tbuckley/cabot-search huggingface dataset:
AB0441 ASSOCIATION OF CO-POSITIVITY FOR ANTI-DSDNA, -NUCLEOSOME, AND -HISTONE ANTIBODIES AND DISEASE ACTIVITY IN PATIENTS WITH LUPUS NEPHRITIS: RESULTS FROM THE KORNET REGISTRY
Authors: D. J. Park, S. E. Choi, H. Xu, J. H. Kang, S. S. Lee
Journal: Annals of the Rheumatic Diseases (2020)

Background: Recent studies have shown that the simultaneous positivity of anti-double stranded DNA, -nucleosome, and -histone antibodies (3-pos) is prevalent in lupus nephritis (LN) patients compared to non-renal systemic lupus erythematosus (SLE) patients. Objectives: The aim of this study was to define the clinical, biologic, histopathologic, and prognostic differences according to the simultaneous reactivity to those antibodies in Korean patients with biopsy-proven LN. Methods: We studied 102 patients who underwent kidney biopsy prior to the start of induction treatment and who were subsequently treated with immunosuppressives and followed-up for more than 12 months. Sociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained by a review of patients’ charts. Antibodies were detected by immunoblot analysis or ELISA at the time of renal biopsy. Results: Fifty-eight (35.4%) of the total of 102 LN patients had 3-pos. In comparison with non-3-pos patients, the patients with 3-pos showed a higher SLE Disease Activity Index-2000 score (P=0.002), lower lymphocyte level (p=0.004), higher proportion of proteinuria &gt;3.5 g/24 hr (p=0.005), and higher positivity of urinary sediments (p=0.005) at the time of renal biopsy. In the renal histopathologic findings, the patients with 3-pos had more proliferative LN (p=0.015) and also showed more endocapillary hypercellularity, sub-endothelial hyaline deposits, fibrinoid necrosis/karyorrhexis, and cellular crescents in the disease activity index (p=0.016, p=0.045, p=0.002, and p=0.022, respectively), as well as a higher activity score (p=0.011). After a median follow-up of 83.2 months, rapid glomerular filtration rate decline was frequently observed in patients with 3-pos compared to those without (p=0.012). Conclusion: Our findings suggest that 3-pos is related to severe LN and, furthermore, that patients with 3-pos show a rapid decline of renal function compared to those without. Disclosure of Interests: None declared
Abstract 13928: Subclinical Myocardial Dysfunction With Coronavirus Disease 2019
Authors: Jordan B Strom, Lila M Martin, Sarah E Fostello, James D Chang, Connie W Tsao, Warren J Manning
Journal: Circulation (2020)

Background: Coronavirus disease 2019 (COVID-19) is associated with cardiac injury and overt myocardial dysfunction. However, whether COVID-19 is associated with subclinical myocardial dysfunction is unknown. Methods: We evaluated patients hospitalized for COVID-19 referred for transthoracic echocardiography (TTE), between March 17 and May 22, 2020, with a left ventricular ejection fraction (LVEF) ≥ 50%. Controls in a 1:1 ratio were selected from patients receiving TTE during the same month. Global longitudinal strain (GLS) was used to assess the association of COVID-19 and subclinical myocardial disease. Results: Among 99 patients (49 cases, 50 controls), average GLS was significantly reduced in cases vs. controls (mean ± SD, -14.8 ± 4.0% vs. -21.1 ± 4.0%, p &lt; 0.0001). A total of 82.8% of cases vs. 7.1% of controls had an average GLS below normal (&gt; 18%; p &lt; 0.0001), which persisted despite multivariable adjustment ( Table ). Among COVID-19 patients with a prior TTE, absolute average GLS decreased 3.2% (p = 0.008) despite no change in LVEF (p = 0.41). Average GLS was reduced in non-survivors compared with survivors (p = 0.04), though only septal wall thickness (p = 0.03) was associated with in-hospital mortality on multivariable analysis. Conclusions: Among hospitalized patients receiving TTE, COVID-19 is independently associated with subclinical left ventricular systolic dysfunction in the vast majority of patients, and subclinical LV dysfunction is associated with survival. The clinical implications of these findings should be evaluated in future longitudinal multicenter studies.
Abstract 14543: Diminished Aortic Flow in Fetus and Its Implications in Development of Aortic Coarctation and Arch Interruption: A 3d/4d Fetal Echocardiography and Computational Fluid Dynamics Study
Authors: Zhuo Chen, Hongkai Zhao, Ying Zhao, Jiancheng Han, Chi chi Do-Nguyen, Zhenglun Wei, Yihua He, Shuping Ge
Journal: Circulation (2020)

