tbuckley/cabot-search huggingface dataset:
Complement activity is regulated in C3 glomerulopathy by IgG–factor H fusion proteins with and without properdin targeting domains
Authors: Alyssa C. Gilmore, Yuchun Zhang, H. Terence Cook, Deborah P. Lavin, Suresh Katti, Yi Wang, Krista K. Johnson, SungKwon Kim, Matthew C. Pickering
Journal: Kidney International (2020)

C3 glomerulopathy is characterized by accumulation of complement C3 within glomeruli. Causes include, but are not limited to, abnormalities in factor H, the major negative regulator of the complement alternative pathway. Factor H-deficient (Cfh-/-) mice develop C3 glomerulopathy together with a reduction in plasma C3 levels. Using this model, we assessed the efficacy of two fusion proteins containing the factor H alternative pathway regulatory domains (FH1-5) linked to either a non-targeting mouse immunoglobulin (IgG-FH1-5) or to an anti-mouse properdin antibody (Anti-P-FH1-5). Both proteins increased plasma C3 and reduced glomerular C3 deposition to an equivalent extent, suggesting that properdin-targeting was not required for FH1-5 to alter C3 activation in either plasma or glomeruli. Following IgG-FH1-5 administration, plasma C3 levels temporally correlated with changes in factor B levels whereas plasma C5 levels correlated with changes in plasma properdin levels. Notably, the increases in plasma C5 and properdin levels persisted for longer than the increases in C3 and factor B. In Cfh-/- mice IgG-FH1-5 reduced kidney injury during accelerated serum nephrotoxic nephritis. Thus, our data demonstrate that IgG-FH1-5 restored circulating alternative pathway activity and reduced glomerular C3 deposition in Cfh-/- mice and that plasma properdin levels are a sensitive marker of C5 convertase activity in factor H deficiency. The immunoglobulin conjugated FH1-5 protein, through its comparatively long plasma half-life, may be a potential therapy for C3 glomerulopathy.
Cytopenia Management in Patients With Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax Plus Azacitidine in the VIALE-A Study
Authors: Keith W. Pratz, Courtney D. DiNardo, Dominik Selleslag, Junmin Li, Kazuhito Yamamoto, Marina Konopleva, Andrew McDonald, Sunil Babu, Don A. Stevens, Hagop M. Kantarjian, Fabiola Traina, Adriano Venditti, Jiri Mayer, Melissa Montez, Giridharan Ramsingh, Huan Jin, William Ainsworth, Yinghui Duan, Anders Erik Svensson, Michael Werner, Jalaja Potluri, Brian A Jonas
Journal: Blood (2020)
Screening for High Blood Pressure in Children and Adolescents
Authors: Alex H. Krist, Karina W. Davidson, Carol M. Mangione, Michael J. Barry, Michael Cabana, Aaron B. Caughey, Katrina Donahue, Chyke A. Doubeni, John W. Epling, Martha Kubik, Gbenga Ogedegbe, Lori Pbert, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2020)

<h3>Importance</h3> Prevalence of hypertension (both primary and secondary) in children and adolescents in the US ranges from 3% to 4%. Primary hypertension in children and adolescents occurs primarily in children older than 13 years and has no known cause but is associated with several risk factors, including family history and higher body mass index. Secondary hypertension occurs primarily in younger children and is most commonly caused by genetic disorders, renal disease, endocrine disorders, or cardiovascular abnormalities. <h3>Objective</h3> To update its 2013 recommendation, the USPSTF commissioned a review of the evidence on the benefits and harms of screening, test accuracy, the effectiveness and harms of treatment, and the association between hypertension and markers of cardiovascular disease in childhood and adulthood. <h3>Population</h3> This recommendation statement applies to children and adolescents aged 3 to 18 years not known to have hypertension or who are asymptomatic. <h3>Evidence Assessment</h3> The USPSTF concludes that the evidence to support screening for high blood pressure in children and adolescents is insufficient and that the balance of benefits and harms cannot be determined. <h3>Recommendation</h3> The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for high blood pressure in children and adolescents. (I statement)
FRI0435 THE CLINICAL SIGNIFICANCE OF SERUM AUTOANTIBODIES AND HLA-B27 MOLECULE TESTING IN UYGUR PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION
Authors: X. Chen, L. Wu, X. Wu, C. N. Luo, Y. M. Shi
Journal: Annals of the Rheumatic Diseases (2020)

