tbuckley/cabot-search huggingface dataset:
Abstract 10680: Unsupervised Machine Learning Clustering Identifies Phenotypes of Optimal Candidates in Mitraclip Patients
Authors: Chiehju Chao, Han-Lun Wu, Amith Seri, Anusha Shanbhag, Corbin Rayfield, Yuxiang Wang, Sean Smith, Floyd D Fortuin, John Sweeney, Mackram F Eleid, Mohamad Alkhouli, Charanjit RIHAL, David R Holmes, Peter Pollak, Abdallah El Sabbagh, Steven Lester, Win K Shen, Bhavik Patel, Reza Arsanjani
Journal: Circulation (2021)

Introduction: Unsupervised machine learning (ML) can provide insight into a dataset without significant expert time for annotation and labeling, but was never used to assess the heterogeneous MitraClip population. Hypothesis: We hypothesized that unsupervised k-means ML could identify prognostically-distinct phenogroups in MitraClip patients without a priori knowledge of the dataset. Methods: Patients who underwent MitraClip (June 2014-September 2020) at Mayo Clinic sites were identified from the Mayo institutional NCDR database for baseline and follow-up data. Variables with ≥ 50% missing data were excluded. A k-means algorithm was used for clustering analysis. Input variables were grouped according to 4 distinct k-means determined clusters. Kaplan-Meier survival analysis was used to assess the survival of each cluster. Results: A total of 389 consecutive patients were included in the final analysis, and 95 unique variables were used. The mean age was 80.3±8.7 years; 256 (65.8%) were male. The mean STS MV Replace score was 9.1±5.7. Fifty-five (14.5%) patients died during the mean follow duration (185 days). Kaplan-Meier analysis showed significant survival differences among clusters (Figure 1). The cluster (cluster 2, n=120) with best survival performance (all-cause mortality 3.3%) had features of non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation. Cluster 3 (n=66) had the worst survival performance (all-cause mortality 27.3%) and opposite features than cluster 2. Conclusions: Unsupervised ML can identify distinct phenotype clusters with prognostic significance in MitraClip patients. Patients with non-calcified mitral leaflets, nonischemic cardiomyopathy, and less than moderate tricuspid regurgitation are intrinsically different from other MitraClip patients and should be considered the potential optimal candidates.
Factors Influencing Change in MCV and Age at Transplantation in the Belgian Sickle Cell Disease Registry
Authors: Sarah Wambacq, Beatrice Gulbis, Fleur Samantha Benghiat, Bénédicte Brichard, Bruwier Annelyse, Laurence Dedeken, Bram De Wilde, Marie-Françoise Dresse, Andre Efira, Catherine Heijmans, Veerle Labarque, Phu-Quoc Le, Philip Maes, Pierre Philippet, An Van Damme, Anna Vanderfaeillie, Alina Ferster
Journal: Blood (2021)
PATH-24. COPY NUMBER ALTERATIONS IN NOTCH PATHWAY GENES ARE PROGNOSTIC IN A SUBSET OF DIFFUSE ASTROCYTIC GLIOMAS
Authors: Nicholas Nuechterlein, Patrick Cimino
Journal: Neuro-Oncology (2021)

Abstract Inactivating mutations in NOTCH1 occur in many cancer types and are frequently observed in IDH-mutant, 1p/19q-codeleted oligodendroglioma. Although the role of NOTCH1 as a tumor suppressor in diffuse glioma has become appreciated in human tissue and small animal models, the spectrum of inactivating mutations in Notch pathway genes in diffuse astrocytic gliomas has not been well described. To address this, we queried the TCGA lower-grade glioma and glioblastoma datasets to establish the extent of inactivation of Notch pathway genes, specifically by cataloging single nucleotide variants and those with copy number loss or deletion. Key alteration frequencies were found to be similar in two-independent glioma cohorts (Col, MSK). Notch pathway genes with inactivating alterations (overwhelmingly copy number loss) were present in 77% of TCGA diffuse gliomas. Across all diffuse gliomas, DLL3 loss was the most common alteration (TCGA 31%). For IDH-mutant diffuse astrocytic gliomas, JAG2 loss was the most common alteration (TCGA 23.0%, Col 35%, MSK 27%). DLL1 loss and MAML1 loss were mutually exclusive (p&amp;lt; 0.001) in TCGA IDH-mutant astrocytomas with a combined frequency of 39% (Col 47%, MSK 56%). The presence of any alteration in the top 10 altered Notch pathway genes indicated a shorter progression-free survival (p = 0.028) for TCGA IDH-mutant diffuse astrocytomas. For IDH-wildtype diffuse astrocytic gliomas, EP300 loss was the most common inactivating alteration (TCGA 35.4%, Col 49%, MSK 38%). EP300 loss, DLL1 loss, DLL4 loss were mutually exclusive (p = 0.006) in TCGA IDH-wildtype diffuse astrocytic gliomas with a combined frequency of 61% (Col 72%, MSK 66%). The presence of alterations in any of these three genes indicated a decreased overall survival (p = 0.045) in TCGA IDH-wildtype diffuse astrocytic gliomas. Overall, loss of differential Notch pathway genes has prognostic implications in both IDH-wildtype and IDH-mutant diffuse astrocytic gliomas.
Abstract 11675: Global Cardio Oncology Registry: Structure for a Multinational Collaboration
Authors: Diego B Sadler, Rohit Moudgil, Teske Arco, Patrick H Collier, Abdullah Sarkar, Ana Barac, Brown Sherry Ann, Joerg Herrmann, Anita M Deswal
Journal: Circulation (2021)

