tbuckley/cabot-search huggingface dataset:
Abstract 15696: Outcomes With Intra-Aortic Balloon Pump versus Percutaneous Ventricular Assist Device for Left Ventricular Venting in Adults Receiving Venoarterial Extracorporeal Life Support: An ELSO Registry Analysis
Authors: Brooks Willar, Jose Nunez, Kennedy Kevin, Peter Rycus, Joseph Tonna, Navin K Kapur, Shahzad Shaefi, Marwa Sabe, Arthur R Garan, Edward W Grandin
Journal: Circulation (2020)

Background: Insufficient left ventricular (LV) unloading during venoarterial extracorporeal life support (VA-ECLS) can result in poor LV recovery and inability to wean from support. Published data suggest a survival benefit with LV mechanical venting (MV), but there is limited data comparing modalities. Methods: We queried the ELSO registry from 2010-2019 for adults undergoing VA-ECLS with MV and stratified them by intra-aortic balloon pump (IABP) or percutaneous ventricular assist device (pVAD). We excluded patients with pulmonary embolism, heart transplant, congenital and valvular heart disease, aortic disease, and central cannulation. We performed a subgroup analysis excluding extracorporeal cardiopulmonary resuscitation (ECPR). The primary outcome was in-hospital mortality. Secondary outcomes were on-support mortality, medical and cannula site bleeding, hemolysis, ischemic stroke, limb ischemia, and renal injury. We used multivariable logistic regression modeling to adjust for clinical covariates. Results: Among 3353 adults with MV on VA-ECLS, 2782 (83%) were vented with IABP and 571 (17%) with pVAD. IABP patients were less likely to be supported for ventricular arrhythmia (9.6% vs 14.3%) and had lower rates of pre-ECLS arrest (49% vs 66%) and concomitant renal (13.5% vs 34.5%), liver (3.4% vs 9.3%), and respiratory (17.6% vs 37.0%) failure, p&lt;0.001 for all. On-support (40.8% vs 45.5%, p=0.037) and in-hospital (55.9% vs 60.6%, p=0.038) mortality were lower with IABP vs pVAD. In multivariate modeling, IABP was associated with a significantly lower odds of medical bleeding with a trend towards lower in-hospital mortality that was significant after excluding ECPR patients (Figure). Conclusion: In adults with MV on VA-ECLS, IABP compared to pVAD is associated with a significantly lower risk of bleeding and a strong signal of improved survival. We cannot exclude residual unmeasured confounding, so prospective studies are needed to compare MV devices.
Abstract IA-14: Understanding inherited risk for pancreatic cancer
Authors: Alison P. Klein
Journal: Cancer Research (2020)

Abstract Pancreatic cancer is the 3rd leading cause of cancer death in the Unites States and the global burden of pancreatic cancer has more than doubled over the past 25 years. Inherited genetic factors explain 22-36% of pancreatic cancer. This includes both high-risk pathogenic variants in hereditary cancer genes and genes associated with hereditary pancreatitis as well as common variants identified in genome-wide association studies. Environmental factors, including cigarette smoking may influence the impact of these genetic variants. High risk pathogenic variants are present in 5-10% of all pancreatic cancer patients and up to 20% of patients with a family history of pancreatic cancer. Studies to identify the genetic basis of the remaining 80% of families with a clustering of pancreatic cancer are ongoing. Identification of the genetic changes that underlie pancreatic cancer not only provide insight into the etiology of this fatal cancer but also provides an opportunity to guide early detection strategies. Citation Format: Alison P. Klein. Understanding inherited risk for pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-14.
The SCARE 2020 Guideline: Updating Consensus Surgical CAse REport (SCARE) Guidelines
Authors: Riaz A. Agha, Thomas Franchi, Catrin Sohrabi, Ginimol Mathew, Ahmed Kerwan, Achilles Thoma, Andrew J. Beamish, Ashraf Noureldin, Ashwini Rao, Baskaran Vasudevan, Ben Challacombe, Benjamin Perakath, Boris Kirshtein, Burcin Ekser, C.S. Pramesh, Daniel M. Laskin, David Machado-Aranda, Diana Miguel, Duilio Pagano, Frederick H. Millham, Gaurav Roy, Huseyin Kadioglu, Iain J. Nixon, Indraneil Mukherjee, James A. McCaul, James Chi-Yong Ngu, Joerg Albrecht, Juan Gomez Rivas, Kandiah Raveendran, Laura Derbyshire, M. Hammad Ather, Mangesh A. Thorat, Michele Valmasoni, Mohammad Bashashati, Mushtaq Chalkoo, Nan Zun Teo, Nicholas Raison, Oliver J. Muensterer, Patrick James Bradley, Prabudh Goel, Prathamesh S. Pai, Raafat Yahia Afifi, Richard David Rosin, Roberto Coppola, Roberto Klappenbach, Rolf Wynn, Rudy Leon De Wilde, Salim Surani, Salvatore Giordano, Samuele Massarut, Shahzad G. Raja, Somprakas Basu, Syed Ather Enam, Todd Galvin Manning, Trent Cross, Veena KL. Karanth, Veeru Kasivisvanathan, Zubing Mei
Journal: International Journal of Surgery (2020)
Abstract 14517: Abnormal Flow Conditions Promote Endocardial Fibroelastosis via the Induction of Endothelial-to-mesenchymal Transition, Which is Responsive to Losartan Treatment
Authors: Nicholas Oh, XueChong Hong, Ilias P Doulamis, Elamaran Meibalan, Teresa Peiseler, Juan M Melero-Martin, Guillermo Garcia-Cardena, Ingeborg Friehs, Pedro J Del Nido
Journal: Circulation (2020)