Background: AIDS is a deadly infectious disease caused by the HIV. When HIV infects a host, it may induce production of autoantibodies due to the structural antigen similarity between viral proteins and selfantigens.The molecular mimicry between HIV protein and self-antigens could cause antibody cross-reactions and lead to development of autoimmune disease. Objectives: To explore the clinical value of serum autoantibodies and human leukocyte antigen (HLA-B27) molecular testing in Uygur patients with human immunodeficiency virus (HIV) infection. Methods: A total of 727 HIV-infected Uygur patients who visited Kuche Infectious Diseases Hospital during May 2016 to March 2017 were include in this study. The other 390 healthy people were enrolled as controls. Serum antinuclear antibodies (ANA) and ANA Profile, anti-cyclic citrullinated peptide (CCP) antibody, and HLA-B27 molecule were tested. Results: Among 727 HIV-infected Uygur patients, 317 were males and 410 were females with mean age (35.52±13.44) years old. The mean duration of disease was (6.34±3.05)years. There were 697(95.87%) patients receiving Highly active antiretroviral therapy (HAART) with mean duration of treatment (6.34±3.05)years. Rheumatic manifestations were recorded in 238 (32.74%) HIV-infected Uygur patients, mainly with dry mouth and dry eye (15.41%), alopecia (9.90%), arthralgia (8.94%), ect. Compared with the health controls, positive ANA was more common in HIV infected Uygur patients (33.42% vs. 17.43%, P &lt; 0.001) with low titers (ANA titer:1:100). HIV-infected Uygur patients had higher positive anti-u1-RNP antibodies positive rate (1.10%), but lower anti-SSA antibodies positive rate (0.14%) and anti-CCP antibodies positive rate (0.28%). Patients with positive ANA in HAART group were significantly less than that in non-treatment group (38.72% vs. 50.00%, P =0.049).Only one female patient was HLA-B27 positive (0.14%), which was significantly lower than that in healthy controls (3.08%) ( P &lt;0.001). Also, only one patient was diagnosed with rheumatoid arthritis (RA). Conclusion: Rheumatic manifestations are common in HIV-infected Uygur patients. Several autoantibodies are positive, but the coincidence of rheumatic diseases is rare. It’s noted that patients with Rheumatic manifestations and low titre positive ANA should be considered as a differential diagnosis of HIV infection. Disclosure of Interests: None declared
Abstract 14242: Homogeneous Fetal Access to Cardiac Care in a Heterogeneous State
Authors: Laura Garcia Godoy, Erin J Madriago, christina ronai
Journal: Circulation (2020)

Introduction: Timely prenatal diagnosis of congenital heart disease (CHD) allows for families to participate in complex decisions and plan for the care of their child. This study sought to investigate if the timing of the first fetal echocardiogram (FE) and the characteristics of fetal counseling were impacted by parental socioeconomic factors. Hypothesis: We hypothesized that the scheduling of initial FE would be delayed due to distance from hospital, rurality of maternal home and median income. Methods: We performed a retrospective chart review of all fetal patients referred to our institution from 1/1/17 to 12/31/18 with a diagnosis of CHD. We looked at the gestational age at the first FE, age of mother, zip code of residence, rurality index, distance from our hospital and maternal ethnicity. Counseling was evaluated based on documentation in the FE report regarding use of interpreter, time billed for counseling, individuals accompanying mother, and treatment option chosen. Results: 138 maternal-fetal dyads met inclusion criteria, 29 dyads had a diagnosis of single ventricle heart disease. The median gestational age (GA) at first FE was 24 weeks 4 days. The median income was $57,019 ($42,624-$83,695), and the median distance to the hospital was 51 miles (3.2-379.9miles). There was no difference in income, distance from hospital or rurality index and timing of first FE. There was no significant difference between maternal ethnicity and age of mother, GA at initial FE, number of follow-up FEs or family accompanying mother to the visit. There was no difference in maternal ethnicity and use of interpreter with time counseled. Patients who lived in rural areas did have increased counseling time (p&lt;.05). Importantly, there was no difference between socioeconomic factors and ultimate parental choices (termination, palliative delivery or surgery). Conclusions: Oregon comprises a heterogeneous population from a large geographical catchment. While prenatal counseling and family decision making is multifaceted we demonstrated that dyads were referred from across the state and received care in a uniformly timely manner, and once at our center received consistent counseling despite differences in parental socioeconomic factors.
Abstract 14398: African Americans With Transthyretin Cardiac Amyloidosis Have a Lower Prevalence of Atrial Fibrillation but Increased Thromboembolic Events Than Caucasians
Authors: Lindsey R Mitrani, Silvia Vilches, Roberta Mussinelli, Francesco Salinaro, Jeffeny De Los Santos, Esther Gonzalez-Lopez, Angelo Giuseppe Caponetti, Giulia Saturi, Stefano Perlini, Claudio Rapezzi, Pablo Garcia-Pavia, Mathew S Maurer
Journal: Circulation (2020)