Background and Objectives: During critical windows of cardiac morphogenesis and remodeling, altered intrauterine hemodynamics may lead to congenital heart defects, such as aortic arch abnormalities. We sought to investigate the effects of diminished flow in the fetal aorta to understand the cause, improved diagnosis, and prognosis of coarctation of aorta (CoA) and interrupted aortic arch (IAA). Methods: Computational fluid dynamics (CFD) model of aortic and ductal arches was built based on dynamic 3D/4D spatiotemporal image correlation (STIC) fetal echocardiography (FE) and Doppler images from a normal fetus. Pulsatile hemodynamics, including velocity, pressure gradient, and wall shear stress (WSS), were stimulated as aortic flow decreased from 100% to 80%, 60%, 40%, and 20% by CFD, with accompanying ductal flow increased proportionally to maintain combined cardiac output (Figure). Results: As aortic flow diminished from 100% to 20% progressively, velocity, pressure, and WSS decreased in systole and diastole in aortic arch and isthmus. As aortic flow decreased, the flow structures changed, resulting in a reduction of WSS in the aortic isthmus, especially on the posterior wall. There was a “zero flow zone” between the left carotid and subclavian arteries when aortic flow decreased to 40% of baseline, and another one between innominate and left carotid arteries when it decreased to 20%. Pearson correlation analysis showed significant correlations between aortic flow, pressure, velocity, and WSS (r=0.883 - 1.000, P=0.047 - 0.001) at aortic isthmus. Conclusions: It is feasible to create a hemodynamic model of human fetal aortic arch using 3D/4D FE and CFD. The alterations of flow variables, especially WSS, and the “zero flow zones" in the aorta from progressive aortic flow reduction suggest the "flow-dependency” of the fetal aortic arch development and a unifying hypothesis of diminished flow in the pathogenesis of CoA and IAA.
Pharmacokinetic and Pharmacodynamic Head-to-Head Comparison of Clinical, Equivalent Doses of Insulin Glargine 300 units · mL−1 and Insulin Degludec 100 units · mL−1 in Type 1 Diabetes
Authors: Paola Lucidi, Paola Candeloro, Patrizia Cioli, Anna Marinelli Andreoli, Chiara Pascucci, Angela Gambelunghe, Geremia B. Bolli, Carmine G. Fanelli, Francesca Porcellati
Journal: Diabetes Care (2020)

