tbuckley/cabot-search huggingface dataset:
Abstract 14063: Circulating Levels of Collagen Formation and Degradation Biomarkers Are Prognostic for Risk of Hospitalization and Mortality in Patients With HFpEF - Results From the TRAINING-HF Cohort
Authors: Alexander Reese Petersen, Patricia Palau, Eloy Dominguez, Morten Karsdal, Federica Genovese, Julio Nunez
Journal: Circulation (2020)

Introduction: heart failure with preserved ejection fraction (HFpEF) is projected to become the dominant form of heart failure, and currently there are no viable treatment options to reduce mortality. Extracellular matrix turnover plays an important role in the pathology of heart failure. Our aim was to evaluate the association between adverse outcome in patients with HFpEF and circulating levels of novel collagen formation and degradation biomarkers in samples from HFpEF patients. Methods: fifty-nine symptomatic HFpEF patients were included for analysis. Biomarkers of formation of type III, VI, VIII, XXVIII collagens (PRO-C3, PRO-C6, PRO-C8 and PRO-C28) and degradation of type I, III and IV collagens (C1M, C3M and C4M) were assessed in baseline serum by means of competitive ELISA. Three models were generated by logistic regression with forward selection in relation to readmission and mortality, with the aim of assessing prognostic abilities for either outcome. The models were compared head to head using ROC curve analyses. Model 1 (CONF): age, sex, HDL, LDL, systolic blood pressure, diabetes status, BMI and smoking status. Model 2 (FORM): collagen formation biomarkers. Model 3 (DEGR): collagen degradation biomarkers. Results: all three models significantly predicted readmission (CONF: P&lt;0.0001, FORM: P=0.0029, DEGR: P=0.0026). For mortality, CONF and FORM were significantly predictive, while DEGR was borderline significant (CONF: P=0.0097, FORM: P&lt;0.0001, DEGR: P=0.059). ROC curves for mortality showed a significant difference between FORM and CONF (P=0.017), while no significant difference was seen when comparing CONF and DEGR. The CONF model was mainly driven by LDL (P=0.02) in relation to readmission, whereas no CONF variables were significant for mortality. No variables in the FORM or DEGR models were independently significant for readmission, but PRO-C6 and PRO-C8 were significant in the FORM model in relation to mortality (both P=0.028). Conclusion: in stable symptomatic HFpEF patients, turnover of collagen predicts outcome. Moreover, formation of collagens provides significant information on risk, suggesting a potential role for collagen biomarkers in stratifying HFpEF patients at higher risk of adverse outcomes.
Abstract 15444: Anticoagulation Treatment of Venous Thromboembolism Across the Weight Spectrum: Insights From the Veterans Health Administration
Authors: Alexander C Perino, Jun Fan, Mitra Kothari, ATIF MOHAMMAD, Patrick Hlavacek, Gail D Wygant, Susan K Schmitt, Krishna Pundi, Paul A Heidenreich, Jennifer Guo, Mintu Turakhia
Journal: Circulation (2020)

Introduction: In seminal trials of venous thromboembolism (VTE) treatment with direct oral anticoagulants (DOAC), few patients were enrolled at low and high body weights to estimate treatment effects in these subgroups. Consensus statements have recommended against use of DOACs in VTE for patients ≥120 kg. We sought to describe real-world use of DOACs and other anticoagulants for VTE across the weight spectrum. Methods: We performed a retrospective cohort study of patients with first-time VTE that were treated with anticoagulants in the VA health care system from 2008 to 2018. We excluded patients with 1) additional indications for anticoagulation (atrial fibrillation and mechanical valves) and 2) no documented weight in the 90 days prior to 90 days after index VTE. We stratified patients by weight (&lt;60, 60 to 119, ≥120 kg) and determined 1) index anticoagulation prescription in the 30 days after index VTE (DOAC, warfarin, and low molecular weight heparin or fondaparinux [LMWH/F] only) and 2) variables associated with DOAC prescription, as compared to warfarin, in those ≥120 kg. Results: After excluding 3,676 patients with missing weight, there were 111,774 patients with VTE (64±13 years, 6% female). The most common therapy was warfarin (66%), followed by DOAC (21%), and LMWH/F only (13%). Median weight was 92 kg (interquartile range: 28), with 13,753 patients (12%) with weight ≥120 kg. Across weight categories, proportion of patients receiving DOAC was similar. In patients ≥120 kg, after multivariate adjustment, multiple comorbidities were associated with warfarin prescription while chronic kidney disease was associated with DOAC prescription ( Table ). Conclusion: Weight ≥120 kg is common for VTE patients, with DOAC frequently prescribed despite consensus statements recommending DOAC avoidance. For patients ≥120 kg, comorbidities influence VTE treatment selection, and determination of optimal treatment strategies across the spectrum of comorbidities is needed.
