tbuckley/cabot-search huggingface dataset:
Maria: Accurate Prediction of MHC-II Peptide Presentation with Deep-Learning and Lymphoma Patient MHC-II Ligandome
Authors: Binbin Chen, Michael Khodadoust, Niclas Olsson, Ethan Fast, Lisa E Wagar, Chih Long Liu, Mark Davis, Ronald Levy, Joshua E Elias, Russ B Altman, Arash A. Alizadeh
Journal: Blood (2017)
Adjuvant Low-dose Statin Use after Radical Prostatectomy: The PRO-STAT Randomized Clinical Trial
Authors: In Gab Jeong, Bumjin Lim, Sung-Cheol Yun, Ju Hyun Lim, Jun Hyuk Hong, Choung-Soo Kim
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Statin use is reportedly associated with the risk of prostate cancer, outcomes after treatment, and prostate cancer-specific mortality. We sought to determine the efficacy of adjuvant atorvastatin in prostate cancer after radical prostatectomy. Patients and Methods: In this randomized, double-blind trial, we assigned patients with pathologic high-risk prostate cancer to receive either low-dose atorvastatin (20 mg/day, n = 183) or placebo (n = 181) for 1 year after radical prostatectomy. The primary endpoint was the 1-year biochemical recurrence rate. The secondary endpoints included the 5-year biochemical recurrence-free survival and changes in lipid, testosterone, and sex hormone binding globulin levels. Results: From October 2012 through January 2019, a total of 364 patients underwent randomization. Among 59 total primary end points, 30 (16.4%) and 29 (16.0%) occurred in the atorvastatin and placebo groups, respectively. Atorvastatin did not significantly reduce the primary endpoint of 1-year biochemical recurrence [HR, 0.96; 95% confidence interval (CI), 0.58–1.60]. During a median follow-up of 24 months, 131 patients experienced biochemical recurrence (68 in the atorvastatin group and 63 in the placebo group), representing Kaplan–Meier estimated event rates of 24.0% and 25.4% in the atorvastatin and placebo groups, respectively, at 24 months (HR, 1.00; 95% CI, 0.71–1.41). We observed no significant between-group differences in the testosterone and sex hormone binding globulin levels. Conclusions: Among patients with high-risk pathologic features after radical prostatectomy for prostate cancer, 1-year adjuvant use of atorvastatin was not associated with a lower risk of disease recurrence compared with that for placebo. (ClinicalTrials.gov number, NCT01759836). See related commentary by Murtola and Siltari, p. 4947
Abstract 13590: Demographic and Clinical Characteristics of Patients With Obstructive Hypertrophic Cardiomyopathy in a Large, Nationwide Us Cohort
Authors: Michael Butzner, Phil Sarocco, Ethan J Rowin, Martin S Maron, Laura A Robertson
Journal: Circulation (2020)