Background: African Americans (AA) have a higher rate of stroke and of stroke-related death compared with Caucasians (Cau). Paradoxically, atrial fibrillation (AF), a common cause of stroke, affects twice as many Cau compared with AA. Transthyretin cardiac amyloidosis (ATTR-CA) is commonly associated with AF and strokes. We hypothesized that AF race-related patterns in the general population would exist in patients with ATTR-CA with increased thromboembolic events in the AA population. Methods: Patients with ATTR-CA (n=615) at four international centers were retrospectively identified. We compared baseline characteristics, presence of atrial fibrillation, and outcomes of thromboembolic events (stroke, transient ischemic attack, and peripheral embolism) and major bleed between AA and Cau. Results: Of 615 patients, 545 (88.6%) identified as Cau, and 70 (11.4%) as AA. As shown in table 1, Cau patients were diagnosed with AF more often than AA (p &lt;0.01), while AA were younger and more often had ATTRv disease (p &lt;0.01). Both prevalent and incident thromboembolic events were more common in AA than Cau. Major bleeding was more prevalent at baseline for AA with no difference was shown in follow-up, though AA had more often labile INR (p&lt;0.01). AA more frequently had no anticoagulation compared with Cau (p&lt;0.01) Over a median of 26 months, 24 Cau (4.4%) had thromboembolic events compared with 10 (14.3%) AA (p &lt;0.01). Conclusions: These data suggest that while Cau with ATTR-CA more often have AF than AA, thromboembolic events are more common in the AA population. Whether these data relate to mechanism of disease or disparities in healthcare is yet to be determined
Abstract 16247: Methamphetamine Use Predicts Worse Prognosis in a Safety Net Heart Failure Population
Authors: Anjali B Thakkar, Yifei Ma, Teresa Wang, Alexandra Teng, Rebecca Scherzer, Priscilla Hsue
Journal: Circulation (2020)

Background: Methamphetamine (MA) use is rising, and overdose deaths have increased by 500% in San Francisco since 2008. MA use is associated with heart failure (HF); yet, cardiovascular (CV) outcomes in this population have not been described. Methods: We performed a retrospective case-control study of HF patients at a safety net hospital in San Francisco. Between January 2001-June 2019, 1771 HF patients with MA use were matched by age and gender to 3542 HF patients without MA use. We examined age and gender-adjusted associations of MA use with likelihood of index HF admission and 30-day readmission (HF and all-cause), and used demographic-adjusted Cox regression model with competing risks to compare hazard rates associated with MA use over the 18-year study period. Results: At time of HF diagnosis, mean age was 52 years and 77% were male. Patients with MA use were significantly more likely than non-MA users to be black (49.1% vs 33.0%), and to have comorbid conditions including HIV (14.5% vs 4.7%), pulmonary hypertension (11.1% vs 7.7%), hypertension (82.0% vs 77.6%), and cocaine use (58.0% vs 14.7%). Despite similar rates of coronary artery disease, myocardial infarction, and diabetes, HF patients with MA use were less likely to have percutaneous coronary intervention (6.1% vs 8.2%) or coronary artery bypass graft (0.8% vs 1.4%), p&lt;0.05 for all. Compared to HF patients without MA use, HF patients with MA use had higher rates of index HF hospitalizations (36.0% vs 21.7%, adjusted odds ratio 2.04, 95% CI 1.80-2.32, p&lt;0.01), 30-day HF readmission (12.2% vs 6.4%, adjusted hazard ratio (aHR) 1.87, 95% CI 1.31-2.67, p&lt;0.01) and 30-day all cause readmission (20.9% vs 14.3%, aHR 1.46, 95% CI 1.14-1.88, p&lt;0.01). Exposure to MA was associated with higher likelihood of death during the study period, regardless of hospitalizations (22.4% vs 15.1%, aHR=1.17, 95% CI 1.03-1.33, p&lt;0.01). Conclusions: In our study, HF patients with MA use were more likely to be admitted for an index HF admission; subsequently, they were also more likely to be readmitted within 30 days. Regardless of hospitalization risk, individuals with MA use had higher likelihood of death. Further study to understand the clinical and socioeconomic factors driving worse outcomes in this high-risk population is needed.
Does water immersion WASH in bowel scope?
Authors: Sauid Ishaq, Keith Siau, Sergio Cadoni
Journal: Gut (2020)

Rutter et al 1 should be congratulated on this first randomised controlled trial (RCT) comparing water-assisted sigmoidoscopy (WAS) versus carbon dioxide (CO2) insufflation in patients undergoing English Bowel Scope Screening (BSS). The authors reported no significant difference in the primary outcome of recalled pain, or in secondary outcomes of adenoma detection rate (ADR) between WAS and CO2 insufflation groups. Before we consider the study findings, we would like to discuss the following points with the esteemed authors of this study.