Introduction: Endocardial Fibroelastosis (EFE) is a condition defined by the formation of fibrotic tissue on the endocardium, stunting cardiac development. The presence of EFE restricts diastolic compliance, leading to systolic and diastolic heart failure, and contributing to higher morbidity and mortality, particularly in Hypoplastic Left Heart Syndrome. While research suggests that EFE forms through aberrant endothelial-to-mesenchymal transition (EndoMT), the trigger of its formation is still speculative. Anecdotally, however, we have observed EFE development in patients with abnormal left ventricular flow. Objective: Our objective is to study whether the absence of normal flow induces EndoMT in neonatal endocardium and promotes EFE development, and whether losartan treatment, which can decrease TGFβ production to impair EndoMT, can abrogate EFE formation. Methods and Results: Using a rodent model of EFE, we establish three flow conditions in neonatal hearts: Normal Flow (NF), Static/no flow (S), and Regurgitant Flow (RF). Histologic analysis demonstrates EFE development in S and RF conditions, but not in NF conditions. Using qPCR, Western Blot Assay, and immunohistochemistry, we demonstrate that S and RF significantly increase mRNA and protein expression of EndoMT markers (αSMA, SNAIL), and EndoMT-related signaling pathways (TGFβ, NOTCH1) whereas NF conditions do not. With losartan treatment, we observe a significant decrease in EFE in neonatal hearts documented by histology and decreased mRNA and protein expression of EndoMT markers. To determine whether our findings are translatable to humans, human endocardial endothelial cells were isolated from left ventricular tissue and subjected to two flow conditions: static and laminar shear stress (LSS). By RNAseq analysis, we demonstrate that laminar shear stress suppresses the expression of genes critical for mesenchymal differentiation and Notch signaling, which are both associated with EndoMT progression. Conclusions: Our data demonstrates that the absence of normal flow provides an environment that promotes EFE development through activated EndoMT. Further, we identify losartan as a potential therapy for EFE, as it is able to abrogate EFE development in our animal model.
LIVER METASTASES FROM COLORECTAL CANCER WERE MORE SUSCEPTIBLE TO COVID-19
Authors: X. Zhong, W. Zhang, J. Chen, S. Tang
Journal: Hepatology (2020)