MRE combined with FIB-4 (MEFIB) index in detection of candidates for pharmacological treatment of NASH-related fibrosis
Authors: Jinho Jung, Rohan R Loomba, Kento Imajo, Egbert Madamba, Sanil Gandhi, Ricki Bettencourt, Seema Singh, Carolyn Hernandez, Mark A Valasek, Cynthia Behling, Lisa Richards, Katie Fowler, Claude B Sirlin, Atsushi Nakajima, Rohit Loomba
Journal: Gut (2020)

Patients with non-alcoholic fatty liver disease (NAFLD) with ≥stage 2 fibrosis are at increased risk for liver-related mortality and are candidates for pharmacological therapies for treatment of NAFLD. The aim of this prospective cohort study is to examine the diagnostic accuracy of MR elastography (MRE) combined with fibrosis-4 (FIB-4) in diagnosing ≥stage 2 fibrosis (candidates for pharmacological therapies).This is a cross-sectional analysis of a prospective cohort (University of California at San Diego (UCSD)-NAFLD) including 238 consecutive patients with contemporaneous MRE and biopsy-proven NAFLD. Non-alcoholic steatohepatitis-Clinical Research Network-Histologic Scoring System was used to assess histology. The radiologist and pathologist were blinded to clinical, pathological and imaging data, respectively. Receiver operating characteristics (ROCs) were determined to examine the diagnostic accuracy of MRE and FIB-4 for diagnosis of ≥stage 2 fibrosis in NAFLD. We then validated these findings in an independent validation cohort derived from Yokohama City University in Japan (Japan-NAFLD Cohort; N=222 patients).In the UCSD-NAFLD (training) Cohort, MRE demonstrated a clinically significant diagnostic accuracy for the detection of ≥stage 2 fibrosis with an area under the ROC curve (AUROC) of 0.93 (95% CI 0.90 to 0.97) vs FIB-4 with an AUROC of 0.78 (95% CI 0.71 to 0.85), which was both clinically and statistically significant (p<0.0001). We then combined MRE with FIB-4 (MRE ≥3.3 kPa and FIB-4 ≥1.6) to develop a clinical prediction rule to rule in ≥stage 2 fibrosis patients which had positive predictive value (PPV) of 97.1% (p<0.02) in the UCSD-NAFLD cohort (AUROC of 0.90 (95% CI 0.85 to 0.95)) which remained significant at PPV of 91.0% (p<0.003) in the Japan-NAFLD Cohort (AUROC of 0.84 (95% CI 0.78 to 0.89)).MRE combined with FIB-4 (MEFIB) index may be used for non-invasive identification of candidates for (≥stage 2 fibrosis) pharmacological therapy among patients with NAFLD with a high PPV.