Background: Obstructive hypertrophic cardiomyopathy (oHCM) has mostly been studied in patients treated in advanced comprehensive Centers of Excellence (COE). Understanding the true prevalence of patients with oHCM in the general US population may improve the screening, identification, and treatment outside of COEs. Objectives: To describe the demographics and clinical characteristics of patients with oHCM. Methods: This is a retrospective cohort study to assess patient-level data from the IBM Explorys database (observational period: January 1, 2010 to December 31, 2018). The Explorys database amassed electronic medical records from 39 Integrated Delivery Networks (IDN) from ~12,982,704 patients. We identified adult patients (&gt;18 years old) with oHCM and report their demographics and clinical characteristics from index date to the end of study period. Results: Of 8,792 patients, 53.0% were female, and 81.2% Caucasian (mean index age: 61.8 years). Primary insurance type was private (58.9%); 54.9% of patients lived in the Midwest. Mean BMI at index was 30.4; 30.9% were nondrinkers. The mean Quan-Charlson Comorbidity Index was 6.35% with the most common comorbidities being congestive heart failure (31.9%), chronic pulmonary disease (20.1%), and diabetes without chronic complications (16.9%). CV drug rates included β-blockers (80.5%), CCBs (46.0%), ACE inhibitors (27.7%), ARBs (18.8%), disopyramide (2.4%) and amiodarone (13.0%). Surgical procedure rates included septal myectomy (22%), ablation (19.8%), implantable cardioverter defibrillator (11.2%), and heart transplantation (0.3%). Major residual side effects subsequent to surgical procedures included atrial fibrillation (31.4%) and reintervention (15.6%). Common reintervention procedures included ablation and septal myectomy. Conclusions: This is the first study to examine a national sample of oHCM patients using clinical data from more than 39 IDNs. Leveraging the Explorys database allowed us to analyze a larger, more diverse cohort of oHCM patients across the entire broader US. The results from this analysis may be used to compare the characteristics of patients with oHCM in the general population with those treated in COE.
DOWN-REGULATION OF HYPOXIA INDUCIBLE FACTOR-1_(HIF-1_) EXPRESSION, THROUGH MTOR PATHWAY, BY LETROZOLE IN ER plus VE BREAST CANCER PATIENTS: CLINICAL IMPLICATIONS
Authors: C M Foroni, S Fox, A Berruti, L Dogliotti, A Bottini, A Harris, D G Generali
Journal: Annals of Oncology (2009)
Correction of the pathogenic mutation in TGM1 gene by adenine base editing in mutant embryos
Authors: Lu Dang, Xueliang Zhou, Xiufang Zhong, Wenxia Yu, Shisheng Huang, Hanyan Liu, Yuanyuan Chen, Wuwen Zhang, Lihua Yuan, Lei Li, Xingxu Huang, Guanglei Li, Jianqiao Liu, Guoqing Tong
Journal: Molecular Therapy (2021)

A couple diagnosed as carriers for lamellar ichthyosis, an autosomal recessive rare disease, encountered two pregnancy losses. Their blood samples showed the same heterozygous c.607C>T mutation in the TGM1 gene. However, we found that about 98.4% of the sperm had mutations, suggesting possible de novo germline mutation. To explore the probability of correcting this mutation, we used two different adenine base editors (ABEs) combined with related truncated single guide RNA (sgRNA) to repair the pathogenic mutation in mutant zygotes. Our results showed that the editing efficiency was 73.8% for ABEmax-NG combined with 20-bp-length sgRNA and 78.7% for Sc-ABEmax combined with 19-bp-length sgRNA. The whole-genome sequencing (WGS) and deep sequencing analysis demonstrated precise DNA editing. This study reveals the possibility of correcting the genetic mutation in embryos with the ABE system. A couple diagnosed as carriers for lamellar ichthyosis, an autosomal recessive rare disease, encountered two pregnancy losses. Their blood samples showed the same heterozygous c.607C>T mutation in the TGM1 gene. However, we found that about 98.4% of the sperm had mutations, suggesting possible de novo germline mutation. To explore the probability of correcting this mutation, we used two different adenine base editors (ABEs) combined with related truncated single guide RNA (sgRNA) to repair the pathogenic mutation in mutant zygotes. Our results showed that the editing efficiency was 73.8% for ABEmax-NG combined with 20-bp-length sgRNA and 78.7% for Sc-ABEmax combined with 19-bp-length sgRNA. The whole-genome sequencing (WGS) and deep sequencing analysis demonstrated precise DNA editing. This study reveals the possibility of correcting the genetic mutation in embryos with the ABE system.
Abstract 16531: Patient With Left Ventricular Assist Device Presents in Asystole
Authors: Emrie Tomaiko, Emrie Tomaiko, Wilber Su, J Peter Weiss, Anantharam Kalya, Radha Gopalan, Michael Zawaneh
Journal: Circulation (2020)