To prove equivalence of individual, clinically titrated basal insulin doses of glargine 300 units ⋅ mL-1 (Gla-300) and degludec 100 units ⋅ mL-1 (Deg-100) under steady state conditions in a single-blind, randomized, crossover study, on the glucose pharmacodynamics (PD) in people with type 1 diabetes (T1D).Subjects with T1D (N = 22, 11 men, age 44.3 ± 12.4 years, disease duration 25.5 ± 11.7 years, A1C 7.07 ± 0.63% [53.7 ± 6.9 mmol ⋅ mL-1], BMI 22.5 ± 2.7 kg · m-2), naïve to Gla-300 and Deg-100, underwent 24-h euglycemic clamps with individual clinical doses of Gla-300 (0.34 ± 0.08 units ⋅ kg-1) and Deg-100 (0.26 ± 0.06 units ⋅ kg-1), dosing at 2000 h, after 3 months of optimal titration of basal (and bolus) insulin.At the end of 3 months, Gla-300 and Deg-100 reduced slightly and, similarly, A1C versus baseline. Clamp average plasma glucose (0-24 h) was euglycemic with both insulins. The area under curve of glucose infused (AUC-GIR[0-24 h]) was equivalent for the two insulins (ratio 1.04, 90% CI 0.91-1.18). Suppression of endogenous glucose production, free fatty acids, glycerol, and β-hydroxybutyrate was 9%, 14%, 14%, and 18% greater, respectively, with Gla-300 compared with Deg-100 during the first 12 h, while glucagon suppression was no different. Relative within-day PD variability was 23% lower with Gla-300 versus Deg-100 (ratio 0.77, 90% CI 0.63-0.92).In T1D, individualized, clinically titrated doses of Gla-300 and Deg-100 at steady state result in similar glycemic control and PD equivalence during euglycemic clamps. Clinical doses of Gla-300 compared with Deg-100 are higher and associated with quite similar even 24-h distribution of PD and antilipolytic effects.
Abstract 14255: Contemporary Characteristics and Management of Patients Aged ≥ 80 Years Presenting With Non-ST Elevation Myocardial Infarctions in the United States: A Nationwide Inpatient Sample Cohort Study
Authors: Efehi Igbinomwanhia, Alejandro Sanchez Nadales, Richard A Grimm, Brian P Griffin, Samir R Kapadia, Bo Xu
Journal: Circulation (2020)

Introduction: Improvements in primary prevention, medical therapies and interventions have coincided with a rapidly aging population across the globe. The contemporary characteristics and in-hospital outcomes of non-ST-elevation myocardial infarction (NSTEMI) among patients ≥ 80 years old in the United States (US) are not well studied. Methods: Adults (≥ 18) with a primary discharge diagnosis of NSTEMI were identified from the 2016 National Inpatient Sample. The exposure of interest was age ≥80 years, with a comparison group of those aged between 18 and 79 years. Results: Of 93,875 patients who had NSTEMI, 22,210 (23.65%) were ≥ 80 years. Among patients ≥ 80 years, 52.5% were female, 73.6% were Caucasians, with a significant proportion being managed by conservative therapy (73.4%). Patients ≥ 80 years were less likely to receive percutaneous coronary intervention (PCI) (adjusted odds ratio [aOR]: 0.49; 95% confidence intervals [CI]: 0.47-0.51) or coronary artery bypass graft surgery (CABG) (aOR: 0.28; 95% CI: 0.25-0.30) when compared to the younger group. Regardless of management strategy, patients ≥ 80 years old had higher inpatient mortality compared to younger patients. Patients ≥ 80 years undergoing PCI experienced more complete heart block, but not other complications, such as cardiogenic shock, cardiac arrest, and stroke, compared to the younger group (Table). NSTEMI patients ≥ 80 years who were managed conservatively or by CABG had a higher Elixhauser comorbidity index than patients undergoing PCI. Conclusions: A significant number of NSTEMI patients in the US were aged ≥ 80 years. Despite overall similar in-hospital complications profiles across management strategies, NSTEMI in patients ≥ 80 years was most often managed conservatively.
Radical changes will help NHS survive
Authors: Zosia Kmietowicz
Journal: BMJ (2000)

The NHS can deliver an improved service and meet more of patients' demands under the current system of tax funding, provided that certain radical changes are made, according to a report from the King's Fund, the independent healthcare charity.

The report calls for a new approach to planning in the NHS in which health professionals in hospitals and in the community take more responsibility for deciding how money should be spent.

“In the past, doctors have been reluctant to get involved in management …
Abstract 15473: Effect of Statins on Coronary Plaque Progression Assessed by Serial Coronary Computed Tomography Angiography
Authors: Suraj Dahal, Suvasini Lakshmanan, Khadije Ahmad, Vahid Rezvanizadeh, Ahmed K Ghanem, Afiachukwu G Onuegbu, Divya Birudaraju, April Kinninger, Ilana Golub, Sajad Hamal, Christopher Dailing, Fred Flores, Sion Roy, Matthew J Budoff
Journal: Circulation (2020)