COVID-19 Outbreak Associated with a 10-Day Motorcycle Rally in a Neighboring State — Minnesota, August–September 2020
Authors: Melanie J. Firestone, Haley Wienkes, Jacob Garfin, Xiong Wang, Kelley Vilen, Kirk E. Smith, Stacy Holzbauer, Matthew Plumb, Kelly Pung, Carlota Medus, Joseph D. Yao, Matthew J. Binnicker, Andrew C. Nelson, Sophia Yohe, Kathryn Como-Sabetti, Kris Ehresmann, Ruth Lynfield, Richard Danila
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

During August 7-16, 2020, a motorcycle rally was held in western South Dakota that attracted approximately 460,000 persons from across the United States to numerous indoor and outdoor events over a 10-day period.During August-September 2020, the Minnesota Department of Health (MDH) investigated a coronavirus disease 2019 (COVID-19) outbreak associated with the rally in Minnesota residents.Fifty-one primary event-associated cases were identified, and 35 secondary or tertiary cases occurred among household, social, and workplace contacts, for a total of 86 cases; four patients were hospitalized, and one died.Approximately one third (34%) of 87 counties in Minnesota had at least one primary, secondary, or tertiary case associated with this rally.Genomic sequencing supported the associations with the motorcycle rally.These findings support current recommendations for mask use, physical distancing, reducing the number of attendees at gatherings, isolation for patients with COVID-19, and quarantine for close contacts to slow the spread of SARS-CoV-2 (1).Furthermore, although these findings did not capture the impact of the motorcycle rally on residents of other states, they demonstrate the rationale for consistent mitigation measures across states.
メラノーマ分化関連遺伝子-5(MDA-5)の過剰発現:エンテロウイルス(EV)感染の新しいマーカー
Authors: Ukimura Akira, Iimori Akio, Shimomura Hiroaki, Kitaura Yasushi, Suma Hisayoshi
Journal: Circulation (2008)
Abstract 15632: Phenotypic Overlap Between Left Ventricular Noncompaction and Hypertrophic Cardiomyopathy: A Case Report
Authors: Ethan Senser, Madison Hawkins, Eric M Williams, Lauren Gilstrap
Journal: Circulation (2020)

Introduction: Left ventricular non-compaction (LVNC) is characterized by extensively trabeculaed myocardium adjacent to normal compacted myocardium of the left ventricle (LV). Hypertrophic cardiomyopathy (HCM) typically appears as diffuse or segmental LV hypertrophy, with or without outflow tract obstruction. Cardiac sarcomere mutations are present in most HCM cases and have also been identified in LVNC. Whether or not there is clinically significant phenotypic overlap between the two diseases is less well understood. We present a case of known HCM that met criteria for both LVNC and HCM by cardiac MRI. Case: A 49-year old man with HCM due to a c.3742_3759dup variant in MYBPC3 presented to clinic after an episode of syncope and ICD firing. In clinic, the device was interrogated and he was found to have had ventricular flutter which was successfully treated with one shock and a new, high (&gt;20%) burden of premature ventricular beats. An echocardiogram showed a stable ejection fraction at 42%, mild concentric LV hypertrophy without obstruction and a newly dilated LV with an end diastolic diameter of 7.1cm (previously 6.2cm). A cardiac MRI was performed ( Figure ) and showed LV noncompaction and diffuse transmural and mid myocardial hyperenhancement/fibrosis of the septum, basilar lateral wall, anterior wall, and distal right ventricle consistent with patient's long-standing history of hypertrophic cardiomyopathy. Discussion: This case highlights the phenotypic overlap between HCM and LVNC by cardiac MRI. Had this patient not already carried a genetic diagnosis of HCM, he would likely have been diagnosed with LVNC based on this cardiac MRI. The phenotypic overlap in these diseases raises questions about ICD guidelines, the role of anticoagulation and prognosis.