Introduction: Global collaboration in cardio-oncology (CO) is needed to understand the prevalence of cancer treatment related cardiovascular disease (CTRCD) in different risk groups, practice settings and geographic locations. Furthermore, socio-economic and ethnic disparities may impact access to care. Methods: We assembled cardiologists (CA) and oncologists from academic and community settings to collaborate in the first global cardio-oncology registry (G-COR). US and international CO physicians participated in the first global virtual meeting to assess feasibility and structure for G-COR. Subsequently, a survey for sites resources, demographics and intention to participate was conducted. Results: Responses with sites demographics from 104/140 sites invited: 43 US sites from 23 states and 61 international sites from 5 continents indicated decision to participate in G-COR. Sites were more commonly led by CA (74/99) than CA and oncologists (25/99) and were more often University/teaching (68/101) than community based (33/101). Significant minorities/disadvantaged CO patient population were reported by 32/43 US sites versus 16/60 international sites. Average number CO patients treated per month was 83, range (5-1,000). Breast cancer was the first or second G-COR priority for 84 centers, hematological malignancies (HEM) for 66 centers, and immune check point inhibitors (ICI) for 36 centers. Echocardiography with strain imaging is available in 92/95 participating sites and cardiac MRI in 80/86 sites. Biomarkers are used only in suspected or confirmed CTRCD in 56/96 sites and for risk stratification in high risk patients in 40/96 sites. Subsequently, scientific committee and topic committees for breast cancer, HEM, ICI, and disparities in CO were established. A pilot phase utilizing a RedCap Cloud platform will start enrolling patients in the last quarter of 2021 and the registry for all main pillars will launch in early 2022. Conclusions: We present a global initiative for conducting collaborative research. Information learned G-COR will help understanding risk factors impacting CTRCD in different geographic locations and therefore help reducing access gaps in CO care. Additionally, mitigating strategies can be devised for the future.
Abstract 10909: Purulent Pericarditis Can Be Near Fatal
Authors: Senthil S Balasubramanian, Safwan Gaznabi, Philip Krause, Jordan Harris, Arman Qamar, Robert Gordon, Gregory Mishkel
Journal: Circulation (2021)

A previously healthy 27 years-old male presented with 2 weeks of substernal chest pain, progressive dyspnea, palpitations, dizziness, and(&amp;) fever. On exam, he had tachypnea &amp; tachycardia, was hypotensive with an elevated JVP &amp; muffled heart sounds. Labs showed elevated WBC, CRP, lactate &amp; high sensitive troponin. Negative for COVID-19, flu. EKG showed sinus tachycardia. CT showed large pericardial effusion with gas in the pericardial space. Echo (Figure 1) revealed large pericardial effusion with tamponade. Emergent pericardiocentesis was performed draining a liter of straw-colored thick fluid (fluid: serum LDH &gt;3) (Figure 2). Cultures grew Strep. Anginosus &amp; Propionibacterium acnes. Extensive infectious &amp; immunological workup returned negative. He had initially improved on broad-spectrum antibiotics however declined clinically on day 5. Repeat CT (Figures 3 &amp; 4) showed recurrent pericardial effusion &amp; mediastinal abscess with trace extravasation of contrast from the esophagus to posterior mediastinum. We present a case of esophageal perforation leading to Pyopneumopericardium. Stephenson et al. reported a case series of 13 patients with esophagopericardial fistulas &amp; pyopneumopericardium with a 100% mortality rate. Another case series showed survival rates of only 17% in 60 patients with pyopneumopericardium secondary to esophageal perforation. Erosion of esophageal ulcers, ingestion of foreign body, iatrogenic, trauma, malignancy, localized inflammation can lead to esophageal perforation. Streptococcus pneumoniae &amp; Staphylococcus aureus are common pathogens involved. Constrictive pericarditis is a possible complication in up to 20 to 30%. Our patient underwent pericardial window &amp; surgical debridement followed by EGD-guided gastro-jejunal tube placement. He did well after 4 weeks of IV antibiotics. Our case demonstrates that early recognition &amp; intervention can favorably alter the course of this potentially fatal cardiac condition.
Abstract 14467: Machine Learning for Identifying Salient Regions on the Coronary Artery on CT for Radiomic Feature Extraction and Characterization of CAD
Authors: Rohan Dhamdhere, Gourav Modanwal, Anant Madabhushi, Milind Y Desai, Vidya Sankar Viswanathan
Journal: Circulation (2021)