Background: Coronavirus diseases 2019 (COVID-19) are severe and prevalent diseases all over the world, which have caused more than 10 million infections and more than half million deaths so far Angiotensin I-converting enzyme 2(ACE2) and transmembrane serine protease 2 (TMPRSS2) are the entry receptors that play crucial roles in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19 Due to the high expression of ACE2/ TMPRSS2, and the immunosuppression caused by cancer and anti-cancer therapy, cancer patients are more likely to be infected with SARS-CoV-2 Previous studies have showed that the high expression of ACE2/TMPRSS2 in lung cancer, tongue cancer and colorectal cancer may be related to the high susceptibility of SARS-CoV-2 However, the susceptibility of liver metastases has not been elucidated Methods: We explored the Gene Expression Omnibus(GEO) database to mine the datasets of liver metastases from colorectal cancer with matched normal liver R package limma was used to analysis the datasets Paired t-test was used to compare the expression of ACE2 and TMPRSS2 between groups Results: GSE38174 dataset of 90 cases was enrolled to compare the expression levels of ACE2 and TMPRSS2 in liver metastases, matched liver Halo of metastases and normal liver The results showed that ACE2 expression in liver metastases was higher than that in liver Halo of metastases and normal liver (3 303±0 426, 2 328±0 228 and 2 522±0 173;metastases vs Halo, p=0 016;metastases vs normal, p=0 065;and Halo vs normal, p=0 272;Figure A) The expression of TMPRSS2 in liver metastases was significant higher than that in liver Halo or normal liver (3 006±0 258, 2 511±0 118 and 2 409±0 129;metastases vs Halo, p=0 075;metastases vs normal, p=0 027;and Halo vs normal, p=0 250;Figure B) Conclusion: Liver metastases have a high-expression of ACE2 and TMPRSS2, which may make patients more susceptible to SARS-CoV-2 infection In addition, liver metastases could serve as a target of SARS-CoV-2, casing liver damage and virus replication and transport However, as the first study on the genetic susceptibility of liver metastases to SARS-CoV-2 from public databases, our research needs to be further verified with real-world data  Abbreviations: ACE 2: angiotensin I-converting enzyme 2;COVID-19: coronavirus diseases 2019;GEO: Gene Expression Omnibus;SARSCoV- 2: severe acute respiratory syndrome coronavirus 2;TMPRSS2: transmembrane serine protease 2
Detection of Unexpected Brown Tumors Due to Hyperparathyroidism Diagnosed by 18F-FDG PET/CT
Authors: Astrid Geysen, Koen Van Laere, Raf Verscuren
Journal: Clinical Nuclear Medicine (2020)

Abstract A 27-year-old man was called to receive a kidney transplant. The preoperative CT of the chest showed multiple osteolytic lesions, as well as a hypodense structure posterior in the right thyroid lobe. Blood analysis showed elevated parathyroid hormone, phosphorus, and alkaline phosphatase levels, with normal calcium and 25-OH-vitamin D. 18 F-FDG PET/CT demonstrated generalized elevated FDG uptake in the bone (due to hyperparathyroidism), as well as multiple hypermetabolic focal lesions spread throughout the bone (fitting brown tumors). The nodule posterior of the right thyroid lobe showed an intense FDG uptake as well, suggestive of a parathyroid adenoma/hyperplasia. Histopathology confirmed the diagnosis.
Abstract 16392: The Effect of Dapagliflozin on Anemia in Patients With Heart Failure and Reduced Ejection Fraction: An Analysis of DAPA-HF
Authors: Kieran Docherty, Silvio E Inzucchi, Lars Kober, Mikhail Kosiborod, Anna Maria Langkilde, Feilpe Martinez, Olof Bengtsson, Piotr Ponikowski, Marc S Sabatine, Mikaela SjÃ¶strand, Scott Solomon, Pardeep S Jhund, John J McMurray
Journal: Circulation (2020)

Background: Anemia is common and associated with worse outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We examined: 1) whether dapagliflozin corrected anemia in these patients, and 2) the effect of dapagliflozin on outcomes, in patients with or without anemia, in DAPA-HF. Methods: Anemia was defined as baseline hematocrit &lt;39% in men and &lt;36% in women (WHO). Correction of anemia was defined as two consecutive hematocrit measurements above these thresholds at any time during follow-up (follow-up visits: 2 weeks, 2 and 4 months and 4-monthly thereafter). The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Findings: Of the 4744 patients randomized in DAPA-HF, 4691 had a baseline hematocrit and 1032 were anemic (22.0%). Anemia was corrected in 62% of patients in the dapagliflozin group, compared with 41% of patients in the placebo group (odds ratio 2.37 [95% CI 1.84-3.04]; p&lt;0.001). The effect of dapagliflozin on the primary outcome was consistent in anemic and non-anemic patients (HR 0.68 [95% CI 0.52-0.88] versus 0.76 [0.65-0.89]; P-interaction=0.44) [Figure]. A consistent benefit was also observed for the secondary outcomes, irrespective of anemia status t baseline. Patients with resolution of anemia had better outcomes than those with persisting anemia: rate of primary outcome 9.9 per 100 patient-years (95% CI 8.0-12.4) in those with resolution versus 24.1 per 100 patient-years (20.4-28.3) in those without anemia resolution. Interpretation: Anemia was common in patients in DAPA-HF and associated with worse outcomes. Resolution of anemia was associated with better outcomes than persistence of anemia, regardless of treatment allocation. Although dapagliflozin corrected anemia more often than placebo, treatment with dapagliflozin improved outcomes, irrespective of anemia status.
A rash in a hairy situation: Leukocytoclastic vasculitis at presentation of hairy cell Leukemia
Authors: Justin T. Moyers, Lawrence W. Liu, Stephanie Ossowski, Lindsey Goddard, Muhammad O. Kamal, Huynh Cao
Journal: American Journal of Hematology (2019)