First, the WAS technique deserves mention. The authors used the water immersion (WI) technique to facilitate progression of scope with CO2 insufflation when required and the infused water was aspirated during withdrawal. The gold standard water exchange (WE) technique was not chosen for the study, which would have removed the infused water mainly during insertion without …
Abstract 15729: Effect of Metformin on Outcomes of Catheter Ablation for Atrial Fibrillation
Authors: Amrish Deshmukh, Elif Oral, Michael Ghannam, Jackson Liang, Mohammed Saeed, Ryan Cunnane, Hamid Ghanbari, Rakesh Latchamsetty, Thomas Crawford, Frank Bogun, Krit Jongnarangsin, Frank Pelosi, Aman Chugh, Fred Morady, Hakan Oral
Journal: Circulation (2020)

Background: Diabetes mellitus (DM) and glycemic control are risk factors for atrial fibrillation (AF). Metformin may have antifibrillatory properties by altering atrial metabolism. It is unknown whether metformin has favorable effects on the outcomes of catheter ablation (CA) for AF. Objective: To determine whether metformin use is associated with maintenance of sinus rhythm after CA for AF. Methods and Results: A 1 st CA was performed in 271 consecutive patients with DM and AF (age: 65±9 years, women: 34 %; and paroxysmal AF: 50%). A total of 182 (67%) patients were treated with metformin and 79/182 were also receiving other antidiabetics or insulin. HbA1c and preprocedural fasting blood glucose were similar among the patients treated with and without metformin (7.2±1.4% vs. 7.2±1.3%, P=0.95 and 162± 61 vs. 159±66 mg/dL, P=0.72). At a median of 10 months (IQR: 5-23, mean 15±13 months) after CA, 100/182 patients (55%) on metformin remained in sinus rhythm without concomitant antiarrhythmic drugs (AAD) compared to 36/89 patients (40%) not receiving metformin (P=0.03). On K-M analysis, patients on metformin were more likely to stay in sinus rhythm after CA, with or without AADs (P&lt;0.001, log-rank, Figure). On Cox proportional hazards analysis, adjusted for age, gender, BMI, type of AF(paroxysmal vs. non-paroxysmal), fasting blood glucose, AAD use, obstructive sleep apnea, chronic kidney disease, and left atrial diameter, metformin use was associated with a ~35% lower probability of recurrent atrial arrhythmia(HR: 0.65, ±95% CI: 0.44-0.97, P=0.04). Increase in left atrial diameter (per mm, HR: 1.05, ±95% CI:1.01-1.08, P=0.001) and non-paroxysmal AF (HR: 1.9, ±95% CI: 1.3-2.9, P=0.001) were associated with a higher risk of recurrence after CA of AF. Conclusion: In patients with DM, the use of metformin was associated with a significant reduction in recurrent atrial arrhythmias after CA for AF independent of the other risk factors, including preprocedural glycemic control.
Abstract 17109: Real World Assessment of Atrial Fibrillation and Other Arrhythmias After Cryptogenic Stroke
Authors: Naga Venkata K Pothineni, Uyanga Batnyam, Jeffrey Arkles, John Bullinga, Brett L CUCCHIARA, Sanjay Dixit, Epstein E Andrew, David S Frankel, Fermin C Garcia, Ramanan Kumareswaram, Jeffrey J Luebbert, Todd Mendelson, Steven Messé, Pasquale Santangeli, David Lin, Scott E Kasner, Francis E Marchlinski, Rajat Deo
Journal: Circulation (2020)