Introduction: Radiomics is a quantitative approach that allows for high throughput extraction of image features such as texture. It has been used for characterization of coronary artery disease (CAD). However, the reliability of radiomic features (RFs) varies with the image segmentation quality. We present a new strategy to establish a segmentation confidence map spatially across the coronary arteries in the dataset. We then evaluate the quality of RFs in salient (high confidence) and non-salient (low confidence) regions in the coronary artery. Purpose: To identify salient regions in the coronary artery, providing high segmentation certainty as well as a site for informative radiomic feature extraction, useful in CAD characterization. Methods: In our approach, we first applied a deep learning-based segmentation model (U-Net with ResNet backbone) to segment the coronary arteries (Fig. 1a). Next, we constructed a mean probability atlas from the segmentation probability maps, using fiducial registration (Fig. 1b). Finally, we identified salient and non-salient regions within the segmentation (Fig. 1c) by masking the mean probability atlas with the predicted segmentation and then thresholding them. Human expert-generated manual segmentation was used as ground truth. RFs—shape (26), first order (19) and second order (75)—were extracted from salient and non-salient regions for comparative correlation analysis with features from ground truth segmentation. A higher correlation implies that these features are equally informative as those from the manual segmentation. Results: The model achieved a dice score of 79.8% on the hold-out set. The RFs extracted only from the salient regions (Proximal portion of RCA and LAD) of the coronary artery display strong correlations with RFs extracted from manual segmentations (Fig 1d). Conclusion: We present a framework to identify regions for optimal extraction of RFs for improved CAD characterization.
Abstract 10166: Incidence and Outcomes of Heparin-Induced Thrombocytopenia Among Patients Undergoing Left Ventricular Assist Device Implantation
Authors: Temitope Ajibawo, Adeniyi Okunade, Priyank Chauhan, Oluwatimilehin Okunowo
Journal: Circulation (2021)

Background and Objectives: Heparin-induced thrombocytopenia (HIT) increases the risk of thromboembolic and bleeding events. HIT is also a well-known complication in patients undergoing left ventricular assist device (LVAD) implantation, although most studies are limited to case reports/series and single-center experiences. The main objective of this study is to examine the incidence and impact of HIT on outcomes in LVAD implants using a nationwide database. Methods: Using the National Inpatient Sample database (2007-2014), we identified patients ≥ 18 years that underwent LVAD implants using ICD-9 codes. LVAD implants were stratified by the presence of HIT. The primary and secondary endpoints were the impact of HIT on mortality and other outcomes respectively. Results: Out of the 15,083 LVAD implantations, HIT occurred in 331 (2.2%). Although not statistically significant, the annual incidence of HIT rose from 1.3% in 2009, peaked at 3.3% in 2012 and decreased to 2.0% (ptrend = 0.6171). In-hospital mortality (OR 2.21, 95% CI 1.30-3.74, p = 0.0034) and post-operative DVT/PE (OR 2.45, 95% CI 1.09-5.51, p = 0.0303) were significantly associated with HIT. Our analysis did not show any differences in the incidence of vascular complications, post-op stroke/TIA, hemorrhage requiring transfusion and acute kidney injury between HIT and non-HIT group. The HIT group stayed longer in the hospital (30 vs 27 days, p &lt; 0.0001) and incurred higher total hospital charges ($695,834 vs. $640,089 p &lt; 0.0001). Conclusion: Among patients undergoing LVAD implants, HIT was associated with higher risk of in-hospital mortality, post-op DVT/PE, higher hospital charges and longer hospital stay.
Abstract 12832: Yield From Family Screening in a National Adolescent Cardiac Screening Program
Authors: Mark Abela, Jessica Debattista, Jeanesse Scerri, KENTARO YAMAGATA, Felice Tiziana, Melanie R Zammit Burg, Mark A Sammut, Robert G Xuereb, Victor Grech, Christian Scerri, lorenzo I monserrat, Michael Papadakis
Journal: Circulation (2021)