A 62-year-old woman presented with a three-month history of fatigue, fevers, bruising, epistaxis, and rash. Physical examination revealed erythematous and violaceous non-blanching papules and macules, coalescing into patches and plaques on the bilateral lower and upper extremities, abdomen, and back (See Image 1 Panel A and B). Physical examination revealed bilateral supraclavicular lymphadenopathy and hepatosplenomegaly. Laboratory studies revealed pancytopenia. Bone marrow biopsy revealed hypercellular marrow with "fried egg" appearance, and immunophenotyping positive for CD11c, CD25, and CD103, diagnostic for hairy cell leukemia. A skin lesion biopsy revealed leukocytoclasis with extravasated erythrocytes on H&E (See Image 1 Panel C), as well as direct immunofluorescence positive staining for perivascular IgA, IgG, IgM, C3, and fibrinogen (See Image 1 Panel D), consistent with leukocytoclastic vasculitis. She was treated with topical triamcinolone and seven -day induction therapy with cladribine. Complete resolution of rash and leukemia occurred rapidly with sustained remission 14 months later. Malignancy is frequently diagnosed concurrent to autoimmune diseases including vasculitis.1 Vasculitis occurs simultaneously in 5% to 8% of primary lymphoproliferative disorders.2 This occurrence has been previously hypothesized to be autoimmune in nature due to cross-reactivity between hairy cells and vascular endothelium.3 Case reports have similarly shown resolution of symptoms after treatment of primary underlying hematologic malignancy.4, 5 Therefore, hematologic malignancies should be considered as a potential underlying etiology for newly diagnosed leukocytoclastic vasculitis. The authors declare no potential conflicts of interest.
DNA methylation signature in blood mirrors successful weight-loss during lifestyle interventions: the CENTRAL trial
Authors: Maria Keller, Anat Yaskolka Meir, Stephan H. Bernhart, Yftach Gepner, Ilan Shelef, Dan Schwarzfuchs, Gal Tsaban, Hila Zelicha, Lydia Hopp, Luise Müller, Kerstin Rohde, Yvonne Böttcher, Peter F. Stadler, Michael Stumvoll, Matthias Blüher, Peter Kovacs, Iris Shai
Journal: Genome Medicine (2020)

Abstract Background One of the major challenges in obesity treatment is to explain the high variability in the individual’s response to specific dietary and physical activity interventions. With this study, we tested the hypothesis that specific DNA methylation changes reflect individual responsiveness to lifestyle intervention and may serve as epigenetic predictors for a successful weight-loss. Methods We conducted an explorative genome-wide DNA methylation analysis in blood samples from 120 subjects (90% men, mean ± SD age = 49 ± 9 years, body mass-index (BMI) = 30.2 ± 3.3 kg/m 2 ) from the 18-month CENTRAL randomized controlled trial who underwent either Mediterranean/low-carbohydrate or low-fat diet with or without physical activity. Results Analyses comparing male subjects with the most prominent body weight-loss (responders, mean weight change − 16%) vs. non-responders (+ 2.4%) ( N = 10 each) revealed significant variation in DNA methylation of several genes including LRRC27 , CRISP2 , and SLFN12 (all adj. P &lt; 1 × 10 −5 ) . Gene ontology analysis indicated that biological processes such as cell adhesion and molecular functions such as calcium ion binding could have an important role in determining the success of interventional therapies in obesity. Epigenome-wide association for relative weight-loss (%) identified 15 CpGs being negatively correlated with weight change after intervention (all combined P &lt; 1 × 10 − 4 ) including new and also known obesity candidates such as NUDT3 and NCOR2 . A baseline DNA methylation score better predicted successful weight-loss [area under the curve (AUC) receiver operating characteristic (ROC) = 0.95–1.0] than predictors such as age and BMI (AUC ROC = 0.56). Conclusions Body weight-loss following 18-month lifestyle intervention is associated with specific methylation signatures. Moreover, methylation differences in the identified genes could serve as prognostic biomarkers to predict a successful weight-loss therapy and thus contribute to advances in patient-tailored obesity treatment.
Abstract 14077: One-year Outcome After PCI in Patients Treated Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers - Subanalysis From Multicenter Registry -
Authors: Inagaki YUSUKE, Kentaro Jujo, Hiroyuki Tanaka, Toshiaki Oka, KAZUHO KAMISHIMA, Hiroshi Koganei, Hiroshi Kobayashi, Fumiaki Mori, Tomohiro Sakamoto, Yoshimi Ota, Junichi Yamaguchi, Nobuhisa Hagiwara
Journal: Circulation (2020)