Introduction: Left Ventricular Assist Devices (LVAD) are becoming more common in the treatment of advanced heart failure. Patients with LVADs can present with life threatening sequelae of heart failure such as sustained VT and VF. Despite frequent documented presentations with ventricular arrhythmias in this patient population, presenting with ventricular asystole in patients with LVADs has not been previously described. We present a patient with LVAD, and without ICD, who presented in ventricular asystole. Case Report: A 67-year-old male with a history of ischemic cardiomyopathy and Heartmate III LVAD implanted one year prior to presentation as destination therapy presented to our facility complaining of three weeks of fatigue, dizziness with four days of nausea and emesis. He was noted to have an electrocardiogram (ECG) demonstrating artifact associated with the LVAD, however without discernible ventricular activity (Figure 1). Multiple ECGs and cardiac monitor tracings failed to demonstrate ventricular electrical activity, concerning for fine VF versus asystole. Transthoracic Echocardiogram (TTE) demonstrated bi-ventricular standstill. The patient was started on inotropes with Dobutamine then underwent Right Heart Catheterization (RHC). Catheter-induced ventricular potentials were repeatedly recorded, favoring asystole due to complete heart block (CHB) over fine VF. The patient underwent dual chamber ICD implant to allow ventricular pacing, which resulted in hemodynamic improvement. Conclusions: There have been several case reports which mentioned patients surviving fatal arrhythmias with an LVAD. To our knowledge, none have described hemodynamic stability with asystole due to CHB as the presenting rhythm. The incidence of conduction disease and arrhythmia in this patient population may indicate necessity of ICD implantation prior to LVAD implant.
Abstract 12602: Poor Quality of Life in Patients With and Without Frailty: Co-prevalence and Prognostic Implications in Patients Undergoing Percutaneous Coronary Interventions and Cardiac Catheterization
Authors: Amrit Kanwar, Veronique L Roger, Ryan J Lennon, Shahyar Gharacholou, Mandeep Singh
Journal: Circulation (2020)

Introduction: Relationship of QOL and frailty are poorly defined. Hypothesis: To study the prevalence and prognosis of poor QOL in frail patients. Methods: Predismissal standardized tests for frailty and QOL in 2 cohorts were administered. In cohort 1, 629 patients ≥ 65 years underwent percutaneous coronary intervention (PCI) from 2005-2008, frailty (Fried) and QOL [SF-36 and SAQ] were ascertained. Cohort 2 [921 patients, 535 PCI, ≥55 years] underwent cardiac catheterization from 2014-18, frailty (Rockwood) and QOL (Likert) were determined. Results: In cohort 1, 19%; and 20% in cohort 2 were frail. Lower median SAQ (58.9 vs. 82.2); physical (29.5 vs. 43.9) and mental (49.2 vs. 57.4) scores of SF-36 in cohort 1 higher rates of fair/poor health (56% vs 18%) in cohort 2 (all comparisons, p&lt;0.001) was seen in frail patients. As compared to without, frail patients were 5 times more likely (59% vs. 11%, p&lt;0.001) in cohort 1 and 7 times more likely (56% vs. 8%) in cohort 2 to have poor QOL. Adjusted three year all-cause death and death/myocardial infarction (MI) was significantly higher for patients undergoing PCI with frailty; [HR (95% CI) death, 4.20 (2.63, 6.68) and death or MI HR 2.72 (1.91, 3.87), p&lt;0.001) and with poor QOL [HR death 2.47 (1.59, 3.84) and death or MI 1.61 (1.16, 2.24) p&lt;0.001). There was no significant interaction between frailty and QOL (p=0.64) indicating their independent prognostic influence. Conclusions: Poor QOL is commonly seen with frailty. Both frailty and poor QOL had significant and independent association with long-term survival.
Abstract 11320: Inactivation of Serca2 Redox Cysteine 674 Promotes Pulmonary Artery Remodeling by Activating Ire1Á-xbp1 Pathway
Authors: Weimin Yu
Journal: Circulation (2019)

Introduction: Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) is a key enzyme for maintaining Ca2+ homeostasis in vasculature. The decrease of SERCA2a (one of SERCA2 subtypes) is related ...
Abstract 15602: A Massive Prosthetic Aortic Valve Dilemma
Authors: Minakshi Biswas, Zachary Graham, Luisa Mestroni
Journal: Circulation (2019)