Introduction: Cascade family screening in inherited heart disease is often reserved for probands with a clinical diagnosis. This study assessed the yield of family screening in a national cardiac screening program, comparing a clinical and a clinical/genetic screening algorithm. Methods: 2708 teens (14-16 years) participated in a national cardiac screening program. Probands with suspected or confirmed inherited cardiac disease were evaluated clinically and genetically (216 cardiac gene panel). Relatives were subjected to a standard clinical screening protocol. Segregation analysis (Sanger sequencing) was performed in families with gene positive (G+) probands (VUS, likely or definite pathogenic mutations as per ACMJ criteria). Cascade screening was limited to a) first degree relatives and/or b) G+ individuals in the presence or absence (not exceeding two generations) of a clinical phenotype. A standard clinical algorithm (family screening in probands with a pre-clinical or clinical diagnosis) was compared with a genetic lead algorithm. Results: 2(0.1%) probands were diagnosed with a cardiac phenotype (n=1 HCM, n=1 LQTS). Another 17(0.6%) probands had evidence of pre-clinical disease. 81 relatives (60.5% female) underwent evaluation, mean age 41.1±16.7 at first evaluation. 11 families (57.9%) were G+. 54(66.7%) were first degree relatives. 12(14.2%) were screened because of a phenotype in the proband, 57(70.4%) because of a pre-clinical ECG. Another 12(14.8%) were screened because of the family genotype, translating into a 7.4% higher referral rate. The diagnostic yield was higher in the presence of a proband phenotype (41.7% vs 4.3%, p=0.001). Using a standard clinical algorithm, the diagnostic yield of family screening was 10.1% (n=2 HCM, n=5 LQTS). Adding genetics to the algorithm identified another individual (n=1 DCM), equating to a mildly decreased overall yield of 9.9%. The yield between both algorithms was not significantly different (p=0.956). Conclusion: The yield of family screening in probands with a pre-clinical phenotype or clinical diagnosis was 10.1%. This was similar (9.9%) when incorporating genetic testing in the algorithm. The added benefit of systematic genetic testing in a family screening program is limited.
IMMU-27. LONG TERM STABILIZATION OF RECURRENT HIGH-GRADE GLIOMA WITH PD-1 INHIBITOR PEMBROLIZUMAB IN TWO CASES
Authors: Matthew Moldenhauer, Steven Du, Dan Fu, Joon Myung, Daniela Bota, Xiao-Tang Kong
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Despite PD-1 inhibition having success in many cancers, it has uncertain effects in brain tumors. We report two cases of recurrent high-grade gliomas that have remained stable for over one year since starting pembrolizumab. CASE REPORTS Case 1: A 59-year-old male was diagnosed with glioblastoma (GBM) without MGMT methylation or IDH mutation in late 2018 after surgery. He received radiation and temozolomide (TMZ) followed by adjuvant TMZ before tumor progression. He underwent second tumor debulking with recurrent GBM on pathology with negative PD-L1 expression. He started carboplatin. Progression was noticed after 7 to 8 cycles. Pembrolizumab was added. Tumor was stabilized. Carboplatin was completed after total 12 cycles and the patient has continued single agent of pembrolizumab for more than one year with stable brain MRIs. The patient has survived for 24 months since recurrence and 30 months since diagnosis. Case 2: A 53-year-old male had a brain tumor discovered on MRI in 2012 and received no treatment until resection in 2014. In 2016, he underwent second tumor debulking and was diagnosed with anaplastic oligodendroglioma with negative PD-L1 expression. He received radiation followed by PCV regimen. 17 months since diagnosis, he had first tumor progression on PCV. TMZ was started. 22 months since diagnosis, bevacizumab was initiated due to further growth. 33 months since diagnosis, pembrolizumab was added due to new lesions after 12-months of bevacizumab therapy. His tumor was stabilized. Bevacizumab was eventually discontinued. He has continued single agent pembrolizumab for 6 months so far. His tumor has been stable for 22 months since starting pembrolizumab. Survival has been 38 months from first recurrence and 7 years since tissue diagnosis. DISCUSSION These cases demonstrate the potential effects of anti-PD-1 immunotherapy in stabilizing recurrent high-grade glioma with combination of other treatment agents followed by single agent as maintenance therapy.
Abstract 13906: Excess Epicardial Fat Volume is a Novel Risk Marker for Cardiovascular Disease Risk Assessment, Beyond Coronary Artery Calcium Score
Authors: Mahfouz El Shahawy, Katelyn Schultz, Sukanya Mohan, Antonella Sabatini, Genevieve Palmer
Journal: Circulation (2021)