Background: The prescription of inhibitors for renin-angiotensin-aldosterone system (RAAS) is associated with improved prognosis but have respectively different mechanisms of action in patients with coronary artery disease (CAD). We aimed to compare the clinical outcomes between angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) therapy in patients with CAD undergoing percutaneous coronary intervention (PCI). Methods: This study is a subanalysis from the TWINCRE registry that is a multicentral prospective cohort including patients who underwent PCI. After excluding 18 patients who received both ACEi and ARB from 2,896 registered patients, we ultimately evaluated 369 patients treated with ACEi, 492 with ARB and 541 without ACEi or ARB. The primary endpoint was a major adverse cardiovascular and cerebrovascular events (MACCE) including death from any cause, acute coronary syndrome, stent thrombosis, stroke and hospitalization for heart failure. The impact of RAAS inhibitors on all-cause mortality alone was also evaluated. Results: During the observation period with 366 days of a median follow-up, Kaplan-Meier analysis revealed that the ARB group had the lowest rate of MACCE than other two groups (Log-rank for trend, p&amp;lt; for &lt; 0.0001, Figure). Regarding all-cause mortality, the ARB group and ACEi group had comparable rates for MACCE, which were lower than the no-ACEi/ARB group (p&amp;lt; for &lt; 0.0001). In a Cox regression analysis, after adjusting with age, gender, comorbidities, multivessel disease, acute myocardial infarction, and medications at discharge including dual antiplatelet therapy and statins, ARB therapy was still had a superiority to ACEi therapy regarding with MACCE (hazard ratio: 0.54, 95% confidence interval: 0.30-0.98). Conclusion: In the multicenter cohort study, ARB therapy was associated with better one-year clinical outcomes compared to ACEi therapy in patients undergoing PCI.
Abstract 13174: Coronary Origin Patterns: Utility in Echocardiographic Diagnosis of Forme Fruste Right-left Bicuspid Aortic Valve
Authors: Daniel N Beauchamp, Claudio Ramaciotti, Paul Brown, Poonam Thankavel
Journal: Circulation (2020)

Introduction: Bicuspid aortic valve (BAV) is a common congenital heart defect associated with coronary artery (CA) variants, including higher incidence of left CA dominance and shorter left main CA length. In patients with right-left fusion (R/L) BAV, we observed that the origins of left and right coronaries are in closer proximity than in normal patients. ‘Forme fruste’ types of R/L BAV are subtle and difficult to diagnose, hence this coronary pattern can aid in diagnosis. We defined intercoronary distance as the angle separating the left and right coronary ostia relative to the aortic valve center. Hypothesis: The coronary angle is more acute in R/L BAV than in normal aortic valves. Methods: A retrospective review of pediatric echocardiograms with R/L BAV at a single institution (12/2010-11/2018) was performed; coronary angles were measured and compared to age-matched controls. Those with inadequate images or anomalous coronary origins were excluded. Results: We identified 193 patients with R/L BAV (64% male) and 136 patients with normal aortic valves (57% male). Coronary angle was significantly more acute in R/L BAV than in controls (117.7°±16.8° vs 139.0°±10.1°, p&lt;0.0001). This was independent of age, gender, or other cardiac defects. This relationship remained when BAV patients with abnormal aortic Z-scores were removed from analysis (119.2°±15.3° vs 139.0°±10.1°, p&lt;0.0001), ruling out an effect of abnormal aortic annulus or root. Conclusions: Coronary origins are in closer proximity in R/L BAV independent of annulus/root geometry, associated cardiac defects, age, or gender. This new finding may assist in echocardiographic diagnosis of subtle subtypes of BAV.
Deferring a Change in the Standard of Care for Small Cell Lung Cancer Brain Metastases
Authors: Charles B. Simone
Journal: JAMA Oncology (2020)

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Nanoparticle delivery improves the pharmacokinetic properties of cyclic dinucleotide STING agonists to open a therapeutic window for intravenous administration
Authors: Mohamed Wehbe, Lihong Wang-Bishop, Kyle W. Becker, Daniel Shae, Jessalyn J. Baljon, Xinyi He, Plamen Christov, Kelli L. Boyd, Justin M. Balko, John T. Wilson
Journal: Journal of Controlled Release (2020)