Abstract 13781: Recurrence of Papillary Fibroelastoma
Authors: Ahmed Sorour, Reto Kurmann, Edward El-Am, Melanie Bois, Christopher Scott, Alexander Lee, Joseph A Dearani, Joseph J Maleszewski, Kyle W Klarich
Journal: Circulation (2020)

Background: Papillary fibroelastoma (PFE) is the most common benign cardiac tumor. Because PFEs have the potential to embolize, they typically are surgically excised. Prior studies have suggested that postoperative recurrence of PFE is rare or does not occur. Objectives: To determine the rate at which PFEs recurred after surgical removal and to identify any risk factors associated with recurrence. Methods: Patients with pathologically proven PFE were retrospectively identified from a single center. Patients were included in the study if they had an echocardiographic examination at least 1 year after surgery. Echocardiographic images obtained intraoperatively (after excision) and at dismissal were compared with those of the most recent examination to assess the possibility of PFE recurrence. Results: Ninety eight patients were identified. The mean (SD) duration of follow-up was 5.4 (3.7) years (range, 1-17 years). Twelve patients (12.2%) had echocardiographically proven PFE recurrence. Three patients had the recurrent lesion surgically re-excised, and pathologic analysis showed that 2 were recurrent PFEs and 1 was a Lambl excrescence. Clinical presentation of stroke or TIA was more common for the recurrence patients (for the first PFE) than for the nonrecurrence patients (83% vs 26%; P &lt;.001). Conclusions: Contrary to published data, PFEs do recur after surgical excision. This emphasizes the importance of postoperative follow-up with transesophageal echocardiography for identifying recurrent masses. Table. Characteristics of Patients With Recurrent PFE Abbreviations: AV, aortic valve; LA, left atrium; LE, Lambl excrescence; LVOT, left ventricular outflow tract; MV, mitral valve; PV, pulmonary valve; RA, right atrium; RC, right cusp; TV, tricuspid valve. a Corresponds to the same location. b Corresponds to a different location .
Abstract 16374: Effect of Dapagliflozin According to Duration of Heart Failure: An Analysis of the DAPA-HF Trial
Authors: Su E Yeoh, Kieran Docherty, Silvio E Inzucchi, Lars Kober, Mikhail Kosiborod, Anna Maria Langkilde, Feilpe A Martinez, Olof Bengtsson, Piotr Ponikowski, Marc S Sabatine, Mikaela SjÃ¶strand, Scott Solomon, Pardeep S Jhund, John J McMurray
Journal: Circulation (2020)

Introduction: The relationship between duration of heart failure (HF), patient characteristics, outcomes, and the effect of treatment is largely unknown. We investigated these questions in DAPA-HF. Hypothesis: We hypothesized that longer HF duration is associated with worse outcomes and that, compared with placebo, the benefit of the SGLT2 inhibitor, dapagliflozin, is consistent, irrespective of HF duration, in patients with HF and reduced ejection fraction (HFrEF). Methods: HF duration was categorised as 0-1, &gt;1-2, &gt;2-5 and &gt;5 years. Outcomes were adjusted for prognostic variables and analysed using Cox regression. The primary endpoint was the composite of worsening HF or cardiovascular death. Treatment effect (dapagliflozin versus placebo) was examined within each duration category and by duration threshold. Results: The number patients in each category was: 1098 (0-1 year), 686 (&gt;1-2 years), 1105 (&gt;2-5 years) and 1855 (&gt;5 years). Patients with longer-duration HF were older and more comorbid with worse quality of life. The primary outcome rate (per 100 person-years) increased with HF duration: 10.2 (95% CI 8.7-12.0) for the 0-1-year group, 10.6 (8.7-12.9) for &gt;1-2 years, 15.5 (13.6-17.7) for &gt;2-5 years and 15.9 (14.5-17.6) for &gt;5 years. The adjusted hazard ratio was 0.98 (95% CI 0.75-1.27), 1.52 (1.22-1.89) and 1.60 (1.31-1.96) respectively, for &gt;1-2, &gt;2-5 and &gt;5 years compared with 0-1 years. Similar trends were seen for all other outcomes. The benefit of dapagliflozin was consistent across HF duration for all outcomes and on threshold analysis (Figure). Conclusion: Patients with longer-duration HF had higher rates of worsening HF and death. The benefit of dapagliflozin was consistent irrespective of HF duration. Starting dapagliflozin has substantial benefits, even in patients with longstanding HFrEF.
Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial
Authors: Renaud Felten, Valérie Devauchelle-Pensec, Raphaèle Seror, Pierre Duffau, David Saadoun, Eric Hachulla, Hatron Pierre Yves, Carine Salliot, Aleth Perdriger, Jacques Morel, Arsène Mékinian, Olivier Vittecoq, Jean-Marie Berthelot, Emanuelle Dernis, Veronique Le Guern, Philippe Dieudé, Claire Larroche, Christophe Richez, Thierry Martin, Charles Zarnitsky, Gilles Blaison, Pierre Kieffer, François Maurier, Azeddine Dellal, Stephanie Rist, Emmanuel Andres, Anne Contis, Emmanuel Chatelus, Christelle Sordet, Jean Sibilia, Cécile Arnold, Mira Y Tawk, Ouafaa Aberkane, Lise Holterbach, Patrice Cacoub, Alain Saraux, Xavier Mariette, Nicolas Meyer, Jacques-Eric Gottenberg
Journal: Annals of the Rheumatic Diseases (2020)

Objectives No immunomodulatory drug has been approved for primary Sjögren’s syndrome, a systemic autoimmune disease affecting 0.1% of the population. To demonstrate the efficacy of targeting interleukin 6 receptor in patients with Sjögren’s syndrome-related systemic complications. Methods Multicentre double-blind randomised placebo-controlled trial between 24 July 2013 and 16 July 2018, with a follow-up of 44 weeks, involving 17 referral centres. Inclusion criteria were primary Sjögren’s syndrome according to American European Consensus Group criteria and score ≥5 for the EULAR Sjögren’s Syndrome Disease activity Index (ESSDAI, score of systemic complications). Patients were randomised to receive either 6 monthly infusions of tocilizumab or placebo. The primary endpoint was response to treatment at week 24. Response to treatment was defined by the combination of (1) a decrease of at least 3 points in the ESSDAI, (2) no occurrence of moderate or severe activity in any new domain of the ESSDAI and (3) lack of worsening in physician’s global assessment on a Visual Numeric Scale ≥1/10, all as compared with enrolment. Results 110 patients were randomised, 55 patients to tocilizumab (mean (SD) age: 50.9 (12.4) years; women: 98.2%) and 55 patients to placebo (54.8 (10.7) years; 90.9%). At 24 weeks, the proportion of patients meeting the primary endpoint was 52.7% (29/55) in the tocilizumab group and 63.6% (35/55) in the placebo group, for a difference of −11.4% (95% credible interval −30.6 to 9.0) (Pr[Toc &gt;Pla]=0.14). Conclusion Among patients with primary Sjögren’s syndrome, the use of tocilizumab did not improve systemic involvement and symptoms over 24 weeks of treatment compared with placebo. Trial registration number NCT01782235 .