Introduction: Long-term monitoring for atrial fibrillation (AF) is recommended in patients, who have experienced a cryptogenic stroke (CS). Clinical trials have identified AF in ~30% of patients after 3 years of continuous monitoring with insertable cardiac monitors (ICMs). Hypothesis: In a real-world analysis from a large academic healthcare system, we sought to evaluate a CS population with ICMs and a) determine the yield of AF and subsequent initiation of anticoagulation; and b) identify the presence of other arrhythmias. Methods: We evaluated all CS patients who had received an ICM between October 2014 and April 2020. We manually reviewed all stored electrocardiograms that were automatically labeled as AF by the ICM and adjudicated them as either a) AF or b) other cardiac arrhythmia including premature atrial contractions (PAC), premature ventricular contractions (PVC), supraventricular tachycardia (SVT), or nonsustained ventricular tachycardia (NSVT). Results: A total of 84 CS patients with ICMs were included: 51% men, mean age 63 years, and mean CHA 2 DS 2 -VASc 4.1. Over a median follow-up duration of 15.7 months, there were 34 patients (40% of the cohort) who did not have any AF alerts. In the remaining 50 patients, there were 960 stored electrograms that were adjudicated. Only 154 recordings from 16 patients (19% of the entire cohort) were adjudicated as AF. Oral anticoagulation was initiated in all these patients with adjudicated AF. The remaining tracings, which had been automatically categorized by the ICM as AF alerts, represented 34 patients (40% of the cohort). These patients had other arrhythmias including frequent PACs or PVCs, SVT, or NSVT. Conclusions: Compared to clinical trials, our real-world assessment suggests that the yield of AF following CS is lower - approximately 20%. Our findings highlight the importance for reviewing device tracings given the high rates of false positive for AF. Further research to refine AF detection algorithms in ICMs is needed.
Abstract 13092: Regulation of SARS-CoV-2, Viral Entry Proteins ACE2 and TMPRSS2, and Interferon Genes by Host MicroRNAs
Authors: Jacob B Pierce, Viorel Simion, Basak Icli, Daniel Perez-Cremades, Henry Cheng, Mark W Feinberg
Journal: Circulation (2020)

Introduction: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can cause myocardial injury, heart failure, and death. MicroRNAs (miRNAs) have emerged as important regulators of viral pathogenesis, but the impact of host miRNAs on SARS-CoV-2 infectivity remains unknown. Hypothesis: Bioinformatic analysis of host miRNAs targeting the SARS-CoV-2 genome, viral entry proteins ACE2 and TMPRSS2, and their upstream regulators the interferons (IFNs) will reveal high-probability miRNAs that may regulate myocardial injury during SARS-CoV-2 infection. Methods: Using validated bioinformatic prediction algorithms, we generated a prioritized atlas of host miRNAs predicted to bind to SARS-CoV-2 genome, ACE2, TMPRSS2, and IFNs. We validated the biologic plausibility of these binding interactions by investigating their expression in established miRNA profiling datasets from cell lines susceptible or resistant to SARS-CoV-2 infection and in human tissue samples. Results: Phylogenetic analysis of 820 SARS-CoV-2 genomes revealed high homology and, after iterative filtering, 288 predicted binding miRNAs. Overlay of these miRNAs in susceptible and resistant cell lines identified miRNA binders to ORFs (miR-23a (1ab), miR-29a, -29c (1ab, N), miR-151a, -151b (S spike), miR-4707-3p (S spike), miR-298 (5’-UTR), miR-7851-3p (5’-UTR), miR-8075 (5’-UTR)) that may be important for viral infectivity. We also highlight miRNAs predicted to regulate critical host factors during infection including the receptor ACE2 3’-UTR (miR-9-5p, miR-218-5p), the serine protease TMPRSS2 3’-UTR (let-7d-5p, -7e-5p, miR-494-3p, miR-382-3p, miR-181c-5p), and the IFNs such as IFN-α 3’-UTR (miR-361-5p, miR-410-3p). Given the known roles for several of these miRNAs in cardiovascular injury (e.g. miR-23a, -29a, -29c, -494, and let-7), we discuss a framework for further interrogation of these miRNAs in patients and disease-based models. Conclusions: Overall, this study provides insight into potential novel regulatory mechanisms of SARS-CoV-2 by host miRNAs and lays the foundation for future investigation of these miRNAs as potential therapeutic targets or biomarkers for myocardial injury.
APCOLIS SCORE PREDICTS OUTCOME IN PATIENTS OF CIRRHOSIS WITH SARS-COV-2 INFECTION- DATA FROM ONGOING APASL COVID LIVER INJURY SPECTRUM (APCOLIS-I) STUDY
Authors: Subhan, Amna, Loho, Imelda M., Esmail, Eslam Saber, Payawal, Diana A., Alam, Mohd Shahinul, Chuang, Wan-Long, Anand, Lovkesh, Sharma, Manoj K., Omata, Masao, Sarin, Shiv Kumar, Apasl Covid Task, Force
Journal: Hepatology (2020)