Background: Prosthetic aortic valve (PAV) thromboses and vegetations have previously been described. We detail a case of a PAV mass, the consequences, and a therapeutic dilemma. Case: A 38-year-old...
Front-Line Treatment in Immune Thrombocytopenia Using Eltrombopag and High-Doses of Dexamethasone, Long-Term Follow-up
Authors: Olga Cantu Rodriguez, Miguel Herrera-Rojas, Andrea Garza-Acosta, Cesar Homero Gutierrez Aguirre, Perla Rocio Colunga Pedraza, Jose Jaime, Guillermo Jose Ruiz-Argüelles, David Gomez-Almaguer
Journal: Blood (2017)
Abstract 15766: Implantable Cardioverter-Defibrillator Therapy in Arrhythmogenic Right Ventricular Cardiomyopathy: long-term single centre experience.
Authors: Alessandro Blandino, Cristina Gallo, Matteo Anselmino, Carla Giustetto, Mara Morello, Elisabetta Toso, Salvatore Miceli, Lucia Garberoglio, Fiorenzo Gaita
Journal: Circulation (2010)

Introduction: ARVC is a heart-muscle disease characterized by progressive fibrofatty substitution leading to heart failure (HF) and sudden cardiac death (SCD). In this setting whether to implant an ICD is a pivotal decision. Hypothesis: evaluate long-term prognosis of ARVC patients who underwent ICD implantation to determine clinical predictors of appropriate ICD discharges. Methods: Twenty-two patients (16 men, 73%) with ARVC diagnosis (1994 Task Force Criteria) underwent ICD implantation. Sixteen (73%) patients were implanted in secondary prevention (3 for aborted SCD and 13 for sustained ventricular tachycardia (SVT) despite drug therapy) and 6 (27%) in primary prevention (3 for family history of SCD, 2 for inducibility of ventricular arrhythmias with hemodynamic compromise and 1 for biventricular HF). Appropriate interventions (AI) were considered: anti-tachycardia pacing on SVT; internal shock on SVT or VF. Internal shock triggered by supraventricular tachyarrhythmias or device malfunction was record...
Abstract 13412: Electronic Consultation for the Management of Atrial Fibrillation is Associated With Higher Healthcare Costs
Authors: Evan S Manning, Melanie D Whittington, Susan R Kirsh, Rachael Kenney, Jeffrey ToddStenberg, David H Au, Michael Ho, Joseph Simonetti
Journal: Circulation (2020)

Introduction: A study of 42,000 cardiology consults within the Veterans Health Administration (VHA) in 2016 found that patients who received electronic consultation (e-consults) had similar healthcare costs at 6 months compared to those who received face-to-face (F2F) consults. However, results may have been confounded if patients with less costly conditions received e-consults. Our aim was to compare costs between those receiving F2F vs. e-consults for a similar indication. Hypothesis: Electronic rather than F2F consultation for atrial fibrillation (AF) management will be associated with lower total healthcare costs. Methods: We conducted a retrospective cohort study of a national sample of VHA patients who received cardiology consultation in 2016. We used a natural language processing script to identify consults for AF management. Primary outcomes were total healthcare costs at 3 and 6 months. Secondary outcomes included inpatient and outpatient costs. We compared costs between groups using a generalized linear model with a gamma distribution and log link. We adjusted for community wage and Charlson comorbidity indices, distance to nearest facility, age, and gender. Standard errors were clustered at the facility level. Results: We sampled 176 F2F and 136 e-consults from 43 facilities. Mean total 6-month costs were $12,928 (95% confidence interval [CI]: 1,377; 40,644) and $8,286 (95% CI: 959; 31,320) among e-consult and F2F groups, respectively. The e-consult group had 12.3% higher 3-month (p&lt;0.001) and 41.5% higher 6-month total healthcare costs (p&lt;0.001) in comparison to the F2F group. At 3 months, the e-consult group had 25.1% lower inpatient costs (p&lt;0.001) and 32.5% higher outpatient costs (p&lt;0.001). At 6 months, the e-consult group had 6.3% higher inpatient costs (p&lt;0.001) and 48.4% higher outpatient costs (p&lt;0.001). Conclusions: Use of e-consults for AF management is associated with reduced inpatient costs at 3 months, but higher total costs, which were largely driven by outpatient costs. Improving our understanding of healthcare utilization after initial consultation, or in differences in reasons for consultation within AF management may help explain these differences.
Abstract 15205: MANP: A Novel ANP Analog for Hypertension Associated With Obesity and Metabolic Syndrome
Authors: Paul M McKie, Seethalakshmi R Iyer, Christopher Scott, Kent Bailey, Bradley K Johnson, Sherry L Benike, Horng Chen, Wayne L Miller, Riccardo Volpi, Aderville Cabassi, John C BURNETT, Valentina Cannone
Journal: Circulation (2020)