Introduction: Statins stabilize coronary plaques and reduce clinical events. However, it is unclear how statins change the total plaque burden and plaque morphology. Hypothesis: We aimed at investigating whether statin users have less coronary plaque progression compared to non-statins users. Methods: We identified 243 subjects undergoing serial computed tomography angiography, 163 taking statins and 80 who are not. Coronary plaque (total, calcified, non-calcified including fibrous, fibrous-fatty and low-attenuation plaque (LAP)) volume was measured using semi-automated plaque software (Qangio, Medis) and its change overtime between statins users and non-statins users was evaluated using Analysis of Covariance (ANCOVA) modeling adjusted for age, gender, diabetic status, presence of hypertension, past smoking use, and baseline plaque levels. Results: Subjects on statin therapy had higher body mass index, were more likely to be diabetic, had hyperlipidemia, and were past smokers. Median coronary artery calcium score was significantly lower in the statin group; p&lt;0.034. Driven primarily by changes in fibrous plaque, those on statin therapy showed 25% less total plaque (P=0.013) and 31% less total non-calcified plaque (P=0.006) at follow-up than non-statin users. Conclusions: The current study indicates that statin use is associated with less progression of total plaque and total non-calcified plaque burden.
Abstract 14099: Beta-blockers Reduce Mortality in Patients With Heart Failure or Ischemic Heart Disease and Chronic Obstructive Pulmonary Disease
Authors: Mohammed Ruzieh, Aaron Baugh, lama jebbawi, Andrew J Foy
Journal: Circulation (2020)

Introduction: In patients with heart failure (HF) and ischemic heart disease (IHD), beta-blockers (BB) are associated with improved mortality. However, in patients with co-morbid chronic obstructive pulmonary disease (COPD), this drug class is less utilized due to concerns about an unfavorable impact on the morbidity and mortality. Patients with COPD and heart disease have higher mortality than those with heart disease alone. There is a need to clarify the safety of BB in this population. Objective: To assess the effect of BB therapy on mortality in patients with heart disease and COPD. Methods: We performed a systematic search of MEDLINE and PubMed inception until May 30, 2020 to identify articles of BB use in patients with COPD. The risk ratio (RR) of mortality with BB use was calculated using the Mantel Haenszel random effect model. Statistical analysis was performed using Review Manager Web (RevMan Web). A two-sided p value of &lt; 0.05 was considered statistically significant. Results: A total of 16 studies were included in this meta-analysis, comprising 133,538 patients (44,893 received BB, 88,381 received no control drug, and 264 received placebo). BB use was associated with reduced risk of mortality overall (14.8% vs. 19.9%, RR: 0.67, 95% CI: 0.57 - 0.79), in patients with IHD (18.6% vs. 26.6%, RR: 0.64, 95% CI: 0.50 - 0.82), and in patients with HF (8.1% vs. 23.6%, RR: 0.56, 95% CI: 0.41 - 0.75), Figure. BB were used to treat hypertension in one study, and it was associated with reduced risk of mortality (6.2% vs. 13.4%, RR: 0.46, 95% CI: 0.28 - 0.78). In contrast, βB use was not associated with statistically significant reduced risk of mortality when given without a specified cardiovascular indication (25.0% vs. 32.5%, RR: 0.82, 95% CI: 0.59 - 1.15), figure. Conclusion: Beta-blockers are associated with improved mortality in patients with HF or IHD and COPD. A diagnosis of COPD should not preclude treatment with beta-blockers, as previous concerns likely over-stated risk.
Abstract 12850: Isolated and Assisted Transcatheter Coil Embolization of Coronary Artery Lesions: The Cleveland Clinic Experience
Authors: Omar M Abdelfattah, Anas M Saad, Nicholas Kassis, Shashank Shekhar, Toshiaki Isogai, Mohamed M Gad, Keerat R Ahuja, Essa Hariri, Manpreet Kaur, Medhat Farwati, Jaikirshan Khatri, Amar Krishnaswamy, Samir R Kapadia
Journal: Circulation (2020)