Introduction: Excess epicardial fat volume (EFV) is reported to be associated with cardiovascular structural and functional abnormalities. Hypothesis: The purpose of this study is to assess whether excess EFV is associated with structural and functional changes, regardless of coronary artery calcium score (CACS). Methods: 2,892 untreated and asymptomatic subjects were screened for cardiovascular risk using the Early Cardiovascular Health Risk Scoring System (ECVHRS). The ECVHRS consists of 10 tests; 7 of which are vascular, and 3 are cardiac. The vascular tests are as follows: large (C1) and small (C2) artery stiffness, blood pressure (BP) at rest and post-mild exercise protocol (PME), carotid intima-media thickness (CIMT), abdominal aorta ultrasound, retinal photography, and microalbuminuria. The mild exercise protocol involves a 3-minute walk on a treadmill at 7% elevation and a speed of 2.5 miles per hour. The BP was measured at rest and immediately after completion of the 3-minute walk. An abnormal rise in BP-PME is defined as a systolic BP rise of ≥ 30 mmHg, a systolic BP ≥ 170 mmHg, or a diastolic BP ≥ 90 mmHg. The 3 cardiac tests are as follows: pro-BNP, electrocardiogram (ECG), and left ventricle ultrasound (LVUS). The ECG and LVUS were individually interpreted for abnormalities. Out of these 2,892 subjects, 328 were evaluated for CACS and EFV using a cardiac CT scan. Results: As seen in the table below, the subjects in Group 1 (n=35), with an excess amount of epicardial fat (EFV ≥ 94 cm 3 ) averaging 151.63 cm 3 , were associated with statistically significant structural and functional abnormalities, as compared with Group 2 (n=22), with a normal average EFV of 70.77 cm 3 . Conclusions: Based on our data, we posit that it is time to think beyond CACS as the mainstay determining factor for CVD risk. In our study population, EFV has a greater influence and correlation with cardiac structural and functional abnormalities. Time to focus on assessing EFV on cardiac CT scan.
Sphingosine‐1‐phosphate promotes tumor development and liver fibrosis in mouse model of congestive hepatopathy
Authors: Hironari Kawai, Yosuke Osawa, Michitaka Matsuda, Tomoyuki Tsunoda, Keisuke Yanagida, Daisuke Hishikawa, Miku Okawara, Yuzuru Sakamoto, Tomonari Shimagaki, Yuriko Tsutsui, Yuichi Yoshida, Shiori Yoshikawa, Kana Hashi, Hiroyoshi Doi, Taizo Mori, Taiji Yamazoe, Sachiyo Yoshio, Masaya Sugiyama, Daisuke Okuzaki, Haruki Komatsu, Ayano Inui, Miwa Tamura‐Nakano, Chinatsu Oyama, Hideo Shindou, Hironori Kusano, Masayoshi Kage, Toru Ikegami, Katsuhiko Yanaga, Tatsuya Kanto
Journal: Hepatology (2021)

Abstract Background and Aims Chronic liver congestion reflecting right‐sided heart failure (RHF), Budd‐Chiari syndrome, or Fontan‐associated liver disease (FALD) is involved in liver fibrosis and HCC. However, molecular mechanisms of fibrosis and HCC in chronic liver congestion remain poorly understood. Approach and Results Here, we first demonstrated that chronic liver congestion promoted HCC and metastatic liver tumor growth using murine model of chronic liver congestion by partial inferior vena cava ligation (pIVCL). As the initial step triggering HCC promotion and fibrosis, gut‐derived lipopolysaccharide (LPS) appeared to induce LSECs capillarization in mice and in vitro. LSEC capillarization was also confirmed in patients with FALD. Mitogenic factor, sphingosine‐1‐phosphate (S1P), was increased in congestive liver and expression of sphingosine kinase 1, a major synthetase of S1P, was increased in capillarized LSECs after pIVCL. Inhibition of S1P receptor (S1PR) 1 (Ex26) and S1PR2 (JTE013) mitigated HCC development and liver fibrosis, respectively. Antimicrobial treatment lowered portal blood LPS concentration, LSEC capillarization, and liver S1P concentration accompanied by reduction of HCC development and fibrosis in the congestive liver. Conclusions In conclusion, chronic liver congestion promotes HCC development and liver fibrosis by S1P production from LPS‐induced capillarized LSECs. Careful treatment of both RHF and liver cancer might be necessary for patients with RHF with primary or metastatic liver cancer.