Introduction: Atrial natriuretic peptide (ANP) plays an important role in blood pressure (BP) regulation via the second messenger cGMP. ANP also induces lipolysis by increasing plasma levels of non-esterified fatty acids (NEFA). MANP is a new Mayo Clinic designed ANP analog consisting of the native ANP with a novel 12-amino-acid C-terminus extension. In experimental models, MANP is more potent than ANP in reducing BP and inducing natriuresis. These actions are mediated by the activation of the pGC-A receptor and generation of cGMP. To date, the BP pressure lowering, cGMP generating and lipolytic actions of MANP remain unexplored along with its safety and tolerability in subjects with hypertension (HTN) associated with metabolic disease. Hypothesis: In subjects with HTN, obesity and metabolic syndrome (MS), MANP administration is safe, well tolerated, activates cGMP and exerts BP lowering and lipolytic properties. Methods: Double-blind, placebo-control clinical trial in 22 subjects (17 receiving MANP) with HTN, obesity and MS involving a single subcutaneous (SQ) injection of MANP (2.5 μg/Kg) or placebo. Subjects were monitored and cardiovascular, cGMP and metabolic parameters were collected during 24 hours after the injection. Results: In all subjects, MANP was safe and well-tolerated with no serious adverse side effects. MANP increased mean cGMP plasma levels after 30 minutes (delta: 4.8 ± 2.0 pmol/mL, p=0.02) and 1 hour (delta: 2.9 ±1.3 pmol/mL, p=0.03) when compared to baseline. Six hours after MANP injection systolic BP decreased by 5.7 ± 2.9 mmHg (p=0.06) whereas subjects receiving placebo had no decrease in blood pressure values compared to baseline. During fasting period, one hour after the administration of MANP, NEFA plasma levels increased by 108.2 ± 37.4 μM (p=0.01). Conclusions: In subjects with HTN, obesity and MS, SQ MANP is safe, well tolerated and activates the pGC-A receptor as measured by a significant increase in the second messenger cGMP. Subjects receiving MANP showed a borderline significant decrease in systolic BP and a significant increase in NEFA circulating levels supporting anti-hypertensive and lipolytic properties. Our findings support MANP as a potential novel therapy for HTN associated with metabolic disease.
Abstract 15777: Induction Immunosuppression is Associated With a Lower Incidence of Post-transplant Diabetes Mellitus in Heart Transplant Recipients: A Propensity-adjusted Analysis
Authors: Suruchi K Gupta, Elizabeth Mostofsky, Wenyuan Li, Ali Hage, Shweta R Motiwala, Murray A Murray Mittleman
Journal: Circulation (2020)

