelli, John C Sembrat, Mauricio Rojas, Marc A Simon, Yingze Zhang, Janet S Lee, Zeyu Xiong, Partha Dutta, Sathish Vasamsetti, Dennis M McNamara, Bryan McVerry, Charles F MCTIERNAN, Frank Sciurba, Seungchan Kim, Akaya Smith, Jeremy A Mazurek, Yuchi Han, Anjali Vaidya, Mehdi Nouraie, Neil Kelly, Stephen Y Chan
Journal: Circulation (2020)

Introduction: Pulmonary arterial hypertension (PAH) is a morbid vascular disease where mutations of bone morphogenetic protein receptor 2 (BMPR2) control pulmonary endothelial pathophenotypes. Transcriptomic screening from endothelial cells (ECs) derived from hereditary BMPR2-driven disease offers an opportunity to identify novel effectors in PAH pathogenesis. Methods: Public RNA-sequencing data were analyzed from inducible pluripotent stem (iPS) cell-derived endothelial cells with and without BMPR2 mutations. Candidate genes were assessed in cultured pulmonary arterial ECs (PAECs) and in rodent and human PAH. Correlations were assessed of human plasma expression with clinical disease indices. Results: Signal Peptide CUB-EGF-Domain Containing Protein 1 (SCUBE1), a putative binding partner to BMPR2, was differentially expressed in ECs carrying BMPR2 mutations. SCUBE1 was enriched in PAECs, dependent on hypoxia inducible factor-1α, and downregulated by PAH triggers, including BMPR2 knockdown, hypoxia, and IL-1β exposure. In vitro analyses defined SCUBE1 as a pathogenic effector activating BMPR2-associated SMAD1/5/9, thus regulating endothelial angiogenic potential, proliferation, and apoptosis. SCUBE1 was decreased specifically in plasma and lungs in rodents and patients with PAH but not in those with pulmonary hypertension due to left heart disease, or in the patients of other acute and chronic cardiopulmonary pathologies, including pneumonia, acute lung injury, chronic obstructive pulmonary disease, ischemic heart disease, and cardiomyopathy. An optimal plasma SCUBE1 cut point of 5.02 ng/mL was defined to diagnose PAH from control cohort with a sensitivity of 0.65 and a specificity of 0.82. In PAH patients, plasma SCUBE1 levels negatively correlated with pulmonary arterial pressure, pulmonary vascular resistance, and right ventricular dysfunction. Conclusions: Guided by iPSC-EC sequencing, SCUBE1 was identified as a downregulated secreted factor in PAH, controlling endothelial pathophenotypes and correlated with disease indices. Clinically, SCUBE1 is a sensitive and specific PAH diagnostic marker. It may also serve as a therapeutic target given its inherent links to controlling PAH predisposition and severity.