Introduction: Transcatheter coil embolization (TCE) has been introduced as a modality in treating several coronary artery lesions including coronary artery fistula (CAF), patent left internal mammary artery (LIMA) side branch, coronary artery perforation (CAP), coronary artery aneurysm (CAA), and coronary artery pseudoaneurysm (CAPA) is limited. Hypothesis: TCE is underutilized in various coronary lesions despite its efficacy. Methods: This is a retrospective, descriptive study of all adult patients who underwent TCE at the Cleveland Clinic between August 2007 and August 2019. A total of 41 patients, including 25 CAF, 7 patent LIMA side branches, 5 CAP, 2 CAA, and 2 CAPA from a total of 121,196 cases, were studied. Results: Successful angiographic closure was performed in 37 out of 41 (90%) cases (100% ,100% ,100%, 88%, 80%, of patent LIMA side branch ,CAA, CAPA, CAF, CAP, respectively). Ampatzer vascular plug was used as an adjunctive device in 10% of the total cohort. No adverse events were directly associated with TCE among the LIMA, CAA, and CAPA lesions, and only one patient with CAF required re-intervention at three months due to coil migration. One patient with a large CAP of the mid-left anterior descending artery died while hospitalized due to cardiogenic shock despite successful embolization. Conclusions: Transcatheter Coil embolization in our institution was safe and effective in treating different coronary circulation abnormalities with successful angiographic results in 90% of treated cases. Additional study on the utilization of vascular plug devices in cases such as LIMA side branch or CAF would be beneficial to better understand the treatment options.
Use of the Glasgow-Blatchford score during the COVID-19 pandemic needs more rigorous research
Authors: Zhihui Duan, Shengyun Zhou, Zongxian Niu
Journal: Endoscopy (2020)

A very important paper by Young-II Kim et al. [1] was published recently in Endoscopy. The authors found that the Glasgow-Blatchford score (GBS) was inferior to the Rockall score in predicting the need for urgent hemostatic intervention for tumor-associated upper gastrointestinal bleeding (UGIB), leading to poor performance (area under the receiver operating characteristic curve [AUROC] 0.56). This study is crucial for patient risk stratification for UGIB during the COVID-19 pandemic, and we would like to draw your attention toward it.
Nanoscale platform for delivery of active IRINOX to combat pancreatic cancer
Authors: Fan Lei, Xinyuan Xi, Satyanarayana Rachagani, Parthasarathy Seshacharyulu, Geoffrey A. Talmon, Moorthy P. Ponnusamy, Surinder K. Batra, Tatiana K. Bronich
Journal: Journal of Controlled Release (2020)
Abstract 14232: The Cathepsin D-m6pr-erk1/2 Pathway Mediates Cellular Senescence and Osteogenic Activities in Human Aortic Valve Interstitial Cells
Authors: Qingzhou YAO, Erlinda The, Lihua Ao, Yufeng Zhai, David A Fullerton, Xianzhong Meng
Journal: Circulation (2020)