Abstract 13532: Comparison of Inferior Vena Cava and Subclavian Vein Collapsibility Index by Ultrasound for Determination of Relative Intravascular Volume in Acute Decompensated Heart Failure
Authors: Yvonne E Kaptein, Pedro D Salinas, Payal Sharma, Ana Christina Perez Moreno, Nasir Sulemanjee, M. Fuad Jan
Journal: Circulation (2020)

Introduction: Accurate assessment of relative intravascular volume is needed to guide management of acute decompensated heart failure (ADHF). Current assessments include history and physical examination (specific but not sensitive), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (sensitive but not specific).Ultrasound (US) of inferior vena cava (IVC) collapsibility with respiration is commonly used to assess intravascular volume and right atrial pressure (RAP) but may be technically challenging. US of subclavian vein (SCV) collapsibility may provide an alternative assessment. Hypothesis: In ADHF, SCV collapsibility index (CI) may correlate with IVC CI and RAP. Methods: Prospective study of non-ventilated patients with ADHF who had NT-proBNP within 24 hours of paired IVC and SCV diameter measurements by US. Results: Forty-two patients (median age 66.5 years, 45% female, and 64% white) were enrolled, with 52 encounters. Cardiovascular comorbidities included hypertension (93%), chronic kidney disease (64%), coronary artery disease (55%), atrial fibrillation/flutter (55%), and valvular disease (55%). Of 38 patients with known heart failure, 63% had HFrEF, 16% HFmrEF, and 21% HFpEF.Correlation of paired IVC CI and SCV CI with relaxed breathing was R = 0.65 (N = 36). Correlation of paired IVC CI and SCV CI with forced inhalation was R = 0.47 (N = 36). Log 10 NT-proBNP was inversely correlated with IVC CI (R = -0.35; N = 51) and SCV CI (R = -0.33; N = 36). For patients with right heart catheterization within 24 hours of US, correlation of RAP to IVC CI was R = -0.53 (N = 9), and RAP to SCV CI was R = -0.65 (N = 9). Moderate or severe tricuspid regurgitation decreased CI independently of intravascular volume and RAP (figure). Conclusions: US measurements of SCV CI correlate well with paired IVC CI in non-ventilated ADHF. RAP by RHC correlated better with SCV CI than with IVC CI. SCV CI may be a reliable alternative to IVC CI in assessing relative intravascular volume.
Investigation of Suicidality and Psychological Adverse Events in Patients Treated With Finasteride
Authors: David-Dan Nguyen, Maya Marchese, Eugene B. Cone, Marco Paciotti, Shehzad Basaria, Naeem Bhojani, Quoc-Dien Trinh
Journal: JAMA Dermatology (2020)

There is ongoing controversy about the adverse events of finasteride, a drug used in the management of alopecia and benign prostatic hyperplasia (BPH). In 2012, reports started emerging on men who had used finasteride and either attempted or completed suicide.To investigate the association of suicidality (ideation, attempt, and completed suicide) and psychological adverse events (depression and anxiety) with finasteride use.This pharmacovigilance case-noncase study used disproportionality analysis (case-noncase design) to detect signals of adverse reaction of interest reported with finasteride in VigiBase, the World Health Organization's global database of individual case safety reports. To explore the strength of association, the reporting odds ratio (ROR), a surrogate measure of association used in disproportionality analysis, was used. Extensive sensitivity analyses included stratifying by indication (BPH and alopecia) and age (≤45 and >45 years); comparing finasteride signals with those of drugs with different mechanisms but used for similar indications (minoxidil for alopecia and tamsulosin hydrochloride for BPH); comparing finasteride with a drug with a similar mechanism of action and adverse event profile (dutasteride); and comparing reports of suicidality before and after 2012. Data were obtained in June 2019 and analyzed from January 25 to February 28, 2020.Reported finasteride use.Suicidality and psychological adverse events.VigiBase contained 356 reports of suicidality and 2926 reports of psychological adverse events (total of 3282 adverse events of interest) in finasteride users (3206 male [98.9%]; 615 of 868 [70.9%] with data available aged 18-44 years). A significant disproportionality signal for suicidality (ROR, 1.63; 95% CI, 1.47-1.81) and psychological adverse events (ROR, 4.33; 95% CI, 4.17-4.49) in finasteride was identified. In sensitivity analyses, younger patients (ROR, 3.47; 95% CI, 2.90-4.15) and those with alopecia (ROR, 2.06; 95% CI, 1.81-2.34) had significant disproportionality signals for increased suicidality; such signals were not detected in older patients with BPH. Sensitivity analyses also showed that the reports of these adverse events significantly increased after 2012 (ROR, 2.13; 95% CI, 1.91-2.39).In this pharmacovigilance case-noncase study, significant RORs of suicidality and psychological adverse events were associated with finasteride use in patients younger than 45 years who used finasteride for alopecia. The sensitivity analyses suggest that these disproportional signals of adverse events may be due to stimulated reporting and/or younger patients being more vulnerable to finasteride's adverse effects.