Introduction: Post-transplant diabetes mellitus (PTDM) is a common complication among heart transplant recipients resulting in heightened risk of diabetes-related complications and death. While there is evidence that certain maintenance immunosuppression drugs like tacrolimus increase the risk of PTDM, it is not known whether induction immunosuppression does the same. We therefore evaluated whether induction immunosuppression in the early post-transplant period with IL-2 inhibitors, alemtuzumab or anti-thymocyte globulin is associated with PTDM after accounting for potential confounding by indication. Methods: Using data from the Scientific Registry of Transplant Recipients, we conducted a cohort study of 23,946 US adults who received a heart transplant in January 2008-December 2018. PTDM was defined as new diagnosis of diabetes at any time 6 months after transplant. We excluded patients with prior organ transplants and diabetes. We used logistic regression to construct propensity scores for predictors of induction immunosuppression and risk factors for PTDM including demographic, clinical and immunologic factors, pre-transplant therapies, steroids, functional status, and transplant year. We estimated the effect of induction immunosuppression in propensity-adjusted Cox proportional hazards models and produced fully adjusted Kaplan-Meier curves using inverse probability of treatment weights. Results: The average age was 54 (SD=12.5) years, 26% were female and 12,303 (51%) received induction immunosuppression. Over 84,969 person-years, 2,678 (11%) developed PTDM (32 cases/1,000 person-years). In the propensity-adjusted analysis, induction immunosuppression was associated with a 20% lower rate of PTDM (Figure 1; hazard ratio=0.80, 95% confidence interval 0.74-0.87). Conclusions: Adult heart transplant recipients who received induction immunosuppression had a 20% lower rate of PTDM compared to those who did not receive it.
Green-colored areas in laterally spreading tumors on narrow-band imaging: a future target for artificial-intelligence-assisted detection of malignancies?
Authors: Pierre Lafeuille, Tanguy Fenouil, Adrien Bartoli, Clara Yzet, Thomas Lambin, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2021)

Accurate real-time characterization of colorectal lesions during endoscopy is crucial for histological prediction, allowing the choice of the most appropriate treatment [1]. Polyps are characterized on the basis of an evaluation of their macroscopic appearance, vascular pattern, and pit pattern with magnification, under both white-light and virtual chromoendoscopy such as narrow-band imaging (NBI) [2]. However, colorectal lesions are not homogeneous: a malignant component can sometimes occupy only a small area of the whole lesion and be relatively difficult to detect, especially for inexperienced endoscopists.
Abstract 15578: <i>Propionibacterium Acnes</i> -associated Cardiac Sarcoidosis Presenting as Constrictive Pericarditis
Authors: Marysa Leya, Ike Okwuosa, Jon W Lomasney, Vera H Rigolin, Amit Pawale, Mugurel V Bazavan, Peter Sporn, Anjan Tibrewala
Journal: Circulation (2020)

Sarcoidosis is an antigen-mediated chronic multisystem inflammatory disease characterized by the formation of non-caseating epithelioid granulomas that disrupt tissue architecture, trigger fibrosis, and precipitate organ dysfunction. Cardiac involvement portends a poorer prognosis, presenting with conduction disease, heart failure, pulmonary hypertension, valvular disease, pericardial effusions, tamponade, ventricular arrhythmias, and sudden death. A 75-year-old man with a history of heart failure with mildly reduced ejection fraction, suspected ocular sarcoidosis, monoclonal gammopathy of uncertain significance and 6 months of exertional dyspnea and lower extremity edema presented with acute-on-chronic volume overload. His labs were notable for elevated inflammatory markers. Cardiac MRI showed pericardial thickening, complex pericardial fluid. The differential diagnosis included tamponade, restrictive cardiomyopathy or constrictive pericarditis secondary to paraproteinemia, viral/idiopathic, vasculitis, tuberculosis, lupus, or sarcoidosis. Simultaneous right and left heart catheterization was consistent with constriction. The patient underwent surgical pericardiectomy. The pathology was consistent with sarcoidosis and intraoperative cultures grew Propionibacterium acnes. This case reviews the mechanism and diagnosis of sarcoidosis, the diagnosis of constrictive pericarditis, and a possible role for P. acnes in the development of sarcoidosis. Constrictive pericarditis is a rare presentation of cardiac sarcoidosis, particularly when the only other suspected involvement of sarcoidosis is uveitis. P. acnes has been associated with granuloma formation in sarcoid, although the mechanism is still unknown. P. acnes may represent a potential therapeutic target once a mechanism is further elucidated.
静脈閉塞のため対側より左室リードの留置を必要とした両室ペースメーカ機能付除細動器(CRTD)の一例
Authors: 黒柳享義, 清野正典, 虎渓則孝, 中原志朗, 田中数彦, 酒井良彦, 高柳寛
Journal: Circulation (2007)