Background: Calcific aortic valve disease (CAVD) is one of the most prevalent cardiovascular disorders in the elderly, and aortic valve interstitial cells (AVICs) play a major role in valvular calcification associated with CAVD progression. Recent studies found that pharmacological or genetic clearance of senescent cells attenuates aortic valve calcification in animal models, indicating an important role of senescent cells in promoting valvular calcification. However, the mechanism underlying cellular senescence in aortic valves is unclear. Our pilot work found that greater densities of senescent cells in AVIC isolates from diseased human aortic valves are associated with elevated levels of matrilin 2 and cathepsin D in AVICs. We tested the hypothesis that matrilin 2 and cathepsin D mediate the senescence and osteogenic responses in human AVICs. Methods and Results: AVICs were isolated from normal and diseased aortic valves. Levels of P16 were assessed by immunoblotting, and senescent changes is examined using senescence-associated β-galactosidase (SA-β-gal) staining. AVICs from diseased valves displayed higher levels of P16 and greater SA-β-gal staining. Both recombinant human matrilin 2 (2.0 μg/ml) and recombinant human cathepsin D (40 nM) promoted P16 expression and enhanced SA-β-gal staining in normal AVICs, leading to greater calcium deposition. Knockdown of cathepsin D reduced matrilin-2-induced P16 expression, SA-β-gal staining and calcium deposition in normal AVICs. Moreover, recombinant cathepsin D activated the M6PR-ERK1/2 pathway in normal AVICs. Blocking or knockdown of M6PR (M6P, 10 mM or siRNA, 1.0 nM) or inhibition of ERK1/2 (PD98059, 25 μM) attenuated the effect of cathepsin D on AVIC senescent change and associated osteogenic activation. Conclusion: AVICs of aortic valves from patients with CAVD have higher levels of senescence activity. Cathepsin D mediates AVIC senescence and associated osteogenic activation through the M6PR-ERK1/2 pathway and is involved in the mechanism by which soluble matrilin 2 promotes cellular senescence and osteogenic activity in human AVICs. Targeting the cathepsin D-M6PR-ERK1/2 cascade may suppress AVIC senescence activity and attenuate aortic valve calcification.
Abstract 14518: Effects of 1-year of High Intensity Interval Training and Omega-3 Fatty Acid Supplementation in Stage A HFpEF: A Randomized Controlled Trial
Authors: Christopher M Hearon, Katrin Dias, Mitchel Samels, margot morris, Dean Palmer, Sheryl A Livingston, James P Macnamara, Benjamin D LEVINE, Satyam Sarma
Journal: Circulation (2020)

Background: There are no proven pharmacologic strategies for HFpEF; therefore, lifestyle interventions must be developed to prevent disease progression in those at high risk for developing HFpEF (Stage A). We performed a randomized, double blind, placebo controlled trial evaluating the effect of 1-year of high intensity interval training (HIIT) and polyunsaturated fatty acid supplementation (PUFA) on key risk factors in Stage A HFpEF. Hypothesis: Long duration (1-year) HIIT and PUFA (1.6g/daily Omega-3-Acid Ethyl Esters) will reduce visceral adiposity, improve aerobic fitness, and reverse vascular stiffness in middle-aged subjects with cardio-metabolic risk factors. Methods: Individuals with stage A HFpEF (n= 73; 40-55 years; BMI&gt;30 kg/m 2 ; visceral fat &gt; 2 kg; NT-proBNP&gt;40pg/ml or hscTnT&gt;3.0 pg/ml) were randomized to HIIT + PUFA (n=22)/placebo (n=24) or yoga + PUFA (n=15)/placebo (n=19). We assessed visceral fat (DEXA), aerobic fitness (VO 2 max), cardiac output (Q C , acetylene rebreathe), peripheral oxygen extraction (a-vO 2 -difference), and arterial stiffness (pulse wave velocity and augmentation index; tonometry). Data are presented as mean change and 95% CI. Results: 1-year of HIIT decreased body fat (-1.26%, CI: -2.43 to -0.58; p=0.036) and had a similar but less consistent effect on visceral fat (-0.28 kg, CI: -0.62 to 0.04; p=0.083). Aerobic capacity increased by ~24% (ΔVO 2 : 4.41 mL/kg/min, CI: 3.22 to 5.61; p&lt;0.0001), due to improved peak Q C (1.84 L/min, CI: 0.34 to 2.24; p=0.017) and a-vO 2 -difference (1.31 mL/100mL, CI: 0.13 to 2.49; p=0.031). While large elastic arterial stiffness was unchanged (PWV: -21 cm/s, CI: -61 to 19; p=0.299), augmentation index was reduced (-5.23%, CI: -9.18 to -1.35; p=0.009) indicative of improved ventricular-arterial coupling. There was no independent effect of PUFA, or interaction between HIIT and PUFA for any outcomes. Conclusions: 1-year HIIT improved leanness, aerobic fitness, peak Q C and a-vO 2 -difference, and ventricular-arterial coupling in middle-aged Stage A HFpEF. There was no independent or additive effect of PUFA administration. This is the first randomized trial to demonstrate that regular HIIT can reverse cardiometabolic impairments in Stage A HFpEF.